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:T456,To provide updated guidance regarding the therapy for multiple myeloma. ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature. The updated review identified a total of 161 relevant randomized trials. Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles.Additional information is available at www.asco.org/hematologic-malignancies-guidelines.31:Tff6, ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the

ASCO Guidelines Methodology Manual

. ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more . PURPOSE To provide updated guidance regarding the therapy for multiple myeloma. METHODS ASCO and Ontario Health (Cancer Care Ontario) convened a joint Expert Panel and conducted an updated systematic review of the literature. RESULTS The updated review identified a total of 161 relevant randomized trials. UPDATED RECOMMENDATIONS Daratumumab therapy may be offered to patients with high-risk smoldering myeloma. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as initial therapy for transplant eligible patients. They should also be offered at least lenalidomide maintenance, with or without daratumumab, carfilzomib, and/or dexamethasone. Quadruplet therapy with daratumumab or isatuximab, combined with bortezomib, lenalidomide, and dexamethasone, should be offered as therapy for suitable transplant-ineligible patients. Patients with relapsed or refractory multiple myeloma should be offered triplet therapy or T-cell redirecting therapies according to a set of recommended principles. Additional information is available at www.asco.org/hematologic-malignancies-guidelines . 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Smoldering Multiple Myeloma: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Smoldering Multiple Myeloma (condition). Clinician-written summaries and actionable practice insights. 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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":"10.1182/blood.2025032630","pmid":"42413006","title":"Single Cell Analysis of the Tumor Microenvironment Landscape Across the Disease Spectrum of Multiple Myeloma","journal_title":"Blood Journal","journal_issn":"0006-4971","published_at":"2026-07-07T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025032630","source_score":38,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-16T13:37:20.452Z","updated_at":"2026-07-16T13:37:20.452Z","tags":[{"paper_doi":"10.1182/blood.2025032630","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"condition","value":"Monoclonal Gammopathy of Undetermined Significance","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"condition","value":"Smoldering Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"modality","value":"Immunotherapy","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"sample_size","value":"n=235","value_numeric":235},{"paper_doi":"10.1182/blood.2025032630","tag_type":"study_design","value":"Single-Cell Transcriptomic Analysis / Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"warning","value":"Precursor states (MGUS, SMM) are implied in the disease spectrum but not explicitly named in the abstract — tagging reflects reasonable inference from 'precursor states' language.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"warning","value":"Study design is a hybrid single-cell atlas/cohort study; no standard canonical label fully captures it. Labeled as single-cell transcriptomic analysis with retrospective cohort elements.","value_numeric":null},{"paper_doi":"10.1182/blood.2025032630","tag_type":"warning","value":"The study design is primarily observational/cross-sectional; 'practice_changing' flag reflects the novelty and clinical framing of the ecotype framework, but prospective validation is explicitly lacking. Clinicians should interpret ecotype-outcome associations cautiously until validated in independent cohorts.","value_numeric":null}],"summaries":{"what_studied":"This study mapped the tumor microenvironment (TME) across the full multiple myeloma (MM) disease spectrum — from precursor states to active disease — using integrated single-cell RNA, T-cell receptor, and B-cell receptor sequencing from bone marrow samples of 235 patients.","key_result":"Five reproducible TME 'ecotypes' were identified via non-negative matrix factorization. One ecotype enriched for bone marrow-resident populations with limited immune infiltration was linked to tumor expansion and worse clinical outcomes; ecotypes defined by T-cell functional states showed distinct associations with immunotherapy response and survival.","limitations":"Single time-point bone marrow sampling limits longitudinal tracking of TME evolution; treatment heterogeneity across the cohort may confound ecotype-outcome associations; findings are observational and require prospective validation before clinical application.","practice_takeaway":"TME ecotype classification — particularly identifying the immune-cold, bone marrow-resident ecotype — may help stratify MM patients by prognosis and guide selection of immunotherapy strategies. Ecotype-targeted or stage-specific immunotherapy approaches warrant prospective evaluation."}},{"doi":"10.1182/blood.2025029422","pmid":"42247308","title":"IRF2 is an essential transcription factor with pathogenic and prognostic impact in multiple myeloma","journal_title":"Blood","journal_issn":"0006-4971","published_at":"2026-06-25T00:00:00.000Z","url":"https://doi.org/10.1182/blood.2025029422","source_score":56,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-03T13:38:59.206Z","updated_at":"2026-07-03T13:38:59.206Z","tags":[{"paper_doi":"10.1182/blood.2025029422","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"condition","value":"Monoclonal Gammopathy of Undetermined Significance","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"condition","value":"Smoldering Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"modality","value":"CRISPR-Cas9 Screening","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"modality","value":"Transcription Factor Inhibition","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"study_design","value":"Translational/Basic Science Study","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"warning","value":"No specific hazard ratios, median survival times, or sample sizes for the prognostic cohorts are reported in the abstract — key_result is based on directional findings only.","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"warning","value":"Study design is primarily preclinical/translational; the level of evidence (3) reflects the prognostic cohort analyses, not the mechanistic experiments.","value_numeric":null},{"paper_doi":"10.1182/blood.2025029422","tag_type":"warning","value":"The impact_flag 'practice_changing' is applied cautiously here: IRF2 has prognostic value, but no approved therapeutic targeting IRF2 in MM currently exists; the flag reflects potential paradigm shift in biomarker use rather than immediate clinical practice change.","value_numeric":null}],"summaries":{"what_studied":"This study used CRISPR-Cas9 library screening in multiple myeloma (MM) cells to identify essential transcription factors (TFs), then functionally characterized IRF2 — its chromatin binding, role in cell survival and migration, transcriptional activity in precursor conditions (MGUS, SMM), and prognostic impact on PFS and OS.","key_result":"IRF2 was identified as a critical MM transcription factor; it suppresses necroptosis and promotes cell migration. Higher IRF2 expression was independently associated with worse progression-free survival (PFS) and overall survival (OS) in both univariate and multivariate analyses, after adjusting for common MM genetic risk factors.","limitations":"The study is largely mechanistic and genomic; clinical prognostic analyses lack reported hazard ratios or absolute survival differences. Therapeutic targeting of IRF2 has not yet been tested in vivo or in patients.","practice_takeaway":"IRF2 expression level may serve as an independent prognostic marker in MM — higher expression signals worse outcomes even after accounting for established genetic risk factors. While not yet actionable therapeutically, it warrants consideration as a biomarker in prognostic workups and is a candidate target for future drug development."}},{"doi":"10.1038/s41375-026-02979-2","pmid":"42086933","title":"Smoldering multiple myeloma in transition: redefining early myeloma in the modern era","journal_title":"Leukemia","journal_issn":"0887-6924","published_at":"2026-05-05T00:00:00.000Z","url":"https://doi.org/10.1038/s41375-026-02979-2","source_score":10,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-14T13:22:49.680Z","updated_at":"2026-05-14T13:22:49.680Z","tags":[{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"brand","value":"Darzalex","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"condition","value":"Monoclonal Gammopathy","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"condition","value":"Smoldering Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"generic","value":"daratumumab","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"level_of_evidence","value":"7","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"modality","value":"Anti-CD38 Monoclonal Antibody","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"warning","value":"Sample size tag omitted — no study population is reported in this review article.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"warning","value":"Sex of the patient population is not reported or applicable in this review context.","value_numeric":null},{"paper_doi":"10.1038/s41375-026-02979-2","tag_type":"warning","value":"This is a narrative review without primary data; key claims about reclassification of SMM are speculative and forward-looking.","value_numeric":null}],"summaries":{"what_studied":"This review examines the evolving classification, risk stratification, and treatment paradigm for smoldering multiple myeloma (SMM), with a focus on how advances in molecular biology, imaging, and immunotherapy — including the recent FDA approval of daratumumab for high-risk SMM — are reshaping the boundary between SMM and active multiple myeloma (MM).","key_result":"The FDA approval of daratumumab for high-risk SMM marks the first clinically validated early intervention in this setting, challenging the traditional 'watch-and-wait' approach and raising the possibility that future reclassification may eliminate SMM as a distinct diagnostic category.","limitations":"As a narrative review, no primary data or clinical outcomes are reported; conclusions are largely conjecture-based and dependent on technologies and reclassification criteria that are not yet fully defined.","practice_takeaway":"Clinicians should recognize that high-risk SMM now has an FDA-approved treatment option (daratumumab), and the classic watch-and-wait approach is no longer the only standard. Re-evaluation of SMM risk stratification using modern imaging and molecular tools is increasingly important in practice."}},{"doi":"10.1038/s41408-026-01486-y","pmid":"42067559","title":"A differentiated effector T cell repertoire defines a functionally high-risk group of smoldering myeloma patients","journal_title":"Blood Cancer Journal","journal_issn":"2044-5385","published_at":"2026-05-01T00:00:00.000Z","url":"https://doi.org/10.1038/s41408-026-01486-y","source_score":15,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-07T22:50:15.571Z","updated_at":"2026-05-07T22:50:15.571Z","tags":[{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"category","value":"Hematology","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"condition","value":"Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"condition","value":"Smoldering Multiple Myeloma","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"level_of_evidence","value":"4","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"modality","value":"Machine Learning / Random Forest Classifier","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"modality","value":"Plasma Proteomics","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"modality","value":"Spectral Flow Cytometry","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"sample_size","value":"n=18","value_numeric":18},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"study_design","value":"Exploratory Cohort Study","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"warning","value":"Extremely small sample size (n=9 per group) limits statistical power; all findings are exploratory and hypothesis-generating only.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"warning","value":"Study design is retrospective and single-center (MSKCC); results may not generalize to broader SMM populations.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"warning","value":"Study design was labeled 'Correspondence' in the journal, indicating it was not a full original research article — depth of methodological reporting may be limited.","value_numeric":null},{"paper_doi":"10.1038/s41408-026-01486-y","tag_type":"warning","value":"The random forest model was trained and tested on the same small cohort with cross-validation only — independent external validation is absent.","value_numeric":null}],"summaries":{"what_studied":"Peripheral blood (PB) immune profiling using high-dimensional spectral cytometry and plasma proteomics (Olink) was performed in 18 Mayo 2/20/20 risk-matched SMM patients (9 early progressors [EP] with median time to progression 2.1 years vs. 9 non-progressors [NP] with median follow-up 8.6 years) to identify T cell signatures predictive of early progression to active multiple myeloma.","key_result":"EP patients showed a 4.3-fold enrichment in CD8+ T-EMRA cells (high CD57/TOX; p=0.018) and a 7.6-fold enrichment in CD4+ T-EMRA cells (p=0.045) vs. NP patients. A random forest model using Granzyme B, CD272 (BTLA), Granzyme K, and CD45RA achieved 75% accuracy (F1: 0.76 NP, 0.74 EP) in predicting progression. Plasma IL-18 and MMP-1 were ~2-fold higher in EP patients (p=0.0037 and p=0.0065, respectively).","limitations":"- Very small sample size (n=18 total; n=9 per group), making findings exploratory and prone to overfitting.\n- Retrospective, single-center design (MSKCC) limits generalizability.\n- Prospective validation in larger cohorts is needed before clinical application.","practice_takeaway":"A focused flow cytometry panel measuring Granzyme B, CD272, Granzyme K, and CD45RA on peripheral blood may help identify SMM patients at high risk of early progression beyond standard tumor-burden scores. 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