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:Tbf9,Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), affecting up to one-third of pediatric SLE patients. Timely induction therapy is critical in proliferative LN to prevent progression to kidney failure or death. Intravenous cyclophosphamide (IVCP) has long been a standard induction agent, but its toxicity profile has prompted interest in mycophenolate mofetil (MMF) as a potentially safer alternative. However, data comparing the efficacy and safety of MMF versus IVCP in children are limited and inconclusive. To systematically review and synthesise existing evidence comparing the efficacy and safety of MMF versus IVCP for induction therapy in pediatric patients with proliferative LN. A comprehensive search was conducted in six electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, CINAHL, and CENTRAL) on June 2, 2025. Reference lists of included articles were also manually screened. We included randomised controlled trials and observational studies published in English that directly compared MMF and IVCP as induction therapies in pediatric patients with biopsy-proven proliferative LN. Studies were required to report at least one of the following outcomes: kidney remission (complete or partial), adverse events, kidney failure, or death. Eligible participants were children aged ≤ 17 years with a diagnosis of proliferative LN based on the American College of Rheumatology (ACR) criteria. Interventions involved MMF plus corticosteroids versus IVCP plus corticosteroids, with comparable adjunctive therapies. Authors independently screened articles, extracted data, and assessed study quality using the RoB2 tool for RCTs and the ROBINS-I tool for observational studies. A random-effects meta-analysis was conducted to estimate pooled risk ratios (RRs) for complete remission. Sensitivity analyses and funnel plots were used to assess robustness and publication bias. Out of 1,633 screened records, seven studies met the inclusion criteria, six observational studies (n = 282) and one RCT (n = 24). Meta-analysis of the observational studies revealed no significant difference in complete remission between the MMF and IVCP groups (pooled RR: 1.01; 95% CI: 0.78-1.29; I The analysis was limited by the predominance of observational studies and only one small pediatric RCT with a high risk of bias. Variability in outcome definitions, inconsistent reporting of baseline disease severity, and lack of subgroup analysis limited further interpretation. Small study numbers precluded a formal assessment of publication bias. The efficacy of MMF appears to be similar to IVCP for induction therapy in pediatric proliferative LN, with a potentially more favourable safety profile. These findings support MMF as a viable alternative to IVCP; however, robust, multicenter pediatric RCTs are urgently needed to establish definitive treatment recommendations and guide clinical practice. PROSPERO: CRD42024533313 available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024533313.31:T695,Systemic sclerosis (SSc) is an autoimmune disease characterized by autoantibody production, fibrosis, and vasculopathy. The coexistence of ANCA-associated vasculitides (AAV) in SSc is rare and poorly characterized, with limited data on the impact of treatments, particularly high-dose glucocorticoids (GCs), on both conditions. This study aimed to describe the clinical phenotype, management, and outcomes of patients with overlapping SSc and AAV. We conducted a multicenter retrospective study in 18 French centers, including patients who met the 2013 ACR/EULAR criteria for SSc and the 2022 ACR/EULAR criteria for AAV. Clinical, biologic, and radiologic data were collected. We included 30 patients (median age 51.5 years, 83% female). SSc preceded AAV in all cases; 27% had diffuse cutaneous SSc, while 73% had limited cutaneous SSc. Anti-Scl70 antibodies were detected in 50%, and interstitial lung disease (ILD) was present in 80%, predominantly with a fibrosing non-specific interstitial pneumonia pattern (54%). AAV was microscopic polyangiitis in 90%, with MPO-ANCA positivity in 93%. Renal involvement was common (76%), with a median serum creatinine of 170 μmol/l (IQR 120-361) and proteinuria of 2 g/g (IQR 0.9-2.3). All patients received GCs in combination with cyclophosphamide (50%) or rituximab (47%). No cases of scleroderma renal crisis were observed. SSc manifestations, including ILD and skin involvement, remained stable during follow-up. AAV, predominantly microscopic polyangiitis with MPO-ANCA, can occur in SSc, particularly in patients with fibrosing ILD and anti-Scl70. Standard vasculitis treatments appear to be effective and do not worsen outcomes in SSc.32:T8f3, Introduction Systemic sclerosis (SSc) is an autoimmune disease characterized by autoantibody production, fibrosis, and vasculopathy. The coexistence of ANCA‐associated vasculitides (AAV) in SSc is rare and poorly characterized, with limited data on the impact of treatments, particularly high‐dose glucocorticoids (GCs), on both conditions. This study aimed to describe the clinical phenotype, management, and outcomes of patients with overlapping SSc and AAV. Methods We conducted a multicenter retrospective study in 18 French centers, including patients who met the 2013 ACR/EULAR criteria for SSc and the 2022 ACR/EULAR criteria for AAV. Clinical, biologic, and radiologic data were collected. Results We included 30 patients (median age 51.5 years, 83% female). SSc preceded AAV in all cases; 27% had diffuse cutaneous SSc, while 73% had limited cutaneous SSc. Anti‐Scl70 antibodies were detected in 50%, and interstitial lung disease (ILD) was present in 80%, predominantly with a fibrosing non‐specific interstitial pneumonia pattern (54%). AAV was microscopic polyangiitis in 90%, with MPO‐ANCA positivity in 93%. Renal involvement was common (76%), with a median serum creatinine of 170 μmol/l (IQR 120‐361) and proteinuria of 2 g/g (IQR 0.9‐2.3). All patients received GCs in combination with cyclophosphamide (50%) or rituximab (47%). No cases of scleroderma renal crisis were observed. SSc manifestations, including ILD and skin involvement, remained stable during follow‐up. Conclusion AAV, predominantly microscopic polyangiitis with MPO‐ANCA, can occur in SSc, particularly in patients with fibrosing ILD and anti‐Scl70. Standard vasculitis treatments appear to be effective and do not worsen outcomes in SSc. 33:Tb20,Abstract Patients with multiple myeloma bearing a deletion of chromosome 17p (del(17p)), mutation of TP53 , or both have poorer prognosis compared to patients without these aberrations. We investigated the activity and mechanism of melflufen (melphalan flufenamide) in myeloma models with wild type TP53 ( TP53 wt) and complete TP53 deletion ( TP53 −/− ) and assessed the efficacy of melflufen in patients with del(17p) and/or TP53 mutation. Ex vivo data from myeloma plasma cells (PC) showed comparable activity of melflufen in del(17p), TP53 −/− , and TP53 wt samples. scRNAseq data demonstrated that melflufen sensitive PCs had lower expression of p53 target genes and higher expression of genes associated with DNA damage repair and cell cycle checkpoints. Irrespective of TP53 status, melflufen induced apoptosis, DNA damage, and mitochondrial dysfunction, while only in TP53 −/− cells, it led to changes in expression of cell cycle checkpoint and apoptosis genes. Post-hoc analysis of the OCEAN trial melflufen-treated del(17p) patient population also demonstrated favorable progression free survival compared to pomalidomide-treated cohort. Our insights into the molecular mechanisms of melflufen activity in TP53 −/− myeloma support its clinical efficacy and application in the del(17p) and TP53 −/− patient population. Trial registration NCT03151811, registration 2017-05-09. 34:T561,K.A., Y.D., K.W.M., J.O., S.S.G. are employees of and receives stock or stock options from Oncopeptides. S.N. is an employee of, has participated on a data safety monitoring board or advisory board for, and receives stock or stock options from Oncopeptides. M.T. is a consultant of and receives stock or stock options from Oncopeptides. A.S., F.L., are former employees of and receive stock or stock options from Oncopeptides. F.S. has received grants or contracts from Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Targovax, and Sanofi; payment or honoraria for lectures or speakers’ bureau participation from AbbVie, Amgen, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Oncopeptides, Pfizer, Sanofi, SkyliteDX, and Takeda; serving on a data safety monitoring or advisory board for AbbVie, Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, and Takeda; and stock or stock options from Nordic Nanovector. P.So. has received grants or contracts from Amgen, Celgene, Janssen, Takeda, and SkylineDx. C.A.H. has received research funding from Oncopeptides related to this work, and from IMI2 projects HARMONY and HARMONY PLUS, WntResearch, Orion, Kronos Bio, Novartis, Celgene, Zentalis Pharmaceuticals for unrelated work, plus honoraria or personal fees from Amgen and Autolus. The remaining authors declare no competing financial interests.25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Alkylating Agent: modality Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Alkylating Agent (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":"10.1002/art.70303","pmid":"42663235","title":"Cancer in systemic sclerosis: clinical associations and prognostic impact from the\n EUSTAR\n registry","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2026-08-28T00:00:00.000Z","url":"https://doi.org/10.1002/art.70303","source_score":5,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-05T06:20:02.207Z","updated_at":"2026-09-05T06:20:02.207Z","tags":[{"paper_doi":"10.1002/art.70303","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"condition","value":"Cancer","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"condition","value":"Interstitial Lung Disease","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"condition","value":"Systemic Sclerosis","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"sample_size","value":"n=908","value_numeric":908},{"paper_doi":"10.1002/art.70303","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"study_design","value":"Nested Case-Control Study","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"warning","value":"Cyclophosphamide association with cancer is observational and may reflect confounding by indication (sicker patients receiving treatment), not causation.","value_numeric":null},{"paper_doi":"10.1002/art.70303","tag_type":"warning","value":"The total sample size of 908 represents 454 matched pairs (cases + controls); the n=908 tag reflects the full analytic cohort. The impact_flag 'practice_changing' is applied because the study directly informs stratified surveillance recommendations, though prospective validation is still needed.","value_numeric":null}],"summaries":{"what_studied":"A nested case-control study within the EUSTAR registry compared 454 SSc patients who developed cancer (classified as synchronous, subsequent, or previous relative to SSc onset) with 454 cancer-free SSc controls matched for age and disease duration, analyzing clinical, serological, and treatment associations as well as survival outcomes.","key_result":"Synchronous cancers were linked to anti-POLR3 (OR 2.06), U1RNP (OR 3.56), and smoking (OR 1.57); lung cancer (mainly subsequent) was associated with ILD (OR 2.00), anti-topoisomerase (OR 2.61), and smoking; subsequent cancers were the strongest driver of excess mortality; radiation therapy did not increase mortality or new-onset ILD.","limitations":"Retrospective registry design limits causal inference; cancer diagnoses and treatments relied on registry reporting, which may be incomplete; controls were matched only on age and disease duration, leaving residual confounding possible.","practice_takeaway":"Stratify cancer surveillance in SSc by antibody profile and disease timing — patients with anti-POLR3, anti-topoisomerase, ILD, or smoking history warrant closer monitoring, especially for breast and lung cancers. Subsequent (post-diagnosis) cancers carry the worst survival impact, so ongoing surveillance beyond early disease is essential."}},{"doi":"10.1182/bloodadvances.2026020293","pmid":"42537695","title":"Phase I/II Trial of Evomela for Autologous Transplant in Myeloma: Schedule Optimization and Matched Comparison with MEL200","journal_title":"Blood Advances","journal_issn":"2473-9529","published_at":"2026-07-31T00:00:00.000Z","url":"https://doi.org/10.1182/bloodadvances.2026020293","source_score":9,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-06T13:22:15.525Z","updated_at":"2026-08-06T13:22:15.525Z","tags":[{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"brand","value":"Evomela","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"generic","value":"melphalan","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"sample_size","value":"n=60","value_numeric":60},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"study_design","value":"Phase I/II Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"warning","value":"Infusion schedule (short vs. long) did not significantly affect outcomes, but the trial may have been underpowered to detect small differences.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"warning","value":"The paper is published July 31, 2026; today's date is August 6, 2026 — this is a very recent publication and may not yet be reflected in clinical guidelines.","value_numeric":null},{"paper_doi":"10.1182/bloodadvances.2026020293","tag_type":"warning","value":"The 'practice_changing' impact flag is tentative — the propensity-matched PFS benefit (PBE=0.90) is suggestive but not definitive; results should be interpreted cautiously until confirmed in larger randomized trials.","value_numeric":null}],"summaries":{"what_studied":"This prospective Phase I/II trial (NCT03417284) tested Evomela (propylene-glycol-free melphalan) at 200 or 225 mg/m² with short (30–60 min) vs. long (8–9 hr) infusion schedules as conditioning before ASCT in 60 newly diagnosed multiple myeloma patients, using a Bayesian design to optimize dose/schedule and characterize pharmacokinetics.","key_result":"No grade ≥4 non-hematologic toxicities or day-100 non-relapse mortality occurred. MRD-negative sCR/CR at day 90 was 45% overall (43% short infusion vs. 47% long infusion — similar between arms). Higher melphalan AUC was strongly linked to MRD-negative sCR/CR (posterior probability of benefit [PBE] = 0.99) without added toxicity. In propensity-matched comparison, Evomela showed longer PFS vs. standard MEL200 (PBE = 0.90).","limitations":"- Small sample size (n=60) limits definitive conclusions on PFS and subgroup effects.\n- Propensity-matched comparison with MEL200 is observational and subject to unmeasured confounding.\n- Higher AUC was associated with MRD-negative CR but not independently with PFS, leaving the clinical translation of AUC-guided dosing uncertain.","practice_takeaway":"Evomela appears safe for dose intensification up to 225 mg/m² in ASCT conditioning for myeloma, with no excess severe non-hematologic toxicity. Clinicians may consider AUC-guided Evomela dosing as a platform to improve MRD-negative response rates, pending larger confirmatory trials."}},{"doi":"10.1200/jco-25-02463","pmid":"42418736","title":"Intracranial Injection of Investigational Ex Vivo Expanded and Activated Gamma-Delta T Cells Engineered With a Methylguanine-DNA Methyltransferase–Expressing Lentivector in Patients With Primary Glioblastoma","journal_title":"Journal of Clinical Oncology","journal_issn":"0732-183X","published_at":"2026-07-08T00:00:00.000Z","url":"https://doi.org/10.1200/jco-25-02463","source_score":26,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-14T13:24:22.319Z","updated_at":"2026-07-14T13:24:22.319Z","tags":[{"paper_doi":"10.1200/jco-25-02463","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"brand","value":"Temodar","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"condition","value":"Glioblastoma","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"generic","value":"temozolomide","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"modality","value":"Gamma-Delta T Cell Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"modality","value":"Gene-Modified Cell Therapy","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"sample_size","value":"n=13","value_numeric":13},{"paper_doi":"10.1200/jco-25-02463","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"study_design","value":"Phase I Clinical Trial","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"warning","value":"Brand tag 'Temodar' added for temozolomide; confirm preferred institutional name if needed.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"warning","value":"Median OS (15.6 months) equals median follow-up (15.6 months), suggesting survival data are immature and likely not yet fully evaluable.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"warning","value":"No comparator arm; PFS and OS benchmarking against standard-of-care (e.g., Stupp protocol) is not directly performed in this report.","value_numeric":null},{"paper_doi":"10.1200/jco-25-02463","tag_type":"warning","value":"Only 13 of 23 enrolled patients were treated; reasons for non-treatment are not detailed, which may introduce selection bias.","value_numeric":null}],"summaries":{"what_studied":"A phase I trial evaluating intracranial injection of MGMT-expressing lentivector-engineered gamma-delta (γδ) T cells (DRI) combined with IV/oral TMZ in 13 treated patients with newly diagnosed GBM (92% IDH-WT, 54% MGMT unmethylated), across 3 dose cohorts (1, 3, or up to 6 doses of 1×10⁷ cells) delivered via Rickham catheter.","key_result":"No dose-limiting toxicities, CRS, or neurotoxicity were observed. Median PFS was 8.0 months (single dose, Cohort 1), 9.9 months (all patients), and 16.1 months (repeated doses, Cohorts 2–3); median OS was 15.6 months across all treated patients at median follow-up of 15.6 months.","limitations":"Very small treated sample (n=13); no control arm for direct comparison; short and variable follow-up limits survival conclusions.","practice_takeaway":"This early-phase signal suggests intracranial γδ T cell therapy combined with TMZ is feasible and well-tolerated in GBM, with repeated dosing appearing to improve PFS. Larger controlled trials are needed before clinical adoption."}},{"doi":"10.1158/2159-8290.cd-25-0231","pmid":"42001506","title":"Therapy-Related Mutational Signatures in Subsequent Neoplasms among Survivors of Childhood Cancer","journal_title":"Cancer Discovery","journal_issn":"2159-8274","published_at":"2026-06-24T00:00:00.000Z","url":"https://doi.org/10.1158/2159-8290.cd-25-0231","source_score":29,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-27T13:27:52.480Z","updated_at":"2026-06-27T13:27:52.480Z","tags":[{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"category","value":"Oncology","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"condition","value":"Breast Cancer","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"condition","value":"Childhood Cancer","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"condition","value":"Meningioma","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"condition","value":"Subsequent Neoplasm","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"condition","value":"Thyroid Cancer","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"generic","value":"nitrogen mustard","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"modality","value":"Platinum Chemotherapy","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"modality","value":"Radiation Therapy","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"sample_size","value":"n=200","value_numeric":200},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"study_design","value":"Genomic Sequencing Study (Retrospective Cohort)","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"warning","value":"Sample size of n=200 refers to subsequent neoplasm specimens, not unique patients (160 survivors); some analyses (e.g., multi-sample) are based on a subset of 19 survivors.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"warning","value":"Study design is labeled as a retrospective genomic cohort; the authors did not use a strict randomized or prospective design, so causal attribution of mutational signatures to specific treatments is associative, not confirmatory.","value_numeric":null},{"paper_doi":"10.1158/2159-8290.cd-25-0231","tag_type":"warning","value":"The 'practice_changing' impact flag is applied because therapy-linked genomic signatures in SNs could directly inform treatment selection, but prospective clinical validation is not yet available.","value_numeric":null}],"summaries":{"what_studied":"Whole-genome, exome, and RNA sequencing of 200 subsequent neoplasms (breast, meningioma, thyroid) from 160 childhood cancer survivors, with a median of 26.4 years between primary treatment and subsequent tumor development, to identify therapy-related mutational signatures.","key_result":"Radiation correlated with increased indel signature ID5 and NF2-disrupting/kinase fusion rearrangements; nitrogen mustard treatment correlated with elevated 'flat' SBS5 signature in breast and meningioma; platinum therapy correlated with NF2 splice-site variants in meningioma. Meningioma and thyroid SNs showed enrichment for driver gene rearrangements vs. de novo tumors. Multi-sample analysis of 19 survivors revealed clonally independent meningiomas.","limitations":"Cross-sectional sequencing of SNs without matched primary tumor genomes limits causal inference; study includes only three SN types (breast, meningioma, thyroid), which may not generalize to other subsequent neoplasms; in vitro nitrogen mustard findings may not fully replicate in vivo mutational dynamics.","practice_takeaway":"Clinicians managing childhood cancer survivors should be aware that radiation and alkylating agents leave lasting genomic 'fingerprints' in subsequent tumors decades later, which may help guide targeted treatment of those SNs. Surveillance strategies and treatment selection for subsequent neoplasms in survivors could be informed by prior therapy type."}},{"doi":"10.1038/s41408-026-01537-4","pmid":"42337234","title":"Characteristics and outcomes of secondary hematological malignancies following autologous stem cell transplantation for multiple myeloma","journal_title":"Blood Cancer Journal","journal_issn":"2044-5385","published_at":"2026-06-23T00:00:00.000Z","url":"https://doi.org/10.1038/s41408-026-01537-4","source_score":8,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:08.422Z","updated_at":"2026-06-28T13:27:08.422Z","tags":[{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"condition","value":"Second Primary Malignancy","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"condition","value":"Therapy-Related B-Cell Acute Lymphoblastic Leukemia","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"condition","value":"Therapy-Related Myeloid Neoplasm","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"generic","value":"lenalidomide","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"modality","value":"Autologous Stem Cell Transplantation","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"modality","value":"Immunomodulatory Agent","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"sample_size","value":"n=3401","value_numeric":3401},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"warning","value":"Brand names for lenalidomide (Revlimid) and cyclophosphamide (Cytoxan) were not mentioned in the abstract; only generic names are tagged.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"warning","value":"The 32-year study span (1990–2022) encompasses major shifts in MM treatment; era-related confounding may affect risk factor estimates. Readers should interpret multivariate predictors with caution.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01537-4","tag_type":"warning","value":"The paper's DOI year (2026) is consistent with today's date, but the journal volume/issue details were not provided for independent verification.","value_numeric":null}],"summaries":{"what_studied":"This retrospective study examined the incidence, characteristics, and outcomes of second hematological malignancies (SHM) in 3,401 multiple myeloma (MM) patients who underwent autologous stem cell transplantation (auto-SCT) at a single institution between 1990 and 2022.","key_result":"110 patients (3.2%) developed SHM — 98 therapy-related myeloid neoplasms (t-MN), 11 therapy-related B-ALL, and 1 mixed phenotype acute leukemia. Cumulative SHM incidence rose significantly from the pre-novel agent era to the novel agent era (1.1% vs. 2.0% at 60 months; P=0.03). Independent predictors included alkylator-based induction, radiation therapy, complete response after auto-SCT, cyclophosphamide mobilization, and lenalidomide maintenance. TP53 mutations were found in 40% of t-MN cases. SHM was associated with inferior overall survival.","limitations":"Single-institution retrospective design limits generalizability. Evolving treatment protocols over a 32-year span introduce significant era-related confounding. Causal inference is constrained by the observational nature of the data.","practice_takeaway":"Clinicians should counsel MM patients — especially those receiving lenalidomide maintenance, alkylator-based induction, or cyclophosphamide mobilization — about the rising risk of SHM after auto-SCT. As MM survival improves, routine long-term monitoring for secondary hematological malignancies should be part of survivorship care."}},{"doi":"10.1111/pcmr.70104","pmid":"42322017","title":"Pegargiminase Suppresses the Fanconi Anemia Pathway and Promotes Melphalan‐Induced\n DNA\n Double‐Strand Breaks in Uveal Melanoma","journal_title":"Pigment Cell & Melanoma Research","journal_issn":"1755-1471","published_at":"2026-06-19T00:00:00.000Z","url":"https://doi.org/10.1111/pcmr.70104","source_score":2,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-28T13:27:21.300Z","updated_at":"2026-06-28T13:27:21.300Z","tags":[{"paper_doi":"10.1111/pcmr.70104","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"brand","value":"ADI-PEG20","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"category","value":"Dermatology","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"condition","value":"Uveal Melanoma","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"generic","value":"melphalan","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"generic","value":"pegargiminase","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"modality","value":"Arginine-Depleting Enzyme","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"study_design","value":"Preclinical In Vitro Study","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"warning","value":"Age/sex tags are inferred from cell line origins and are not explicitly reported in the paper.","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"warning","value":"Industry funding (Polaris Pharmaceuticals, manufacturer of pegargiminase) and author conflict of interest should be noted when interpreting results.","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"warning","value":"The impact_flag 'practice_changing' reflects the mechanistic novelty and planned clinical translation, not established clinical benefit.","value_numeric":null},{"paper_doi":"10.1111/pcmr.70104","tag_type":"warning","value":"This is a preclinical cell-line-only study; no animal or human data are included, so clinical conclusions are speculative pending the planned ATOMIC-UM trial.","value_numeric":null}],"summaries":{"what_studied":"This preclinical study tested whether combining pegargiminase (ADI-PEG20), an arginine-depleting enzyme, with melphalan (an FDA-approved alkylating agent for hepatic uveal melanoma metastases) enhanced cytotoxicity in ASS1-deficient uveal melanoma cell lines (92.1, MP41, Mel270) using 2D culture proliferation, cytotoxicity, cell cycle, DNA double-strand break (DSB), and RNA-seq assays over 48–96 hours.","key_result":"The combination of ADI-PEG20 and melphalan produced at least additive antiproliferative effects in ASS1-deficient lines and a **fivefold synergistic increase in DNA double-strand breaks** versus control in 92.1 cells; ADI-PEG20 downregulated multiple Fanconi anemia (FA) pathway genes (FANCD2, FANCI, FANCA, FANCB, FANCE, BRIP1, EME1, UBE2T), and the combination triggered caspase- and PARP-dependent apoptosis in 92.1 cells. ASS1 overexpression abolished FA pathway suppression, confirming ASS1 dependence of the effect.","limitations":"- All experiments were conducted in 2D cell line models only; no in vivo validation was performed.\n- Significant combination synergy (apoptosis, DSBs) was observed in only one of two primary ASS1-deficient lines tested (92.1 but not MP41), limiting generalizability.\n- The study was funded by Polaris Pharmaceuticals, the manufacturer of ADI-PEG20, with one author being a Polaris employee.","practice_takeaway":"Pegargiminase suppresses Fanconi anemia DNA-repair genes and sensitizes ASS1-deficient uveal melanoma cells to melphalan-induced DNA damage — a combination now being advanced to a clinical trial (ATOMIC-UM). Clinicians treating hepatic-dominant uveal melanoma with chemosaturation melphalan should watch for results from this planned trial."}},{"doi":"10.1002/ajh.70371","pmid":"42252535","title":"Determinants of Long‐Term Benefit From High Dose Melphalan With Autologous Stem Cell Transplant in\n AL\n Amyloidosis","journal_title":"American Journal of Hematology","journal_issn":"0361-8609","published_at":"2026-06-07T00:00:00.000Z","url":"https://doi.org/10.1002/ajh.70371","source_score":11,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-12T13:24:26.263Z","updated_at":"2026-06-12T13:24:26.263Z","tags":[{"paper_doi":"10.1002/ajh.70371","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"condition","value":"AL Amyloidosis","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"generic","value":"melphalan","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"modality","value":"Autologous Stem Cell Transplant","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"sample_size","value":"n=475","value_numeric":475},{"paper_doi":"10.1002/ajh.70371","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"warning","value":"Specific patient demographics (age, sex distribution) were not reported in the abstract; sex tag 'mixed' is inferred from multi-center cohort convention.","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"warning","value":"The 12-month landmark design effectively excludes early deaths and non-completers; outcomes for the overall transplant-eligible population (including early progressors/deaths) may differ.","value_numeric":null},{"paper_doi":"10.1002/ajh.70371","tag_type":"warning","value":"The 'practice_changing' impact flag reflects the study's clear recommendation to restrict HDM/ASCT to select subgroups, but this is based on retrospective data and the finding should ideally be confirmed in a prospective trial.","value_numeric":null}],"summaries":{"what_studied":"Retrospective analysis of 475 transplant-eligible AL amyloidosis patients treated with standard intensity therapy ± high-dose melphalan (HDM) with autologous stem cell transplant (ASCT) at 6 centers (Europe/US, 2010–2024), evaluated at a 12-month landmark for time to progression (TTP) and survival by baseline risk factors, hematologic response, and HDM receipt.","key_result":"HDM was associated with longer TTP (HR 0.61) and benefited patients without CR after standard intensity therapy (median TTP 21.0 vs. 5.7 months without HDM); patients already in CR did not benefit. Gain/amp 1q independently shortened TTP (HR 2.18) regardless of HDM. Higher BMPC (>20%) worsened outcomes (HR 1.7), but this risk was attenuated with HDM. Daratumumab use was also associated with longer TTP (HR 0.44).","limitations":"Retrospective design with inherent selection bias in who received HDM. Six-center convenience cohort may limit generalizability. Competing-risk landmark design mitigates but does not eliminate confounding by early events.","practice_takeaway":"Consider HDM/ASCT selectively for AL amyloidosis patients who have not achieved CR after standard induction, or who have high bone marrow plasma cell burden (>20%) at diagnosis. Patients already in CR after standard therapy appear unlikely to gain further benefit from transplant."}},{"doi":"10.1186/s12882-026-05092-9","pmid":"42216130","title":"Clinicopathological characteristics and renal outcomes of IgA nephropathy in systemic lupus erythematosus: a case report and systematic literature review","journal_title":"BMC Nephrology","journal_issn":"1471-2369","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1186/s12882-026-05092-9","source_score":1,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-08T13:46:51.959Z","updated_at":"2026-06-08T13:46:51.959Z","tags":[{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"condition","value":"IgA Nephropathy","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"condition","value":"Lupus Nephritis","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"condition","value":"Systemic Lupus Erythematosus","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"modality","value":"Glucocorticoid","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"sample_size","value":"n=31","value_numeric":31},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"study_design","value":"Systematic Review with Pooled Case Series","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"warning","value":"Follow-up duration (median 16.5 months) is short; renal endpoint rates may underestimate true long-term risk.","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"warning","value":"Majority of patients were Asian (67.7%), which may limit applicability to other ethnic populations.","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"warning","value":"Study design is a pooled case series derived from a systematic review — not a traditional cohort study — limiting causal inference and generalizability.","value_numeric":null},{"paper_doi":"10.1186/s12882-026-05092-9","tag_type":"warning","value":"The 'level of evidence' is assigned as 4 given the retrospective case series nature; no controlled comparison group was available.","value_numeric":null}],"summaries":{"what_studied":"This systematic review pooled individual patient data from biopsy-proven IgA nephropathy (IgAN) cases in SLE patients (identified via PubMed/Embase through May 2025) to characterize their demographic, clinical, pathological, and renal outcomes over a median follow-up of 16.5 months.","key_result":"Among 31 patients (mean age 40.8 years; 67.7% Asian), immunosuppression achieved complete remission in 54.8%; however, 27.8% reached the renal endpoint (≥40% eGFR decline or ESRD), including 3 of 4 patients with AKI at presentation. Median proteinuria was 1.10 g/24 h; microscopic haematuria was present in 93.5%.","limitations":"- Methodology is entirely retrospective, based on pooled case reports — high risk of reporting and selection bias.\n- Small cohort (n=31) limits statistical power for subgroup comparisons.\n- Median follow-up of only 16.5 months is too short to capture long-term renal trajectories.","practice_takeaway":"In SLE patients with dominant mesangial IgA deposits, AKI at biopsy signals high renal risk — 3 of 4 such patients progressed to a renal endpoint. Early recognition of IgAN in SLE and prompt immunosuppression may improve outcomes, but long-term renal surveillance is warranted."}},{"doi":"10.1093/rheumatology/keag275","pmid":"42185210","title":"Incorporating frailty and disease severity into treatment decisions for older patients with ANCA-associated vasculitis","journal_title":"Rheumatology","journal_issn":"1462-0324","published_at":"2026-05-25T00:00:00.000Z","url":"https://doi.org/10.1093/rheumatology/keag275","source_score":4,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-30T13:22:47.028Z","updated_at":"2026-05-30T13:22:47.028Z","tags":[{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"condition","value":"ANCA-Associated Vasculitis","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"modality","value":"Anti-CD20 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"sample_size","value":"n=84","value_numeric":84},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"warning","value":"Frailty assessment methodology is not formally described; no validated frailty scale (e.g., Clinical Frailty Scale) is mentioned, which limits reproducibility of the treatment-selection approach.","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"warning","value":"The 'practice_changing' impact flag is applied cautiously — the retrospective design and small subgroup sizes mean results are hypothesis-generating rather than definitive.","value_numeric":null},{"paper_doi":"10.1093/rheumatology/keag275","tag_type":"warning","value":"Treatment group sizes are small (n=10 to 33 per group), making subgroup mortality and infection comparisons exploratory only.","value_numeric":null}],"summaries":{"what_studied":"Retrospective cohort study of 84 hospitalised patients aged ≥75 years with severe ANCA-associated vasculitis (AAV) who received remission induction with cyclophosphamide- or rituximab-based regimens between 2014 and 2021, with median follow-up of 21 months.","key_result":"One-year mortality was 20% overall; increasing age was independently associated with higher mortality (HR 4.15, 95% CI 1.62–10.6). Serious infection requiring readmission occurred in 27% within the first year. Low-dose rituximab was preferentially used in the oldest and most frail patients, while age was not significantly associated with serious infection risk (HR 1.18, 95% CI 0.47–2.93).","limitations":"- Retrospective, single-centre design with inherent selection bias toward hospitalised, severe-disease patients.\n- Small sample (n=84) limits statistical power across four treatment subgroups.\n- No validated frailty scoring tool is reported; frailty assessment appears clinical/subjective.","practice_takeaway":"For older patients (≥75) with severe AAV, consider tailoring induction therapy to frailty and disease severity — low-dose rituximab may be a reasonable choice for the oldest and most frail. A 20% one-year mortality in this high-risk group is broadly comparable to younger/less severe cohorts, suggesting that individualized de-escalation of immunosuppression does not appear to markedly worsen outcomes."}},{"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":"10.1016/j.urolonc.2026.04.010","pmid":"42120273","title":"Contemporary management of adrenocortical carcinoma: A narrative review","journal_title":"Urologic Oncology: Seminars and Original Investigations","journal_issn":"1078-1439","published_at":"2026-05-12T00:00:00.000Z","url":"https://doi.org/10.1016/j.urolonc.2026.04.010","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-22T13:22:21.639Z","updated_at":"2026-05-22T13:22:21.639Z","tags":[{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"condition","value":"Adrenocortical Carcinoma","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"generic","value":"cisplatin","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"generic","value":"doxorubicin","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"generic","value":"etoposide","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"generic","value":"mitotane","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"modality","value":"Adrenalectomy","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"modality","value":"Adrenocortical Suppressant","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"modality","value":"Cytotoxic Chemotherapy","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"modality","value":"Radiation Therapy","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"warning","value":"No sample size is reported; this is a narrative review, not a primary study.","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"warning","value":"Publication date (May 2026) is very recent; some referenced guideline data may not yet be widely accessible for verification.","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"warning","value":"Sex distribution of the studied population is not reported.","value_numeric":null},{"paper_doi":"10.1016/j.urolonc.2026.04.010","tag_type":"warning","value":"The study design is narrative rather than systematic, so selection bias in included literature cannot be excluded.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluates current strategies for diagnosing, staging, and treating adrenocortical carcinoma (ACC), including surgery, adjuvant mitotane, radiation, systemic chemotherapy, and emerging molecular/immunotherapeutic approaches, drawing from PubMed, Scopus, and international guidelines.","key_result":"Complete surgical resection (adrenalectomy with lymph node dissection) remains the only curative option; adjuvant mitotane plus radiation is standard post-surgery for high-risk features (incomplete resection, high grade, Ki67 >10%); EDP (etoposide-doxorubicin-cisplatin) plus mitotane is the standard of care for advanced disease.","limitations":"Narrative review design limits systematic appraisal of evidence; ACC rarity restricts large-scale RCTs, leaving many recommendations based on limited data; role of adjuvant chemotherapy remains undefined pending ongoing studies.","practice_takeaway":"For ACC with high-risk features (incomplete resection, high grade, Ki67 >10%), add adjuvant mitotane and radiation therapy post-surgery. For advanced disease, use the EDP–mitotane regimen and consider enrolling eligible patients in trials investigating targeted or immunotherapy approaches."}},{"doi":"10.1016/j.clml.2026.04.022","pmid":"42215355","title":"BRIDGE (OP-107): A Phase 2 Pharmacokinetic Study of Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Impaired Renal Function","journal_title":"Clinical Lymphoma Myeloma and Leukemia","journal_issn":"2152-2650","published_at":"2026-05-01T00:00:00.000Z","url":"https://doi.org/10.1016/j.clml.2026.04.022","source_score":23,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-06T13:36:15.032Z","updated_at":"2026-07-06T13:36:15.032Z","tags":[{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"condition","value":"Relapsed/Refractory Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"condition","value":"Renal Impairment","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"generic","value":"dexamethasone","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"generic","value":"melflufen","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"generic","value":"melphalan flufenamide","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"sample_size","value":"n=35","value_numeric":35},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"study_design","value":"Phase 2 Open-Label Study","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"warning","value":"Cohort 2a (severe renal impairment) had only 4 patients — PK and safety conclusions for this subgroup are very preliminary.","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"warning","value":"No brand name (proprietary) for melflufen was tagged as it was withdrawn from the market; clinicians should verify current regulatory status before considering use.","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"warning","value":"The impact_flag 'safety_signal' is applied due to 6 treatment-emergent adverse event deaths in 35 patients (17%), though the paper states no new safety signals were identified; clinicians should interpret this in the context of a heavily pre-treated RRMM population.","value_numeric":null},{"paper_doi":"10.1016/j.clml.2026.04.022","tag_type":"warning","value":"The paper's DOI indicates a 2026 publication date, which is in the future relative to most current literature — findings have not yet been widely peer-reviewed or cited.","value_numeric":null}],"summaries":{"what_studied":"This Phase 2 open-label study (BRIDGE) evaluated the pharmacokinetics (PK) of melphalan (the active alkylating metabolite of melflufen) and the safety of melflufen plus dexamethasone in 35 RRMM patients with moderate (eGFR 30–<45 mL/min/1.73 m²) or severe (eGFR 15–<30 mL/min/1.73 m²) renal impairment, across melflufen doses of 20–40 mg IV every 28 days.","key_result":"Melphalan exposure (Cmax and AUCinf) was lower at reduced doses: Cohort 1a (40 mg, moderate RI): Cmax 550.2 ng/mL, AUCinf 1418.7 h·ng/mL; Cohort 1b (30 mg, moderate RI): Cmax 472.2 ng/mL, AUCinf 1286.2 h·ng/mL; Cohort 2a (20 mg, severe RI): Cmax 181.2 ng/mL, AUCinf 528.5 h·ng/mL. Elimination half-life increased slightly with worsening renal function (89.1–109.6 min). TEAEs occurred in 34/35 patients; 6 patients died due to a TEAE.","limitations":"Very small cohort sizes (especially Cohort 2a, n=4) limit conclusions for severe RI. Only 3 post-infusion PK time points per cycle were collected, which may reduce PK model precision. No comparator arm with normal renal function was included within the study.","practice_takeaway":"For RRMM patients with moderate renal impairment, PK data support a melflufen dose of 30 mg (rather than 40 mg). No new safety signals were identified in patients with moderate-to-severe renal impairment, but the high TEAE mortality rate (6/35) warrants close monitoring."}},{"doi":"10.1007/s00467-025-07118-0","pmid":"41501260","title":"Efficacy of mycophenolate mofetil versus cyclophosphamide in the management of childhood-onset lupus nephritis: a systematic review and meta-analysis","journal_title":"Pediatric Nephrology","journal_issn":"0931-041X","published_at":"2026-01-08T00:00:00.000Z","url":"https://doi.org/10.1007/s00467-025-07118-0","source_score":8,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2026-01-13","doi":"10.1007/s00467-025-07118-0","days":"7","issn":"0931-041X","rank":"7","field":"Clinical Medicine","score":"8","category":"Urology & Nephrology","categories":["Urology & Nephrology"],"_categories":["Urology & Nephrology"]},"pubmed":{"doi":"10.1007/s00467-025-07118-0","title":"Efficacy of mycophenolate mofetil versus cyclophosphamide in the management of childhood-onset lupus nephritis: a systematic review and meta-analysis.","journal":"Pediatric nephrology (Berlin, Germany)","methods":"","results":"Out of 1,633 screened records, seven studies met the inclusion criteria, six observational studies (n = 282) and one RCT (n = 24). 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Am J Kidney Dis 70:324–336. https://doi.org/10.1053/j.ajkd.2016.12.008","article-title":null,"journal-title":"Am J Kidney Dis","doi-asserted-by":"publisher"}],"short-title":[],"update-policy":"https://doi.org/10.1007/springer_crossmark_policy","alternative-id":["7118"],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"original-title":[],"container-title":["Pediatric Nephrology"],"reference-count":37,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2026,1,8]]},"references-count":37,"short-container-title":["Pediatr Nephrol"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1007/s00467-025-07118-0","is_oa":false,"title":"Efficacy of mycophenolate mofetil versus cyclophosphamide in the management of childhood-onset lupus nephritis: a systematic review and meta-analysis","updated":"2026-01-10T04:46:20+00:00","published_date":"2026-01-08","best_oa_location":null}},"created_at":"2026-01-18T22:40:12.285Z","updated_at":"2026-01-20T15:55:50.695Z","tags":[{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"age_group","value":"pediatric","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"category","value":"Urology & Nephrology","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"condition","value":"Lupus Nephritis","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"generic","value":"mycophenolate mofetil","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"modality","value":"Antimetabolite","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"sample_size","value":"n=306","value_numeric":306},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"study_design","value":"Systematic Review and Meta-analysis","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"warning","value":"Heterogeneity metric (I2) is truncated/not reported in the abstract.","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"warning","value":"Publication bias could not be formally assessed due to the small number of studies.","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"warning","value":"Safety outcomes are described without numeric rates in the abstract.","value_numeric":null},{"paper_doi":"10.1007/s00467-025-07118-0","tag_type":"warning","value":"Study pool mixes observational studies with one small RCT, making design classification and certainty less clear.","value_numeric":null}],"summaries":{"what_studied":"A systematic review and meta-analysis compared mycophenolate mofetil (MMF) plus corticosteroids versus intravenous cyclophosphamide (IVCP) plus corticosteroids for induction therapy in children (≤17 years) with biopsy-proven proliferative lupus nephritis, searching six databases on June 2, 2025. Seven studies were included (six observational, n=282; one RCT, n=24).","key_result":"Across six observational studies (n=282), complete remission rates were similar between MMF and IVCP (pooled RR 1.01; 95% CI 0.78–1.29).","limitations":"Evidence was dominated by observational studies with only one small pediatric RCT at high risk of bias. Outcome definitions and baseline disease severity varied, and small study numbers limited subgroup analyses and assessment of publication bias.","practice_takeaway":"MMF appears to achieve similar induction efficacy as IVCP in pediatric proliferative lupus nephritis and is a reasonable alternative when appropriate. Larger multicenter pediatric RCTs are needed to confirm efficacy and guide definitive treatment choices."}},{"doi":"10.1002/art.70032","pmid":"41451470","title":"ANCA\n ‐Associated Vasculitides in Systemic Sclerosis: A Unique Clinical Overlap with Significant Implications for Treatment and Outcomes","journal_title":"Arthritis & Rheumatology","journal_issn":"2326-5191","published_at":"2025-12-26T00:00:00.000Z","url":"https://doi.org/10.1002/art.70032","source_score":7,"is_retracted":false,"is_open_access":false,"raw_metadata":{"ooir":{"day":"2025-12-31","doi":"10.1002/art.70032","days":"14","issn":"2326-5191","rank":"7","field":"Clinical Medicine","score":"7","category":"Rheumatology","categories":["Rheumatology"],"_categories":["Rheumatology"]},"pubmed":{"doi":"10.1002/art.70032","title":"ANCA-Associated Vasculitides in Systemic Sclerosis: A Unique Clinical Overlap with Significant Implications for Treatment and Outcomes.","journal":"Arthritis & rheumatology (Hoboken, N.J.)","methods":"","results":"We included 30 patients (median age 51.5 years, 83% female). SSc preceded AAV in all cases; 27% had diffuse cutaneous SSc, while 73% had limited cutaneous SSc. Anti-Scl70 antibodies were detected in 50%, and interstitial lung disease (ILD) was present in 80%, predominantly with a fibrosing non-specific interstitial pneumonia pattern (54%). AAV was microscopic polyangiitis in 90%, with MPO-ANCA positivity in 93%. Renal involvement was common (76%), with a median serum creatinine of 170 μmol/l (IQR 120-361) and proteinuria of 2 g/g (IQR 0.9-2.3). All patients received GCs in combination with cyclophosphamide (50%) or rituximab (47%). No cases of scleroderma renal crisis were observed. SSc manifestations, including ILD and skin involvement, remained stable during follow-up.","abstract":"$31","keywords":[],"pubmed_id":"41451470","conclusions":"AAV, predominantly microscopic polyangiitis with MPO-ANCA, can occur in SSc, particularly in patients with fibrosing ILD and anti-Scl70. Standard vasculitis treatments appear to be effective and do not worsen outcomes in SSc.","publication_date":"2025-12-26T00:00:00"},"crossref":{"DOI":"10.1002/art.70032","URL":"https://doi.org/10.1002/art.70032","ISSN":["2326-5191","2326-5205"],"link":[{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/art.70032","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":null,"score":1,"title":["ANCA\n ‐Associated Vasculitides in Systemic Sclerosis: A Unique Clinical Overlap with Significant Implications for Treatment and Outcomes"],"author":[{"given":"Deborah","family":"Eshagh","sequence":"first","affiliation":[{"name":"Department of Internal medicine Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP) F‐75014 Paris France"}]},{"given":"Thomas","family":"Quéméneur","sequence":"additional","affiliation":[{"name":"Centre Hospitalier Department of Internal medicine Valenciennes France"}]},{"given":"Alexandre","family":"Karras","sequence":"additional","affiliation":[{"name":"Department of Nephrology Georges Pompidou Hospital, APHP Paris France"}]},{"given":"Viviane","family":"Queyrel","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Centre Hospitalier Universitaire Nice France"}]},{"given":"Jean‐Francois","family":"Augusto","sequence":"additional","affiliation":[{"name":"Department of Nephrology Centre Hospitalier Universitaire Angers France"}]},{"given":"Christian","family":"Agard","sequence":"additional","affiliation":[{"name":"Nantes Université, CHU Nantes, Service de médecine interne F‐44000 Nantes France"}]},{"given":"Vincent","family":"Audard","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Transplantation Henri Mondor University Hospital, Univ Paris Créteil (APHP), Institute Mondor of Research Biomedical (IMRB) Créteil France"}]},{"given":"Alexandre","family":"Cez","sequence":"additional","affiliation":[{"name":"Department of Nephrology Tenon Hospital, APHP Paris France"}]},{"given":"Marion","family":"Couderc","sequence":"additional","affiliation":[{"name":"Department of Rhumatology Centre Hospitalier Universitaire, INSERM, IMosT, UMR 1240, Université d'Auvergne Clermont‐ferrand France"}]},{"given":"Pierre","family":"Duffau","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Centre Hospitalier Universitaire Bordeaux France"}]},{"given":"Cécile Audrey","family":"Durel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Hôpital Edouard Herriot Lyon France"}]},{"given":"Stanislas","family":"Faguer","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Organ Transplantation and National Referral Centre for Rare Kidney Diseases University Hospital of Toulouse France"}]},{"given":"Noémie","family":"Jourde‐Chiche","sequence":"additional","affiliation":[{"name":"Department of Nephrology Centre Hospitalier Universitaire Marseille France"}]},{"given":"Aurélie","family":"Lavergne","sequence":"additional","affiliation":[{"name":"Department of Nephrology Centre Hospitalier Universitaire Rennes France"}]},{"given":"Christian","family":"Lavigne","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Centre de référence des Maladies Auto‐Immunes et Auto‐inflammatoires Systémiques rares de l'Adulte du Nord, Nord‐Ouest, Méditerranée et Guadeloupe, site d'Angers (CeRAINOM‐Angers) Centre Hospitalier Universitaire Angers France"}]},{"given":"Nicolas","family":"Limal","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Henri Mondor Hospital, APHP Créteil France"}]},{"given":"Rafik","family":"Mesbah","sequence":"additional","affiliation":[{"name":"Department of Nephrology Centre Hospitalier, Boulogne sur Mer France"}]},{"given":"Amélie","family":"Servettaz","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Centre Hospitalier Universitaire Reims France"}]},{"given":"Carole","family":"Philipponnet","sequence":"additional","affiliation":[{"name":"Department of Nephrology Centre Hospitalier Universitaire Clermont Ferrand France"}]},{"given":"Perrine","family":"Smets","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Centre Hospitalier Universitaire Clermont Ferrand France"}]},{"given":"Theophile","family":"Hubsch","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Hopital d'instruction des Armées Saint Anne Toulon France"}]},{"given":"Benjamin","family":"Chaigne","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP) F‐75014 Paris France"}]},{"given":"Alexis","family":"Régent","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP) F‐75014 Paris France"}]},{"given":"Xavier","family":"Puéchal","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP) F‐75014 Paris France"}]},{"given":"Luc","family":"Mouthon","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP) F‐75014 Paris France"}]},{"given":"Benjamin","family":"Terrier","sequence":"additional","affiliation":[{"name":"Department of Internal medicine Cochin Hospital, Assistance Publique‐Hôpitaux de Paris (AP‐HP) F‐75014 Paris France"}]},{"given":null,"family":null,"sequence":"additional","affiliation":[]}],"issued":{"date-parts":[[2025,12,26]]},"member":"311","prefix":"10.1002","source":"Crossref","volume":null,"archive":["Portico"],"created":{"date-time":"2025-12-26T09:42:01Z","timestamp":1766742121000,"date-parts":[[2025,12,26]]},"indexed":{"date-time":"2025-12-26T09:46:40Z","timestamp":1766742400264,"date-parts":[[2025,12,26]]},"license":[{"URL":"http://onlinelibrary.wiley.com/termsAndConditions#vor","start":{"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000,"date-parts":[[2025,12,26]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$32","language":"en","relation":{},"resource":{"primary":{"URL":"https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.70032"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"publication_history","label":"Publication 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Rheumatology"],"reference-count":0,"published-online":{"date-time":null,"timestamp":null,"date-parts":[[2025,12,26]]},"references-count":0,"short-container-title":["Arthritis & Rheumatology"],"is-referenced-by-count":0},"unpaywall":{"doi":"10.1002/art.70032","is_oa":false,"title":"ANCA\n ‐Associated Vasculitides in Systemic Sclerosis: A Unique Clinical Overlap with Significant Implications for Treatment and Outcomes","updated":"2025-12-27T00:44:22+00:00","published_date":"2025-12-26","best_oa_location":null}},"created_at":"2026-01-14T18:30:49.575Z","updated_at":"2026-01-14T18:30:49.575Z","tags":[{"paper_doi":"10.1002/art.70032","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"category","value":"Rheumatology","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"condition","value":"ANCA-Associated Vasculitis","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"condition","value":"Systemic Sclerosis","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"generic","value":"cyclophosphamide","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"generic","value":"rituximab","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"level_of_evidence","value":"6","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"modality","value":"Alkylating Agent","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"modality","value":"Anti-CD20 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"modality","value":"Glucocorticoid","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"sample_size","value":"n=30","value_numeric":30},{"paper_doi":"10.1002/art.70032","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"study_design","value":"Case Series","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"warning","value":"Design classification may be interpreted as either a case series or a retrospective cohort; abstract reports a multicenter retrospective study without a comparator group.","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"warning","value":"Findings are from abstract-level data; full-text details (e.g., remission rates, survival) are not provided.","value_numeric":null},{"paper_doi":"10.1002/art.70032","tag_type":"warning","value":"Primary endpoints and follow-up duration are not specified in the abstract.","value_numeric":null}],"summaries":{"what_studied":"A multicenter retrospective study across 18 French centers described phenotype, management, and outcomes in patients meeting ACR/EULAR criteria for both systemic sclerosis and ANCA-associated vasculitis.","key_result":"Among 30 patients (median age 51.5, 83% female), AAV was microscopic polyangiitis in 90% with MPO-ANCA positivity in 93%. Renal involvement occurred in 76% with median creatinine 170 μmol/l (IQR 120–361) and proteinuria 2 g/g (IQR 0.9–2.3). All received glucocorticoids with cyclophosphamide (50%) or rituximab (47%); no scleroderma renal crisis was observed, and SSc ILD and skin involvement remained stable during follow-up.","limitations":"Retrospective design with small sample size (n=30). Follow-up duration and predefined primary outcomes were not reported.","practice_takeaway":"In SSc patients with overlapping AAV—most often MPO-positive microscopic polyangiitis—standard vasculitis regimens (glucocorticoids plus cyclophosphamide or rituximab) were used without observed scleroderma renal crisis, and SSc manifestations stayed stable during follow-up."}},{"doi":"10.1186/s40164-025-00729-1","pmid":"41437395","title":"Efficacy of melflufen in multiple myeloma with mutated or deleted TP53","journal_title":"Experimental Hematology & Oncology","journal_issn":"2162-3619","published_at":"2025-12-24T00:00:00.000Z","url":"https://doi.org/10.1186/s40164-025-00729-1","source_score":33,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2025-12-25","doi":"10.1186/s40164-025-00729-1","days":"30","issn":"2162-3619","rank":"10","field":"Clinical Medicine","score":"33","category":"Hematology","categories":["Hematology"],"_categories":["Hematology"]},"pubmed":{"doi":"10.1186/s40164-025-00729-1","title":"Efficacy of melflufen in multiple myeloma with mutated or deleted TP53.","journal":"Experimental hematology & oncology","methods":"","results":"","abstract":"Patients with multiple myeloma bearing a deletion of chromosome 17p (del(17p)), mutation of TP53, or both have poorer prognosis compared to patients without these aberrations. We investigated the activity and mechanism of melflufen (melphalan flufenamide) in myeloma models with wild type TP53 (TP53wt) and complete TP53 deletion (TP53","keywords":["TP53 mutation","Clinical efficacy","In vitro efficacy","Melflufen","PFS","SoC alkylators","del(17p)"],"pubmed_id":"41437395","conclusions":"","publication_date":"2025-12-24T00:00:00"},"crossref":{"DOI":"10.1186/s40164-025-00729-1","URL":"https://doi.org/10.1186/s40164-025-00729-1","ISSN":["2162-3619"],"link":[{"URL":"https://link.springer.com/content/pdf/10.1186/s40164-025-00729-1.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/article/10.1186/s40164-025-00729-1","content-type":"text/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https://link.springer.com/content/pdf/10.1186/s40164-025-00729-1.pdf","content-type":"application/pdf","content-version":"vor","intended-application":"similarity-checking"}],"page":null,"type":"journal-article","issue":"1","score":1,"title":["Efficacy of melflufen in multiple myeloma with mutated or deleted TP53"],"author":[{"given":"Klara","family":"Acs","sequence":"first","affiliation":[]},{"given":"Juho J.","family":"Miettinen","sequence":"additional","affiliation":[]},{"given":"Philipp","family":"Sergeev","sequence":"additional","affiliation":[]},{"given":"Tobias","family":"Heckel","sequence":"additional","affiliation":[]},{"given":"Yumei","family":"Diao","sequence":"additional","affiliation":[]},{"given":"Kristina","family":"Witt-Mulder","sequence":"additional","affiliation":[]},{"given":"Marcus","family":"Thureson","sequence":"additional","affiliation":[]},{"given":"Thorsten","family":"Bischler","sequence":"additional","affiliation":[]},{"given":"Maiju-Emilia","family":"Huppunen","sequence":"additional","affiliation":[]},{"given":"Minna","family":"Suvela","sequence":"additional","affiliation":[]},{"given":"Jakob","family":"Obermüller","sequence":"additional","affiliation":[]},{"given":"Umair","family":"Munawar","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Slipicevic","sequence":"additional","affiliation":[]},{"given":"Ralf C.","family":"Bargou","sequence":"additional","affiliation":[]},{"given":"Fredrik","family":"Lehmann","sequence":"additional","affiliation":[]},{"given":"Stefan Svensson","family":"Gelius","sequence":"additional","affiliation":[]},{"given":"Stefan","family":"Norin","sequence":"additional","affiliation":[]},{"given":"Fredrik","family":"Schjesvold","sequence":"additional","affiliation":[]},{"given":"Pieter","family":"Sonneveld","sequence":"additional","affiliation":[]},{"given":"Thorsten","family":"Stühmer","sequence":"additional","affiliation":[]},{"given":"Caroline A.","family":"Heckman","sequence":"additional","affiliation":[]}],"funder":[{"id":[{"id":"10.13039/501100008413","id-type":"DOI","asserted-by":"publisher"}],"DOI":"10.13039/501100008413","name":"Instrumentariumin Tiedesäätiö","doi-asserted-by":"publisher"},{"name":"Oncopeptides"}],"issued":{"date-parts":[[2025,12,23]]},"member":"297","prefix":"10.1186","source":"Crossref","volume":"14","created":{"date-time":"2025-12-23T13:25:47Z","timestamp":1766496347000,"date-parts":[[2025,12,23]]},"indexed":{"date-time":"2025-12-23T13:28:50Z","timestamp":1766496530975,"date-parts":[[2025,12,23]]},"license":[{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000,"date-parts":[[2025,12,23]]},"delay-in-days":0,"content-version":"tdm"},{"URL":"https://creativecommons.org/licenses/by/4.0","start":{"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000,"date-parts":[[2025,12,23]]},"delay-in-days":0,"content-version":"vor"}],"subject":[],"abstract":"$33","language":"en","relation":{},"resource":{"primary":{"URL":"https://link.springer.com/10.1186/s40164-025-00729-1"}},"subtitle":[],"assertion":[{"name":"received","group":{"name":"ArticleHistory","label":"Article History"},"label":"Received","order":1,"value":"11 August 2025"},{"name":"accepted","group":{"name":"ArticleHistory","label":"Article History"},"label":"Accepted","order":2,"value":"22 November 2025"},{"name":"first_online","group":{"name":"ArticleHistory","label":"Article History"},"label":"First Online","order":3,"value":"23 December 2025"},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"},"order":1},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"},"order":2,"value":"Bone marrow (BM) aspirates were collected from multiple myeloma (MM) patients after informed consent using protocols approved by the ethical committee of Helsinki University Hospital (Ethical Committee Statement 303/13/03/01/201, latest amendment 7 dated 15 June 2016; latest HUS study permit HUS/395/2018 dated 13 February 2018; Permit numbers 239/13/03/00/2010, 303/13/03/01/2011) and in accordance with the Declaration of Helsinki."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"},"order":3,"value":"Not applicable."},{"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"},"order":4,"value":"$34"}],"deposited":{"date-time":"2025-12-23T13:25:49Z","timestamp":1766496349000,"date-parts":[[2025,12,23]]},"issn-type":[{"type":"electronic","value":"2162-3619"}],"published":{"date-parts":[[2025,12,23]]},"publisher":"Springer Science and Business Media LLC","reference":[{"DOI":"10.3390/ijms21010013","key":"729_CR1","year":null,"issue":null,"author":null,"volume":null,"first-page":null,"unstructured":"Ho T, Tan BX, Lane D. 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The study was industry funded with multiple authors employed by the sponsor, which may bias analyses.","practice_takeaway":"For RRMM with del(17p), melflufen+dexamethasone yielded longer PFS and higher ORR than pomalidomide+dexamethasone in a post‑hoc analysis; preclinical work showed activity irrespective of TP53 status. Apply cautiously given the subgroup design and funding-related bias risk."}}],"initialOffset":16,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"modality","value":"Alkylating Agent"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Modalities","href":"/hub/tag/modality"},{"name":"Alkylating Agent"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"modality","hub_tag_value":"Alkylating Agent"}}}]]

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