2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T6ca,Plasma cell leukemia (PCL) represents an exceptionally aggressive plasma cell malignancy defined by ≥5% circulating plasma cells in peripheral blood of patients otherwise meeting diagnostic criteria for multiple myeloma (MM), per International Myeloma Working Group consensus. This ultra-high-risk disease exhibits distinctive clinical features including frequent extramedullary involvement, severe cytopenias, hypercalcemia, renal insufficiency, and/or significantly elevated β2-microglobulin and lactate dehydrogenase levels. The molecular landscape includes high-risk cytogenetic abnormalities and mutations that promote accelerated proliferation, apoptotic resistance, immune evasion, and bone marrow microenvironmental independence through dysregulated adhesion molecule and chemokine receptor expression. While autologous stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies improved historical outcomes, the therapeutic paradigm continues to evolve. Novel therapeutic approaches including B-cell maturation antigen (BCMA)-directed therapies (bispecific antibodies and chimeric antigen receptor T-cell therapy), GPRC5D-targeted therapy, and BCL-2 inhibition demonstrate promise in treating both primary and secondary PCL. Despite these advances, PCL remains inadequately studied, with treatment approaches predominantly extrapolated from MM trials where PCL patients have largely been excluded. This review synthesizes current evidence and presents illustrative clinical cases demonstrating practical treatment approaches, while highlighting critical knowledge gaps requiring dedicated prospective clinical trials to meaningfully improve outcomes in this challenging disease entity.31:T6db,Plasma cell leukemia (PCL) represents an exceptionally aggressive plasma cell malignancy defined by ≥5% circulating plasma cells in peripheral blood of patients otherwise meeting diagnostic criteria for multiple myeloma (MM), per International Myeloma Working Group consensus. This ultra-high-risk disease exhibits distinctive clinical features including frequent extramedullary involvement, severe cytopenias, hypercalcemia, renal insufficiency, and/or significantly elevated β2-microglobulin and lactate dehydrogenase levels. The molecular landscape includes high-risk cytogenetic abnormalities and mutations that promote accelerated proliferation, apoptotic resistance, immune evasion, and bone marrow microenvironmental independence through dysregulated adhesion molecule and chemokine receptor expression. While autologous stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies improved historical outcomes, the therapeutic paradigm continues to evolve. Novel therapeutic approaches including B-cell maturation antigen (BCMA)-directed therapies (bispecific antibodies and chimeric antigen receptor T-cell therapy), GPRC5D-targeted therapy, and BCL-2 inhibition demonstrate promise in treating both primary and secondary PCL. Despite these advances, PCL remains inadequately studied, with treatment approaches predominantly extrapolated from MM trials where PCL patients have largely been excluded. This review synthesizes current evidence and presents illustrative clinical cases demonstrating practical treatment approaches, while highlighting critical knowledge gaps requiring dedicated prospective clinical trials to meaningfully improve outcomes in this challenging disease entity.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Proteasome Inhibitor: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Proteasome Inhibitor (modality). Clinician-written summaries and actionable practice insights. 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results in smaller subgroups (e.g., plasma cell leukaemia) may be underpowered.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00286-x","tag_type":"warning","value":"Subgroup analyses by high-risk features (≥2 HRCAs, high-risk GEP, plasma cell leukaemia) were post-hoc and should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00286-x","tag_type":"warning","value":"The ≥3 HRCAs subgroup did not appear to benefit, but exact numbers and CIs for this subgroup are not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1016/s1470-2045(26)00286-x","tag_type":"warning","value":"The external control (Myeloma XI) had a much longer median follow-up (~118 months) vs OPTIMUM (~71 months), which may affect OS comparisons as OPTIMUM OS data are still maturing.","value_numeric":null}],"summaries":{"what_studied":"The OPTIMUM/MUKnine phase 2 trial evaluated intensified induction (daratumumab + cyclophosphamide + bortezomib + lenalidomide + dexamethasone), extended consolidation, and maintenance after ASCT in 107 newly diagnosed high-risk multiple myeloma patients (≥2 HRCAs, high-risk GEP, or plasma cell leukaemia) at 22 UK centres, compared against 120 molecularly matched external controls from the Myeloma XI trial over a median 71-month follow-up.","key_result":"At 5-year follow-up, median PFS was not reached (NR) in OPTIMUM vs 24.4 months in controls (HR 0.32, 95% CI 0.22–0.45; p<0.0001); median OS was NR vs 57.4 months (HR 0.43, 95% CI 0.28–0.65; p<0.0001); median PFS2 was NR vs 43.9 months (HR 0.26, 95% CI 0.17–0.41; p<0.0001). Benefit was consistent across high-risk subgroups **except** patients with ≥3 HRCAs.","limitations":"- External control design (Myeloma XI) introduces potential confounding; groups were molecularly matched but not randomised.\n- Subgroup analyses (≥2 HRCAs, high-risk GEP, plasma cell leukaemia) were selected post-hoc.\n- No survival benefit demonstrated in the ≥3 HRCAs subgroup, suggesting a ceiling for this regimen in the highest-risk patients.","practice_takeaway":"For newly diagnosed high-risk myeloma defined by ≥2 cytogenetic abnormalities, high-risk GEP, or plasma cell leukaemia, an intensified daratumumab-based quadruplet regimen with extended consolidation and maintenance can more than double PFS and meaningfully extend OS. Molecular risk stratification at diagnosis is key to selecting patients most likely to benefit."}},{"doi":"10.1080/10428194.2026.2723847","pmid":"42702057","title":"MRD-guided induction-intensification with daratumumab–carfilzomib-based regimen followed by ASCT in patients with newly diagnosed multiple myeloma","journal_title":"Leukemia & Lymphoma","journal_issn":"1042-8194","published_at":"2026-09-06T00:00:00.000Z","url":"https://doi.org/10.1080/10428194.2026.2723847","source_score":5,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-11T06:20:08.418Z","updated_at":"2026-09-11T06:20:08.418Z","tags":[{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"brand","value":"Kyprolis","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"brand","value":"Revlimid","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"brand","value":"Velcade","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"generic","value":"carfilzomib","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"modality","value":"Anti-CD38 Antibody","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"modality","value":"Autologous Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"modality","value":"Immunomodulatory Agent","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"sample_size","value":"n=60","value_numeric":60},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"warning","value":"Follow-up of 28.5 months is relatively short for myeloma outcomes; PFS and OS estimates may change with longer observation.","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"warning","value":"MRD was assessed by multiparameter flow cytometry rather than next-generation sequencing; sensitivity threshold and comparability to other studies may differ.","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"warning","value":"Retrospective single-institution design with a small cohort (n=60) limits the strength of conclusions; results should be interpreted with caution pending prospective validation.","value_numeric":null},{"paper_doi":"10.1080/10428194.2026.2723847","tag_type":"warning","value":"The study does not clearly report patient age range or sex distribution, so age_group and sex tags are inferred from transplant-eligible NDMM context.","value_numeric":null}],"summaries":{"what_studied":"This single-institution retrospective study assessed an MRD-guided induction intensification strategy in 60 transplant-eligible newly diagnosed multiple myeloma (NDMM) patients treated between 2020–2025, where MRD-positive patients received daratumumab, carfilzomib, and dexamethasone intensification before ASCT.","key_result":"Among 52 evaluable patients, 67.3% (35/52) achieved MRD negativity pre-ASCT and 93.8% (30/32) post-ASCT; at median 28.5 months follow-up, 2-year PFS was 87.3% and OS was 98.0%. R-ISS stage III, extramedullary disease, and high-risk cytogenetics were associated with worse PFS.","limitations":"Single-institution retrospective design with only 60 patients limits generalizability; short median follow-up of 28.5 months may not capture late relapses; MRD assessment used multiparameter flow cytometry rather than next-generation sequencing, which may affect sensitivity.","practice_takeaway":"An MRD-guided intensification approach with daratumumab-carfilzomib before ASCT is feasible and achieves deep responses without compromising stem cell mobilization, but clinicians should consider additional post-transplant strategies for patients with high-risk cytogenetics, R-ISS III, or extramedullary disease."}},{"doi":"10.1016/j.jinf.2026.106840","pmid":"42700823","title":"Risk Stratification for Tuberculosis Reactivation in Patients Receiving Biological and Non-biological Immunomodulators: A Review of Current Literature","journal_title":"Journal of Infection","journal_issn":"0163-4453","published_at":"2026-09-06T00:00:00.000Z","url":"https://doi.org/10.1016/j.jinf.2026.106840","source_score":40,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-09T06:21:07.655Z","updated_at":"2026-09-09T06:21:07.655Z","tags":[{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"category","value":"Infectious Diseases","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"condition","value":"Latent Tuberculosis Infection","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"condition","value":"Tuberculosis","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"BCL-2 Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Biologic Immunomodulator","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Calcineurin Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Glucocorticoid","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Integrin Antagonist","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Interleukin Antagonist","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"JAK Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.jinf.2026.106840","tag_type":"warning","value":"No sample size is applicable — this is a review article with no primary patient cohort. Impact flag 'practice_changing' applied because the review consolidates FDA/EMA regulatory guidance across nine drug classes into a single actionable framework, which is clinically significant; however, it is based on synthesized rather than new trial evidence. Sex of study population is not reported, as expected for a literature review.","value_numeric":null}],"summaries":{"what_studied":"This narrative review synthesizes current evidence on latent tuberculosis infection (LTBI) reactivation mechanisms and risk levels associated with nine major classes of immunosuppressive agents (biological and non-biological), and collates FDA and EMA prescribing guidance on TB screening across these drug classes.","key_result":"Multiple immunosuppressant classes — including B- and T-cell depleting agents, interleukin antagonists, cytokine antagonists, integrin antagonists, immune checkpoint inhibitors, kinase inhibitors, proteasome inhibitors, calcineurin inhibitors, glucocorticoids, and BCL-2 inhibitors — carry meaningful risk of LTBI reactivation, underscoring the need for systematic TB screening and preventive therapy before initiation.","limitations":"As a narrative review, it does not perform a meta-analysis or quantify comparative reactivation rates across drug classes; risk estimates depend on the quality and heterogeneity of the underlying primary literature. No original patient-level data are presented.","practice_takeaway":"Before starting any major immunosuppressive agent, screen patients for LTBI using both tuberculin skin test and IGRA, and initiate preventive treatment per FDA/EMA guidance — especially for TNF antagonists, JAK inhibitors, and T/B-cell depleting therapies, which carry the highest reactivation concern. Maintain vigilance for TB reactivation throughout the treatment course, even in patients who screened negative at baseline."}},{"doi":"10.1002/ajh.70475","pmid":"42613778","title":"Multiple Myeloma: 2026 Update on Diagnosis, Risk‐Stratification and Management","journal_title":"American Journal of Hematology","journal_issn":"0361-8609","published_at":"2026-08-18T00:00:00.000Z","url":"https://doi.org/10.1002/ajh.70475","source_score":88,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-24T06:18:14.674Z","updated_at":"2026-08-24T06:18:14.674Z","tags":[{"paper_doi":"10.1002/ajh.70475","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"brand","value":"Sarclisa","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"condition","value":"Smoldering Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"generic","value":"belantamab mafadotin","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"generic","value":"isatuximab","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"Autologous Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"study_design","value":"Narrative Review / Clinical Practice Update","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"warning","value":"Brand name 'Darzalex' listed for daratumumab; isatuximab brand 'Sarclisa' inferred from common knowledge — not explicitly stated in the abstract.","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"warning","value":"The label 'practice_changing' reflects major updates to both risk stratification criteria and frontline quadruplet therapy recommendations.","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"warning","value":"The paper was published August 18, 2026, just 6 days before today's date; some referenced trials or approvals may be very recent and not yet widely implemented.","value_numeric":null},{"paper_doi":"10.1002/ajh.70475","tag_type":"warning","value":"This is a guideline/review article, not a primary trial — level of evidence reflects expert synthesis, not a controlled study. No sample size is applicable.","value_numeric":null}],"summaries":{"what_studied":"A comprehensive 2026 update on the diagnosis, risk-stratification, and management of multiple myeloma (MM), covering criteria for MM-defining events, high-risk cytogenetic definitions, frontline quadruplet regimens, maintenance strategies, and relapsed/refractory options.","key_result":"Frontline standard-of-care is now a quadruplet (anti-CD38 + bortezomib/lenalidomide/dexamethasone) followed by ASCT in eligible patients; high-risk MM is redefined to include bi-allelic del(1p), combination cytogenetic lesions with gain(1q) or del(1p), and p53 mutation; daratumumab for 3 years is recommended for high-risk smoldering MM.","limitations":"This is a narrative review/guideline update, not a primary clinical trial — it synthesizes existing evidence without new original data or formal meta-analysis.","practice_takeaway":"Upgrade frontline-eligible patients to anti-CD38–based quadruplet therapy (Dara- or Isa-VRd) and reassess high-risk status using the expanded cytogenetic criteria including gain(1q)/del(1p) combinations. For high-risk smoldering MM, consider 3 years of daratumumab to delay progression."}},{"doi":"10.1111/bjh.70697","pmid":"42543782","title":"High prevalence of iron deficiency among daratumumab‐treated newly diagnosed multiple myeloma patients","journal_title":"British Journal of Haematology","journal_issn":"0007-1048","published_at":"2026-08-02T00:00:00.000Z","url":"http://dx.doi.org/10.1182/blood-2023-184607","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-05T13:22:59.476Z","updated_at":"2026-08-05T13:22:59.476Z","tags":[{"paper_doi":"10.1111/bjh.70697","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"brand","value":"Ninlaro","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"brand","value":"Revlimid","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"brand","value":"Velcade","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"condition","value":"Anemia","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"condition","value":"Iron Deficiency","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"generic","value":"ixazomib","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"sample_size","value":"n=75","value_numeric":75},{"paper_doi":"10.1111/bjh.70697","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"study_design","value":"Retrospective Case-Control Study","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"warning","value":"Iron deficiency was defined solely by ferritin <30 mcg/L; functional iron deficiency (e.g., transferrin saturation) was not reported, potentially underestimating the true burden.","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"warning","value":"Sample sizes are small and unequal (55 vs. 20), limiting generalizability and statistical power.","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"warning","value":"The case and control groups received different regimens (Dara-IRD vs. VRD), so differences in iron status may reflect regimen-specific effects beyond daratumumab alone — confounding cannot be excluded.","value_numeric":null},{"paper_doi":"10.1111/bjh.70697","tag_type":"warning","value":"The two DOIs in the metadata (bjh.70697 and blood-2023-184607) may refer to different publications; the blood-2023 DOI may be a related conference abstract rather than the primary source.","value_numeric":null}],"summaries":{"what_studied":"This retrospective case-control study evaluated the prevalence of iron deficiency (ID) in newly diagnosed multiple myeloma (NDMM) patients treated with daratumumab, ixazomib, lenalidomide, and dexamethasone (Dara-IRD; n=55) versus an age- and sex-matched cohort treated with bortezomib, lenalidomide, and dexamethasone (VRD; n=20) over 1 year.","key_result":"At 1 year, ~50% of Dara-IRD patients met criteria for iron deficiency (ferritin <30 mcg/L) vs. 0% of VRD controls; 100% of Dara-IRD patients had a ferritin decline from baseline vs. 45% in the VRD group.","limitations":"Retrospective design with a small, unequal sample size (n=55 vs. n=20) limits statistical power; study cannot establish causality or fully exclude confounding from regimen differences; ID was defined by ferritin alone, which may not capture functional iron deficiency.","practice_takeaway":"Clinicians should routinely monitor iron status (ferritin) in NDMM patients receiving daratumumab-based regimens, as ID developed in nearly half of patients within 1 year. Early identification may allow timely iron supplementation to address a potentially modifiable contributor to anaemia."}},{"doi":"10.1182/blood.2026033241","pmid":"42526890","title":"A first-in-class RNA degrader reduces c-MYC expression and myeloma cell survival in preclinical models","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-07-29T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2026033241","source_score":12,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-06T13:22:14.809Z","updated_at":"2026-08-06T13:22:14.809Z","tags":[{"paper_doi":"10.1182/blood.2026033241","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"brand","value":"Kyprolis","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"brand","value":"Pomalyst","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"brand","value":"Revlimid","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"generic","value":"carfilzomib","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"generic","value":"pomalidomide","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"modality","value":"RiboTAC","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"modality","value":"RNA Degrader","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"study_design","value":"Preclinical Study","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"warning","value":"Publication date is July 2026; this is a very recent paper and has not yet undergone post-publication peer scrutiny.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"warning","value":"Sample size (number of patient samples and cell lines) is not specified in the abstract; total N is indeterminate.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"warning","value":"Study design is classified as 'Preclinical Study'; it combines in vitro and in vivo (mouse) work without a single canonical label.","value_numeric":null},{"paper_doi":"10.1182/blood.2026033241","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the novelty of the RNA-degrader mechanism rather than clinical evidence, as all data are preclinical; no human trials are reported.","value_numeric":null}],"summaries":{"what_studied":"A ribonuclease-targeting chimera (RiboTAC) designed to degrade MYC mRNA was evaluated for anti-myeloma activity across primary patient MM samples, MM cell lines, and NOD SCID xenograft mouse models, including assessment of synergy with carfilzomib, lenalidomide, and pomalidomide.","key_result":"MYC-RiboTAC reduced MYC mRNA and protein in an RNase L-dependent manner, suppressed growth in MYC/RNase L co-expressing MM cells even in a protective bone marrow microenvironment, and significantly inhibited tumor growth in two MM xenograft models with favorable safety and PK profiles in mice.","limitations":"Findings are preclinical only (cell lines, primary samples, and mouse xenografts); no human pharmacokinetic or safety data; efficacy requires co-expression of both MYC and RNase L, which may limit applicability in tumors with low RNase L levels.","practice_takeaway":"MYC-RiboTAC represents a novel RNA-degrader approach to targeting the 'undruggable' MYC oncogene in multiple myeloma; while still preclinical, its synergy with carfilzomib and IMiDs and bone marrow-penetrant activity make it a candidate to watch for future clinical translation."}},{"doi":"10.1182/bloodadvances.2025018896","pmid":"42418393","title":"Maintenance therapy and improved relapse-free survival in patients with monoclonal gammopathy of renal significance","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2025018896","source_score":14,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-06T06:23:11.810Z","updated_at":"2026-09-06T06:23:11.810Z","tags":[{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"condition","value":"Monoclonal Gammopathy of Renal Significance","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"condition","value":"Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"modality","value":"Anti-CD38 Antibody","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"modality","value":"Autologous Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"modality","value":"Immunomodulatory Agent","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"sample_size","value":"n=50","value_numeric":50},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"warning","value":"Maintenance therapy details (agent type, duration) are not fully specified in the available text, limiting direct clinical translation.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"warning","value":"Sex breakdown of the cohort is not explicitly reported in the abstract or full text provided.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — findings are hypothesis-generating given the small, retrospective sample and lack of a randomized control group.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025018896","tag_type":"warning","value":"The wide confidence intervals in the multivariate OS analysis (e.g., HR 21.39; 95% CI 1.94–2915.45) reflect very small event counts and should be interpreted with caution.","value_numeric":null}],"summaries":{"what_studied":"Retrospective analysis of 50 biopsy-proven MGRS patients across 3 institutions, evaluating plasma cell (PC)-directed vs. B-cell-directed therapy, induction regimen, ASCT use, maintenance therapy, and induction duration on relapse-free survival (RFS) and overall survival (OS) over a median follow-up of 6.15 years.","key_result":"Among PC-treated patients (n=37), maintenance therapy was associated with an 87% reduction in relapse risk (HR 0.13; 95% CI 0.03–0.53; p=0.004) on multivariate analysis; induction duration ≥6 months also independently improved RFS (HR 0.21; 95% CI 0.06–0.68; p=0.009). Median RFS was 3.74 years in the PC group vs. 19 years in the B-cell group. No significant RFS or OS differences were found by induction regimen type or ASCT use.","limitations":"- Small retrospective cohort (n=50) from 3 institutions limits generalizability and statistical power.\n- Maintenance therapy group (n=13/37) is particularly small, increasing risk of confounding despite multivariate adjustment.\n- Heterogeneous MGRS histopathologies (72% PGNMID) and varied treatment regimens preclude definitive regimen-specific conclusions.","practice_takeaway":"Consider maintenance therapy and prolonged induction (≥6 months) in PC-driven MGRS to reduce relapse risk—these factors independently improved RFS even after adjustment for age and induction duration. Choice of induction regimen (including daratumumab-based) or ASCT did not significantly affect outcomes in this cohort."}},{"doi":"10.1038/s41408-026-01542-7","pmid":"42399235","title":"Response profile and long-term outcomes in Cyclin D1-overexpressing multiple myeloma: insights from the CASSIOPEIA trial","journal_title":"Blood Cancer Journal","journal_issn":"2044-5385","published_at":"2026-07-03T00:00:00.000Z","url":"https://doi.org/10.1038/s41408-026-01542-7","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-07T13:26:13.130Z","updated_at":"2026-07-07T13:26:13.130Z","tags":[{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"generic","value":"thalidomide","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"modality","value":"Autologous Stem Cell Transplant","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"sample_size","value":"n=589","value_numeric":589},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"study_design","value":"Post-hoc Subgroup Analysis of Phase 3 Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"warning","value":"The CCND1 overexpression RNA signature is used as a surrogate for t(11;14) but was not validated against FISH or cytogenetics in this dataset; some patients in each group may be misclassified.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"warning","value":"The study design tag reflects the nature of this analysis as a post-hoc subgroup investigation within a phase 3 RCT, not a prospectively designed substudy.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01542-7","tag_type":"warning","value":"This is a post-hoc analysis of the CASSIOPEIA trial and was not a pre-specified endpoint; results should be interpreted with caution regarding causality.","value_numeric":null}],"summaries":{"what_studied":"This analysis of the phase 3 CASSIOPEIA trial examined whether a CCND1 overexpression RNA signature (a surrogate for t(11;14), n=164 of 589 patients, 27.8%) was associated with MRD negativity rates and long-term outcomes (PFS, OS) over a median follow-up of >7 years in transplant-eligible newly diagnosed multiple myeloma treated with VTD ± daratumumab.","key_result":"CCND1-overexpressing patients had markedly lower MRD negativity after induction (20.9% vs. 50.8%, p<0.0001) and after transplant/consolidation (59.1% vs. 78.2%, p<0.0001), yet PFS (p=0.733) and OS (p=0.967) were indistinguishable from patients without CCND1 overexpression.","limitations":"- CCND1 RNA overexpression is not a perfect surrogate for t(11;14); the translocation was not systematically assessed in this trial.\n- Analysis is a post-hoc subgroup analysis of a trial not designed to test this hypothesis.\n- Findings are specific to VTD/D-VTD regimens; generalizability to lenalidomide- or isatuximab-based quadruplets is uncertain.","practice_takeaway":"In transplant-eligible newly diagnosed myeloma, patients with CCND1 overexpression (t(11;14)) respond more slowly and achieve lower MRD negativity rates, but their long-term survival is no worse — so clinicians should avoid escalating therapy based on MRD results alone in this subgroup. Genetic characterization and MRD should be interpreted together, recognizing that standard MRD thresholds may overestimate risk in this genetically distinct group."}},{"doi":"10.1038/s41408-026-01550-7","pmid":"42393044","title":"Expression profile of CASSIOPEIA patients refines prognostic value of MRD negativity in multiple myeloma","journal_title":"Blood Cancer Journal","journal_issn":"2044-5385","published_at":"2026-07-02T00:00:00.000Z","url":"https://doi.org/10.1038/s41408-026-01550-7","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-07T13:26:13.557Z","updated_at":"2026-07-07T13:26:13.557Z","tags":[{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"generic","value":"thalidomide","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"sample_size","value":"n=628","value_numeric":628},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"study_design","value":"Translational Substudy of Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"warning","value":"Full text was not available; summary is based on the abstract and publisher page only.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"warning","value":"Study design tag reflects a transcriptomic subset analysis nested within the CASSIOPEIA RCT — not a standalone RCT; level of evidence assigned accordingly.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"warning","value":"The manuscript was in pre-final (unedited) form at publication; some details may change in the final version.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01550-7","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously: findings are hypothesis-generating and require prospective validation before altering standard MRD-guided clinical practice.","value_numeric":null}],"summaries":{"what_studied":"This study used RNA sequencing and consensus clustering to define transcriptomic subgroups in 628 transplant-eligible newly diagnosed multiple myeloma (NDMM) patients from the CASSIOPEIA trial (daratumumab ± bortezomib/thalidomide/dexamethasone ± maintenance), then evaluated how these subgroups interact with post-consolidation MRD negativity to refine risk prediction over 72 months.","key_result":"Five MM subtypes were identified and grouped into three transcriptomic risk categories with 72-month PFS rates of 70% (low), 51% (intermediate), and 27% (high) in daratumumab-treated patients. MRD negativity rates were paradoxically higher in high-risk vs. intermediate patients, yet its prognostic impact was significantly reduced in the high-risk group, suggesting MRD negativity alone does not adequately predict outcomes in these patients.","limitations":"This is a subset analysis (n=628 of the full CASSIOPEIA cohort), which may limit generalizability. The study is exploratory/retrospective in design within a prospective trial, and full manuscript text was not yet available at extraction (pre-final publication version).","practice_takeaway":"For high-risk MM patients (by transcriptomic profiling), achieving MRD negativity after consolidation should not be interpreted as reassuring in the same way as for low-risk patients — these patients likely need additional or novel therapeutic strategies beyond standard MRD-guided decisions. Baseline molecular profiling should be integrated alongside MRD assessment to better stratify prognosis."}},{"doi":"10.1038/s41409-026-02955-5","pmid":"42387202","title":"Impact of doublet post-transplant maintenance on outcomes in multiple myeloma: A propensity score matching analysis","journal_title":"Bone Marrow Transplantation","journal_issn":"0268-3369","published_at":"2026-07-01T00:00:00.000Z","url":"https://doi.org/10.1038/s41409-026-02955-5","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-05T13:38:37.395Z","updated_at":"2026-07-05T13:38:37.395Z","tags":[{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"modality","value":"Autologous Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"sample_size","value":"n=410","value_numeric":410},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"warning","value":"High-risk disease subgroup results are referenced qualitatively but specific subgroup HR data are not provided in the abstract.","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"warning","value":"Propensity score matching reduces but does not eliminate confounding; residual selection bias is possible given the significant size imbalance between groups (n=80 doublet vs. n=330 monotherapy).","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously — this is a single-center retrospective study with PSM; prospective RCT-level confirmation is still needed.","value_numeric":null},{"paper_doi":"10.1038/s41409-026-02955-5","tag_type":"warning","value":"The paper does not report specific follow-up duration or median EFS/OS times, limiting absolute survival estimates.","value_numeric":null}],"summaries":{"what_studied":"Single-center retrospective study of 410 MM patients who underwent ASCT (2015–2023) comparing doublet post-transplant maintenance (≥2 agents, n=80) vs. monotherapy (single agent, n=330), using propensity score matching to control for treatment allocation bias; primary outcomes were EFS and OS.","key_result":"In the PSM analysis, doublet maintenance was associated with significantly better EFS (aHR 0.48, p=0.007) and OS (aHR 0.47, p=0.029) compared to monotherapy. The most common doublet was bortezomib-lenalidomide (58%); most common monotherapy was lenalidomide (48%).","limitations":"Single-center retrospective design limits generalizability; doublet group was much smaller (n=80 vs. n=330), raising potential residual confounding despite PSM; dexamethasone exclusion from maintenance definitions may affect cross-study comparisons.","practice_takeaway":"Doublet maintenance (especially bortezomib-lenalidomide) after ASCT was associated with nearly half the risk of progression/death compared to monotherapy in this real-world cohort. Clinicians should consider doublet maintenance more broadly, particularly for high-risk MM patients, while awaiting larger prospective confirmation."}},{"doi":"10.1182/bloodadvances.2026019699","pmid":null,"title":"Targeting BCMA in patients with relapsed/refractory multiple myeloma in 1 to 3 prior lines of therapy","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-06-03T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2026019699","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":false,"crossref":true,"unpaywall":true},"created_at":"2026-07-21T13:34:42.449Z","updated_at":"2026-07-21T13:34:42.449Z","tags":[{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"carfilzomib","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"elotuzumab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"isatuximab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"generic","value":"pomalidomide","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"modality","value":"Antibody-Drug Conjugate","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"modality","value":"Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"modality","value":"Immunomodulatory Agent","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"warning","value":"Sample size tag is not applied as this is a review article aggregating multiple trials rather than a single-study population.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"warning","value":"Study design classified as 'Narrative Review'; the paper references phase 3 trials but does not itself conduct a systematic review or meta-analysis.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026019699","tag_type":"warning","value":"This paper is a narrative review and synthesizes legacy triplet trial data alongside emerging BCMA-directed therapy; no new primary efficacy data are reported. The full text provided is primarily a supplemental table of legacy trials, so specific details on BCMA-directed trial results (CAR-T, bispecifics, ADCs) mentioned in the abstract are not available in the extracted text.","value_numeric":null}],"summaries":{"what_studied":"This review synthesizes data from phase 3 trials of BCMA-directed therapies (CAR-T cells, bispecific antibodies, and antibody-drug conjugates) in relapsed/refractory multiple myeloma (RRMM) patients with 1–3 prior lines of therapy, alongside legacy triplet regimens (PI/IMiD, anti-SLAMF7, anti-CD38 combinations).","key_result":"Legacy phase 3 triplet trials showed median PFS ranging from 10.3 months (EPd) to 44.5 months (DRd), with OS HRs favoring experimental arms across most regimens; the review frames these as a backdrop for emerging BCMA-directed therapy decision-making in the early-relapse setting.","limitations":"This is a narrative review without meta-analysis; cross-trial comparisons are limited by heterogeneous patient populations, trial designs, and prior treatment exposure. Real-world applicability and access barriers to newer BCMA therapies are noted but not quantified.","practice_takeaway":"When selecting therapy for RRMM after 1–3 prior lines, clinicians should weigh patient age, fitness, comorbidities, prior treatment exposure (especially lenalidomide and anti-CD38), and access to BCMA-directed therapies. Shared decision-making is essential given the expanding but logistically complex options."}},{"doi":"10.1200/jco-26-00755","pmid":"42212672","title":"Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1200/jco-26-00755","source_score":55,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-16T13:37:22.248Z","updated_at":"2026-07-16T13:37:22.248Z","tags":[{"paper_doi":"10.1200/jco-26-00755","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"condition","value":"Cardiac Amyloidosis","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"condition","value":"Immunoglobulin Light Chain Amyloidosis","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"generic","value":"anselamimab","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"modality","value":"Anti-Amyloid Fibril Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"modality","value":"CD38-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"sample_size","value":"n=406","value_numeric":406},{"paper_doi":"10.1200/jco-26-00755","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"warning","value":"Baseline imbalance in the kappa subgroup (higher stage IIIb and NT-proBNP in the anselamimab arm) could bias survival results in favor of placebo, making the observed HR of 0.38 potentially conservative but also less certain.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"warning","value":"Several authors are employees or stockholders of Alexion/AstraZeneca, the study sponsor; industry involvement should be considered when interpreting results.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"warning","value":"The kappa isotype benefit is a prespecified subgroup analysis but was not powered for formal hypothesis testing; nominal P-values should be interpreted cautiously without multiplicity adjustment.","value_numeric":null},{"paper_doi":"10.1200/jco-26-00755","tag_type":"warning","value":"The primary endpoint was amended mid-trial (from time-to-ACM to a hierarchical composite) due to improved background therapies; this protocol change may affect interpretation of results.","value_numeric":null}],"summaries":{"what_studied":"Two parallel phase III double-blind RCTs (CARES; CAEL101-301 and CAEL101-302) evaluated anselamimab (1,000 mg/m²) vs. placebo added to CyBorD ± daratumumab in 406 newly diagnosed adults with Mayo stage IIIa or IIIb AL amyloidosis, analyzed over 18 months after last enrollment. The primary endpoint was a hierarchical composite of all-cause mortality (ACM) and cardiovascular hospitalizations (CVH) using the Finkelstein-Schoenfeld test.","key_result":"The primary endpoint was **not met** overall (win ratio 1.11; 95% CI 0.83–1.50; P=.332). In the **kappa isotype subgroup** (n=72, ~18% of patients), anselamimab reduced ACM by 62% (HR 0.38; 95% CI 0.17–0.86; P=.012) and CVH by 71% (IRR 0.29; 95% CI 0.10–0.87; P=.028), with a composite win ratio of 2.06 (95% CI 0.98–4.31). **No benefit** was seen in the lambda isotype population (HR 1.02; P=.647). Safety was comparable between arms overall.","limitations":"- The kappa subgroup (n=72) was small and underpowered for the hierarchical Finkelstein-Schoenfeld test, which requires larger samples; kappa findings are nominally significant but not formally controlled for multiplicity.\n- Imbalance within the kappa subgroup at baseline: more anselamimab-treated patients were in stage IIIb with higher NT-proBNP levels, which could confound survival comparisons.\n- The primary endpoint and analysis plan were amended mid-trial due to improved background therapies reducing mortality events, introducing potential for bias.","practice_takeaway":"Do not use anselamimab broadly in AL amyloidosis — it did not meet its primary endpoint in the overall population. However, clinicians treating newly diagnosed **kappa-isotype** AL amyloidosis (identifiable at diagnosis with standard tests) should be aware of the striking ACM and CVH reductions observed; confirmatory trials restricted to this subgroup are needed before routine use."}},{"doi":"10.1038/s41593-026-02297-x","pmid":"42215643","title":"Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner","journal_title":"Nature Neuroscience","journal_issn":"1097-6256","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1038/s41593-026-02297-x","source_score":69,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:30.600Z","updated_at":"2026-06-03T13:44:30.600Z","tags":[{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"category","value":"Neurosciences","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"condition","value":"Alzheimer's Disease","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"condition","value":"Tauopathy","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"generic","value":"apolipoprotein E4","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"modality","value":"Gene Knock-In Model","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"study_design","value":"Preclinical Experimental Study (Primary Neurons and Transgenic Mice)","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"warning","value":"No specific sample size (total N) was consistently reported in the available text; the sample_size tag was omitted accordingly.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"warning","value":"'practice_changing' impact flag applied cautiously: the mechanistic novelty (neuroproteasome–APOE–tau axis) is high, but all evidence is preclinical with no direct clinical translation yet demonstrated.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"warning","value":"Study design label reflects a basic/mechanistic preclinical study; it does not fit standard clinical trial design categories.","value_numeric":null},{"paper_doi":"10.1038/s41593-026-02297-x","tag_type":"warning","value":"The full paper text was not available—only the abstract and reporting summary were provided; numerical details on effect sizes, exact N values, and specific statistical outcomes could not be extracted.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether neuron-specific plasma membrane proteasomes ('neuroproteasomes') regulate endogenous tau paired helical filament (PHF) formation, and whether this process is modulated by APOE genotype (E2, E3, E4) and age, using primary neurons and mouse brain models.","key_result":"Selective neuroproteasome inhibition triggered de novo formation of sarkosyl-insoluble endogenous tau PHFs in primary neurons and mouse brain, biochemically and ultrastructurally matching human AD PHFs. Neuroproteasome plasma membrane abundance followed an E2 > E3 > E4 hierarchy and declined with age; ApoE4 neurons aggregated tau with modest disruption while ApoE2 neurons were resistant.","limitations":"Sample sizes were not predetermined; most in vivo experiments were limited by transgenic animal availability (minimum 3 male + 3 female mice). Primary neuron cultures were mixed sex without individual sex determination. Blinding was inconsistent—investigators performing cell culture experiments were rarely blinded except in replication studies.","practice_takeaway":"These findings position the neuroproteasome as a node linking APOE4 risk and aging to tau pathology, suggesting it may be a future therapeutic target—though all data are preclinical and no drug interventions for patients are yet implied."}},{"doi":"10.3324/haematol.2026.300897","pmid":"42206445","title":"A phase I/II study of twice-weekly ixazomib plus pomalidomide and dexamethasone in relapsed and refractory multiple myeloma","journal_title":"Haematologica","journal_issn":"1592-8721","published_at":"2026-05-28T00:00:00.000Z","url":"https://doi.org/10.3324/haematol.2026.300897","source_score":6,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-02T13:27:32.659Z","updated_at":"2026-06-02T13:27:32.659Z","tags":[{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"brand","value":"Ninlaro","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"brand","value":"Pomalyst","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"condition","value":"Relapsed/Refractory Multiple Myeloma","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"generic","value":"ixazomib","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"generic","value":"pomalidomide","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"modality","value":"Corticosteroid","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"sample_size","value":"n=50","value_numeric":50},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"study_design","value":"Phase I/II Clinical Trial","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"warning","value":"Brand name 'Ninlaro' is the canonical brand for ixazomib; confirmation of brand applicability in this study's context was inferred from the generic.","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"warning","value":"Full text pages beyond the abstract were not extractable from the PDF, so details on patient demographics, subgroup analyses, and secondary endpoints are drawn solely from the abstract.","value_numeric":null},{"paper_doi":"10.3324/haematol.2026.300897","tag_type":"warning","value":"The level of evidence is assigned as 2 given the prospective phase I/II design, but the non-randomized single-arm nature limits direct comparisons.","value_numeric":null}],"summaries":{"what_studied":"This phase I/II dose-escalation and expansion study evaluated twice-weekly oral ixazomib (3 or 4 mg, days 1/4/8/11) plus pomalidomide (2–4 mg, days 1–14) and dexamethasone (8 or 12 mg) in 21-day cycles in 50 patients with relapsed/refractory multiple myeloma (RRMM) who had received a median of 2 prior lines of therapy (98% prior lenalidomide, 88% prior bortezomib).","key_result":"The overall response rate was 60.0% (≥VGPR in 24.0%) across all 50 patients, and 65.8% (≥VGPR in 28.9%) in the 38 patients treated at the recommended phase II dose (ixazomib 4 mg + pomalidomide 4 mg); median duration of response was 18.0 and 19.3 months, median PFS was 13.9 and 17.8 months, and 3-year OS rates were 85.2% and 80.3%, respectively.","limitations":"- Single-arm, non-randomized design limits comparative efficacy conclusions.\n- Small sample size (n=50 total; n=38 at RP2D) reduces statistical power.\n- Most patients were lenalidomide- and bortezomib-pretreated but the degree of refractoriness (vs. relapse) to prior agents is not fully detailed in the abstract.","practice_takeaway":"Twice-weekly all-oral ixazomib + pomalidomide + dexamethasone achieved a ~66% response rate with a median PFS of ~18 months at the RP2D, offering a convenient, well-tolerated option for RRMM patients who have progressed on lenalidomide and bortezomib. Clinicians should monitor for neutropenia (grade 3/4 in ~26%) and thrombocytopenia (grade 3/4 in ~16%), which were the most common serious toxicities."}},{"doi":"10.1053/j.ajkd.2026.01.011","pmid":"42167833","title":"Malignancy and Kidney Transplant: Core Curriculum 2026","journal_title":"American Journal of Kidney Diseases","journal_issn":"0272-6386","published_at":"2026-05-20T00:00:00.000Z","url":"https://doi.org/10.1053/j.ajkd.2026.01.011","source_score":24,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:31.911Z","updated_at":"2026-06-03T13:44:31.911Z","tags":[{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"brand","value":"Opdivo","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"AL Amyloidosis","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Cutaneous Squamous Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Kidney Transplantation","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Melanoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Merkel Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Plasma Cell Dyscrasia","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Posttransplant Lymphoproliferative Disorder","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"condition","value":"Renal Cell Carcinoma","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"acitretin","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"azathioprine","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"belzutifan","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"cemiplimab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"ipilimumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"mycophenolate mofetil","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"nivolumab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"sirolimus","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"generic","value":"tacrolimus","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Calcineurin Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Immune Checkpoint Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"mTOR Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Oncolytic Virus Therapy","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"modality","value":"Tyrosine Kinase Inhibitor","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"study_design","value":"Review Article / Core Curriculum","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"Emerging therapies (oncolytic virus, EBV-VST, CAR-T in transplant) are discussed based on early-phase or limited case data and should not be considered standard of care.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"ICI rejection risk figures (25–42%) are pooled from retrospective cohorts with heterogeneous IS reduction practices, limiting direct applicability.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"Sample size tag omitted as no single study population is defined across this multi-topic review.","value_numeric":null},{"paper_doi":"10.1053/j.ajkd.2026.01.011","tag_type":"warning","value":"This is a narrative Core Curriculum review, not a primary research study; evidence grades vary widely by topic and most recommendations are expert consensus or based on observational data.","value_numeric":null}],"summaries":{"what_studied":"This Core Curriculum reviews cancer risk, screening, and management in kidney transplant candidates and recipients (KTRs), covering skin cancers, PTLD, plasma cell dyscrasias, and solid tumors, with emphasis on immunosuppression (IS) management and emerging therapies including immune checkpoint inhibitors (ICIs) and CAR-T cells.","key_result":"KTRs face 2–4× higher overall cancer risk vs. the general population; skin cancer SIRs reach 65–250 (cSCC) and 13–24 (Merkel cell); DLBCL is 8× more common; kidney cancer is 7× more common. ICI use carries ~25–42% acute rejection risk; patients on corticosteroids + mTOR inhibitors had lower rejection (HR 0.30). Median overall survival after transplant was 8.4 years for myeloma and 8.6 years for AL amyloidosis KTRs.","limitations":"Most recommendations are based on expert consensus, observational data, and case series rather than RCTs; ICI safety/efficacy data in KTRs come largely from retrospective analyses; screening benefit on long-term mortality in KTRs remains unproven.","practice_takeaway":"Convert azathioprine to mycophenolate or switch to an mTOR inhibitor for KTRs with recurrent non-melanoma skin cancers; minimize IS (remove antimetabolites first) when initiating ICI, and treat ICI-associated rejection with pulse steroids rather than antithymocyte globulin to preserve antitumor response. Cervical cancer screening should be more frequent (every 6–12 months) after transplant, and IMiDs should be stopped ≥4 weeks before kidney transplant in myeloma patients."}},{"doi":"10.1002/ajh.70373","pmid":"42138287","title":"Plasmablastic Lymphoma: 2026 Update on Diagnosis, Risk Stratification, and Management","journal_title":"American Journal of Hematology","journal_issn":"0361-8609","published_at":"2026-05-15T00:00:00.000Z","url":"https://doi.org/10.1002/ajh.70373","source_score":15,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-20T13:23:21.725Z","updated_at":"2026-05-20T13:23:21.725Z","tags":[{"paper_doi":"10.1002/ajh.70373","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"brand","value":"Velcade","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"condition","value":"HIV-Associated Lymphoma","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"condition","value":"Plasmablastic Lymphoma","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"modality","value":"BCMA-Targeted Therapy","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"modality","value":"Combination Chemotherapy","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"warning","value":"Brand name tags (Velcade, Darzalex) are inferred from the generics mentioned; the abstract does not explicitly list brand names.","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"warning","value":"EPOCH regimen referenced without specifying dose-adjusted (DA-EPOCH) vs. standard infusional EPOCH; clinicians should verify the specific protocol in the full text.","value_numeric":null},{"paper_doi":"10.1002/ajh.70373","tag_type":"warning","value":"This is a 2026 narrative update/review article, not a primary clinical study — no new patient-level data or trial results are presented. Evidence quality for specific treatment recommendations could not be independently graded from the abstract alone.","value_numeric":null}],"summaries":{"what_studied":"A 2026 narrative update on plasmablastic lymphoma (PBL) covering diagnosis, risk stratification, and management strategies — including chemotherapy regimens, novel agents, and targeted therapies — across HIV-positive, immunosuppressed, and immunocompetent populations.","key_result":"Infusional EPOCH is the recommended backbone chemotherapy; adding bortezomib or daratumumab may improve outcomes. BCMA-targeted therapies show early efficacy. Poor prognostic factors include age ≥ 60, advanced stage, and high IPI scores.","limitations":"As a narrative update (not a primary study), no new trial data or patient-level outcomes are reported. Evidence base for novel agents (bortezomib, daratumumab, BCMA-targeted therapy) remains limited to early/preliminary data. No head-to-head comparisons between regimens are provided.","practice_takeaway":"For PBL, use infusional EPOCH as the chemotherapy backbone and consider adding bortezomib or daratumumab to improve outcomes. Enroll eligible patients in prospective clinical trials, as the evidence base for this rare lymphoma remains thin."}},{"doi":"10.1182/blood.2025032099","pmid":"42118698","title":"Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025032099","source_score":16,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:39.924Z","updated_at":"2026-05-18T13:25:39.924Z","tags":[{"paper_doi":"10.1182/blood.2025032099","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"condition","value":"AL Amyloidosis","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"modality","value":"CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"modality","value":"Corticosteroid","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"sample_size","value":"n=388","value_numeric":388},{"paper_doi":"10.1182/blood.2025032099","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"warning","value":"Age distribution and baseline organ staging (e.g., Mayo stage) are not described in the abstract, which limits applicability to specific patient subgroups.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"warning","value":"Median overall survival was not reached or not explicitly reported in the abstract, so absolute survival benefit in months cannot be quantified from this source alone.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032099","tag_type":"warning","value":"Subcutaneous daratumumab formulation is used here — results may not be directly interchangeable with IV daratumumab data from other studies.","value_numeric":null}],"summaries":{"what_studied":"Phase 3 ANDROMEDA trial comparing D-VCd (subcutaneous daratumumab + bortezomib/cyclophosphamide/dexamethasone, up to 24 cycles) vs. VCd alone (6 cycles) in 388 newly diagnosed AL amyloidosis patients; this is the preplanned final survival analysis with a median follow-up of 61.4 months.","key_result":"Hematologic CR rate was 59.5% with D-VCd vs. 19.2% with VCd (OR 6.03; P<0.0001). D-VCd significantly improved overall survival (HR 0.62; 95% CI 0.42–0.90; P=0.0121) and major organ deterioration-PFS (HR 0.44; 95% CI 0.31–0.63; P<0.0001). Cardiac and renal response rates were 2–3× higher with D-VCd.","limitations":"- Open-label design may introduce assessment bias.\n- Crossover or subsequent therapy details post-progression are not described, which could confound OS results.\n- Median OS was not reported, limiting quantification of absolute survival benefit.","practice_takeaway":"D-VCd now has mature data showing a statistically significant OS benefit over VCd in newly diagnosed AL amyloidosis — reinforcing it as the standard frontline regimen. Achieving hematologic or cardiac CR should remain a key treatment goal, as both are independently linked to better survival outcomes."}},{"doi":"10.1182/bloodadvances.2025019323","pmid":"42085642","title":"Infections in patients receiving daratumumab for newly diagnosed multiple myeloma: a pooled analysis of MAIA and ALCYONE","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-05-05T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2025019323","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-03T13:39:01.070Z","updated_at":"2026-07-03T13:39:01.070Z","tags":[{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"generic","value":"melphalan","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"generic","value":"prednisone","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"modality","value":"CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"sample_size","value":"n=1429","value_numeric":1429},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"study_design","value":"Pooled Analysis of Randomized Controlled Trials","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"warning","value":"Exposure-adjusted rates account for longer treatment duration in daratumumab arms, but the method of adjustment (first-event only per patient per EAIR calculation) may underestimate cumulative infection burden in long-term survivors.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"warning","value":"Study was industry-sponsored (Johnson & Johnson); several authors are employees or have financial ties to the sponsor.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"warning","value":"The two pooled trials (MAIA and ALCYONE) had different backbone regimens and treatment durations, which may limit direct comparability of infection rates between studies.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019323","tag_type":"warning","value":"This is a post hoc pooled analysis; no formal inferential statistics were performed, so comparisons between groups are descriptive only.","value_numeric":null}],"summaries":{"what_studied":"Pooled post hoc analysis of infection incidence, timing, and management in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients from the phase 3 MAIA (D-Rd vs Rd) and ALCYONE (D-VMP vs VMP) trials; pooled safety population of 1,429 patients with median age 72 years (range 40–93) and median follow-up of 64.5 months (MAIA) and 86.7 months (ALCYONE).","key_result":"Crude incidence of grade 3/4 infections was higher with daratumumab-based regimens vs controls (36.9% vs 22.4%), but exposure-adjusted incidence rates (EAIRs) were comparable (1.19 vs 1.41 per 100 patient-months). Grade 5 infection rates were low (3.0% vs 1.5%) with similar EAIRs (0.07 vs 0.08). Infections led to treatment discontinuation in ~2% of patients across all arms. The highest grade 3/4 infection risk occurred in the first 6 months of treatment in both groups.","limitations":"- Post hoc, descriptive analysis with no formal statistical comparisons.\n- Clinical trial populations may have better baseline performance status than real-world NDMM patients, potentially underestimating infection risk.\n- IMWG infection prophylaxis guidelines were published after full enrollment, so prophylaxis was not standardized per current recommendations.","practice_takeaway":"When counseling transplant-ineligible NDMM patients starting daratumumab-based therapy, emphasize that the first 6 months carry the highest infection risk and warrant close monitoring plus prophylaxis per current IMWG guidelines (levofloxacin antibacterial, acyclovir antiviral, and trimethoprim–sulfamethoxazole for high-risk patients). Exposure-adjusted infection rates are similar to non-daratumumab regimens, so the survival benefit of adding daratumumab is not offset by a meaningfully higher per-month infection burden."}},{"doi":"10.1182/blood.2025032145","pmid":"42066212","title":"How I Treat Plasma Cell Leukemia","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-05-01T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025032145","source_score":33,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-05-06","doi":"10.1182/blood.2025032145","days":"14","issn":"0006-4971","rank":"6","field":"Clinical Medicine","score":"33","category":"Hematology","categories":["Hematology"],"_categories":["Hematology"]},"pubmed":{"doi":"10.1182/blood.2025032145","title":"How I Treat Plasma Cell Leukemia.","journal":"Blood","methods":"","results":"","abstract":"$30","keywords":[],"pubmed_id":"42066212","conclusions":"","publication_date":"2026-05-01T00:00:00"},"crossref":{"DOI":"10.1182/blood.2025032145","URL":"https://doi.org/10.1182/blood.2025032145","ISSN":["0006-4971","1528-0020"],"link":[{"URL":"https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2025032145/2516783/blood.2025032145.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https://ashpublications.org/blood/article-pdf/doi/10.1182/blood.2025032145/2516783/blood.2025032145.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["How I Treat Plasma Cell Leukemia"],"author":[{"given":"Samer","family":"Al Hadidi","sequence":"first","affiliation":[{"name":"UT Southwestern Medical Center, Dallas, Texas, United States"}]},{"given":"Frits","family":"van Rhee","sequence":"additional","affiliation":[{"name":"University of Arkansas for Medical Sciences, Little Rock, Pennsylvania, United States"}]},{"given":"Larry D.","family":"Anderson","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas, Texas, United States"}]}],"issued":{"date-parts":[[2026,5,1]]},"member":"234","prefix":"10.1182","source":"Crossref","volume":null,"created":{"date-time":"2026-05-01T18:41:02Z","timestamp":1777660862000,"date-parts":[[2026,5,1]]},"indexed":{"date-time":"2026-05-04T18:15:19Z","timestamp":1777918519818,"date-parts":[[2026,5,4]]},"subject":[],"abstract":"$31","language":"en","relation":{},"resource":{"primary":{"URL":"https://ashpublications.org/blood/article/doi/10.1182/blood.2025032145/568165/How-I-Treat-Plasma-Cell-Leukemia"}},"subtitle":[],"deposited":{"date-time":"2026-05-01T18:41:02Z","timestamp":1777660862000,"date-parts":[[2026,5,1]]},"issn-type":[{"type":"print","value":"0006-4971"},{"type":"electronic","value":"1528-0020"}],"published":{"date-parts":[[2026,5,1]]},"publisher":"American Society of Hematology","reference":null,"short-title":[],"update-policy":"https://doi.org/10.1182/blood.2019cm0000","article-number":"blood.2025032145","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"original-title":[],"container-title":["Blood Journal"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,5,1]]},"references-count":0,"short-container-title":[],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1182/blood.2025032145","is_oa":false,"title":"How I Treat Plasma Cell Leukemia","updated":"2026-05-05T11:59:32+00:00","published_date":"2026-05-01","best_oa_location":null}},"created_at":"2026-05-07T22:51:14.232Z","updated_at":"2026-05-14T15:13:26.918Z","tags":[{"paper_doi":"10.1182/blood.2025032145","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"condition","value":"Plasma Cell Leukemia","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"Autologous Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"BCL-2 Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"Bispecific Antibody","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"CAR-T Cell Therapy","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"Immunomodulatory Drug","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"warning","value":"Level of evidence set to 5 (expert opinion/narrative review); no prospective trial data specific to PCL were reported.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"warning","value":"No sample size tag was applied — this is a narrative review with no single study population; individual cases are illustrative only.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"warning","value":"Publication date is listed as 2026-05-01, which is in the future relative to most available trial data; recency of cited evidence could not be verified from the abstract alone.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032145","tag_type":"warning","value":"Study design labeled 'Narrative Review' rather than 'Systematic Review' as no formal systematic search methodology is described in the abstract.","value_numeric":null}],"summaries":{"what_studied":"This review synthesizes current evidence on the diagnosis and treatment of plasma cell leukemia (PCL), defined as ≥5% circulating plasma cells in peripheral blood in patients meeting MM criteria, covering established and novel therapeutic approaches including BCMA-directed bispecific antibodies, CAR-T cell therapy, GPRC5D-targeted therapy, and BCL-2 inhibition.","key_result":"Novel agents targeting BCMA (bispecific antibodies, CAR-T) and GPRC5D, along with BCL-2 inhibition, show promise in both primary and secondary PCL; however, no robust prospective trial data specific to PCL exist, as these patients have largely been excluded from MM trials.","limitations":"- Treatment evidence is almost entirely extrapolated from MM trials that excluded PCL patients, with no dedicated prospective RCTs in PCL.\n- The rarity of PCL means most guidance comes from case series, retrospective data, and illustrative clinical cases presented in this review.\n- High-risk molecular features and extramedullary disease make outcomes difficult to generalize across patients.","practice_takeaway":"Consider BCMA-directed therapies (bispecific antibodies or CAR-T) and GPRC5D-targeted agents for PCL patients, particularly those with relapsed/refractory disease, while recognizing that evidence is largely extrapolated from MM studies. Enrollment in dedicated prospective PCL trials should be strongly prioritized whenever available."}},{"doi":"10.1182/bloodadvances.2025019036","pmid":"41925575","title":"BCMA/CD19 dual-targeting CAR T-cell therapy in older patients with newly diagnosed multiple myeloma: a phase 1 study","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-04-02T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2025019036","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-16T13:54:37.301Z","updated_at":"2026-06-16T13:54:37.301Z","tags":[{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"brand","value":"AZD0120","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"generic","value":"bortezomib","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"modality","value":"CAR T-Cell Therapy","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"modality","value":"Immunomodulatory Agent","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"modality","value":"Proteasome Inhibitor","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"sample_size","value":"n=8","value_numeric":8},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"study_design","value":"Phase 1 Single-Arm Trial","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"warning","value":"AZD0120 was formerly known as GC012F; clinicians searching the literature may need to use both names.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"warning","value":"Extremely small sample (n=8) — efficacy and safety estimates are highly uncertain and should be interpreted with caution.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"warning","value":"Median follow-up of 9.8 months is insufficient to assess progression-free or overall survival; MRD negativity at month 12 is based on only 2 evaluable patients.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2025019036","tag_type":"warning","value":"No formal dose-response analysis was possible given the small N across two dose levels.","value_numeric":null}],"summaries":{"what_studied":"Phase 1 single-arm study evaluating AZD0120 (formerly GC012F), a BCMA/CD19 dual-targeting autologous CAR T-cell therapy, as frontline treatment in 8 patients with newly diagnosed multiple myeloma (NDMM) aged ≥70 years, following 2 cycles of VRD induction, at doses of 1.5×10⁵ or 3×10⁵ cells/kg, with a median follow-up of 9.8 months post-infusion.","key_result":"All 8 patients (100%) achieved stringent complete response (sCR) and MRD negativity at 10⁻⁶ by Euroflow at 1 month; MRD negativity was maintained in 100% of evaluable patients at month 6 (n=7) and month 12 (n=2). Grade ≥3 toxicities included neutropenia (75%), leukopenia (50%), and lymphopenia (25%); CRS occurred in 4 patients (50%), all grade 1; no ICANS was observed.","limitations":"Very small sample size (n=8) limits generalizability; short median follow-up (9.8 months) precludes durability conclusions; single-arm design with no comparator group.","practice_takeaway":"AZD0120 CAR T-cell therapy after VRD induction produced universal sCR and MRD negativity in older and frail NDMM patients with a manageable toxicity profile, suggesting this approach may be feasible even in patients ≥70 years. Larger studies with longer follow-up are needed before routine clinical adoption."}}],"initialOffset":22,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Proteasome Inhibitor"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Proteasome Inhibitor"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Proteasome Inhibitor"}}}]]

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