A summary of some notable key multiple myeloma research from September-October 2026   
 

Scope and Methodology    
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from September-October 2026. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, clinical updates, reviews, letters to the editor, correspondence, and the latest results of ongoing clinical trials. It is intended for patients, care partners, and oncology professionals. This blog article was medically reviewed by Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO, on October 28, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.    

   
Guidelines & Recommendations

American Society of Hematology 2026 guidelines for diagnosis of iron deficiency — Blood Advances (September 2026)

What is the purpose of these guidelines? 
To develop evidence-based guidelines from the American Society of Hematology (ASH) to support the diagnosis of iron deficiency across populations and settings, including guidance on diagnostic thresholds and inflammation.

Summary 
ASH convened a multidisciplinary guideline panel, including a patient representative, and used systematic evidence reviews and the GRADE approach to develop recommendations through July 2025. The panel made 5 recommendations, including population-specific serum ferritin thresholds, considerations for alternative diagnostic thresholds, and guidance for diagnosing iron deficiency in people with inflammation.

Strengths  
Multidisciplinary panel; included a patient representative; used systematic evidence reviews and the GRADE approach; recommendations underwent public comment.

Limitations/Gaps 
The panel identified gaps in the literature and research priorities.

Why these guidelines matter 
The guidelines provide evidence-based recommendations for diagnosing iron deficiency, with serum ferritin thresholds tailored to specific populations and guidance for cases involving inflammation. The panel also identified areas where additional research is needed.

Reference: 
Jacquelyn M Powers, Ming Yeong Lim, Maureen O. Achebe, Imo J Akpan, Michael Auerbach, Megan C Brown, Maria Paula Cardenas, Caroline Cromwell, Thomas G. DeLoughery, Robert E. Fleming, Martina Fraga, George Goshua, Paula D. James, Adam K Lewkowitz, Jori Ellen May, Grace Nnadozie, Frances Ogunnaya, Guillermo J. Ruiz-Arguelles, Michelle Sholzberg, Layla Van Doren, Angela C. Weyand, Michelle Paula Zeller, Muayad Azzam, Ali Choaib, Qais Hamarsha, Hassan Kawtharany, Jana Khawandi, Reem A. Mustafa; American Society of Hematology 2026 guidelines for diagnosis of iron deficiency. Blood Adv 2026; bloodadvances.2025015950. doi: https://doi.org/10.1182/bloodadvances.2025015950

Review

Next Generation Sequencing in the Diagnosis of Multiple Myeloma — Frontiers in Bioscience Scholar (September 2026)

What is the purpose of the review? 
This review summarizes current evidence on the use of next-generation sequencing (NGS), including whole-exome sequencing (WES), whole-genome sequencing (WGS), and targeted gene panels, for diagnosis, prognostic assessment, molecular characterization, and minimal residual disease (MRD) monitoring in multiple myeloma (MM). It also examines how genomic profiling and NGS-based MRD assessment may inform risk stratification and treatment monitoring.

Summary 
The review describes recurrent genomic alterations in MM, including TP53, KRAS, NRAS, DIS3, FAM46C, BRAF, and other genes, and summarizes evidence linking genomic features with disease biology, prognosis, clonal evolution, and treatment resistance. Across the cited studies, NGS-based MRD assays demonstrated high sensitivity and specificity, with MRD negativity associated with longer progression-free survival (PFS) and overall survival (OS); comparative studies reported detection limits as low as 0.001% (10⁻⁵) and strong concordance with flow cytometry and PCR-based methods. WGS, WES, and targeted panels such as myTYPE provided complementary information on mutations, copy-number abnormalities, structural variants, clonotypes, and molecular subgroups.

Key points

Genomic characterization 
• WES studies repeatedly identified alterations involving TP53, KRAS, NRAS, DIS3, FAM46C, BRAF, and other genes. 
• In studies cited in the review, reported alteration frequencies included KRAS/NRAS 36%, TP53 28%, DIS3 20%, FAM46C 16%, and TRAF3 12% in one cohort. 
• WGS/WES identified clinically relevant abnormalities, including t(4;14), t(6;14), t(11;14), t(14;16), t(14;20), hyperhaploidy, and biallelic TP53 inactivation.

NGS-based MRD 
• NGS detects residual clonal disease at very low levels and can assess clonal evolution over time. 
• In one comparison, NGS and next-generation flow cytometry (NGF) detected MRD in 92% and 89% of cases, respectively; detection limits were 0.01% for NGS versus 0.1% for NGF. 
• A standardized NGS MRD assay reported 0.001% sensitivity and 100% specificity in studies involving 40 and 166 MM patients. 
• MRD negativity was consistently associated in the cited studies with improved PFS and OS.

Comparisons with other methods 
• NGS showed high concordance with flow cytometry and PCR-based methods, while several cited studies reported greater sensitivity for low-level MRD. 
• Yao et al. (2021) reported MRD detection in 45/50 (90%) patients by NGS versus 43/50 (86%) by real-time qPCR, with a correlation coefficient of 0.92. 
• Rustad et al. (2020) reported 95.2% sensitivity and 100% specificity, with κ = 0.85, for NGS MRD detection in bone marrow samples.

Targeted panels 
• The myTYPE panel was evaluated for clonotype detection and genomic characterization. 
• Studies reported concordance between myTYPE and WGS for several copy-number alterations, including deletions of 1p, 13q, 16q, and 17p and gains of 1q and 11q. 
• The review explicitly notes the need for validation in larger clinical cohorts.

Limitations/future needs 
• MRD testing is not yet universally available. 
• Further research is needed to optimize MRD assessment and integrate it into treatment decision-making. 
• The review identifies standardization, biomarker validation, and prospective evaluation of sequencing-informed strategies as areas requiring further work.

Why this review matters 
The reviewed evidence indicates that NGS can characterize genomic alterations and clonal architecture in MM and can be used for sensitive MRD detection and monitoring. NGS-based MRD assessment was associated with clinical outcomes in the cited studies, while WES, WGS, and targeted panels provided complementary genomic information; the review identifies standardization, biomarker validation, and prospective clinical evaluation as remaining needs.

Reference: 
Ikram EL Fazazi, Hajar Ihlal, Amal Ouskri, Samira Nmer, Angela Washenko, Hinde EL Mouhi, Meriame Abbassi, Mohamed Ahakoud, Laila Bouguenouch, Rhizlane Berrady, Karim Ouldim, Mohammed El-Azami-El-Idrissi. Next Generation Sequencing in the Diagnosis of Multiple Myeloma. Front. Biosci. (Schol Ed) 2026, 18(3), 44690. https://doi.org/10.31083/FBS44690 (registering DOI)

Extracorporeal Free-Light-Chain Removal in Myeloma Cast Nephropathy: Plasma Exchange and Hemodialysis Strategies in the Era of Effective Antimyeloma Therapy — Journal of Clinical Medicine (September 2026)

What is the purpose of the review? 
To evaluate whether extracorporeal removal of circulating serum free light chains (sFLCs) provides additional renal benefit in multiple myeloma with light-chain cast nephropathy in the era of effective antimyeloma therapy. It examines randomized trials, newer extracorporeal approaches, contemporary daratumumab-containing regimens, and priorities for future prospective research.

Summary 
Renal impairment occurs in up to half of patients with newly diagnosed multiple myeloma, with approximately 2–4% requiring dialysis at presentation, most commonly because of light-chain cast nephropathy. Randomized trials of plasma exchange and high-cutoff hemodialysis, including MYRE and EuLITE, did not demonstrate benefit for their primary renal endpoints; EuLITE reported more pulmonary infections with high-cutoff dialysis. The review concludes that conventional high-flux hemodialysis, when dialysis is indicated, combined with prompt antimyeloma therapy remains the evidence-based standard, while the potential role of enhanced sFLC removal remains unresolved and requires randomized evaluation using contemporary treatment regimens.

Key points 
• Randomized evidence: MYRE (98 patients) and EuLITE (90 patients) found no benefit from high-cutoff hemodialysis for their primary renal endpoints; pooled analysis found no survival benefit.

• Safety: EuLITE reported more pulmonary infections in the high-cutoff arm. High-cutoff membranes can cause albumin depletion, calcium and magnesium wasting, immunoglobulin loss, and potential drug removal.

• Contemporary therapy: In a small frontline series, daratumumab-containing regimens produced >50% sFLC reduction in every patient at a median of 3 days.

• Newer membranes: Medium-cutoff membranes, polymethylmethacrylate adsorptive dialyzers, and hemodiafiltration with endogenous reinfusion have produced substantial sFLC reductions with less albumin loss in small uncontrolled series, but none has been compared with conventional dialysis in a randomized trial.

• Potential research populations: Anuria or oliguria, very high circulating sFLC burden, chemoresistant disease, or inability to receive daratumumab-containing therapy are proposed as hypotheses for future trials; no validated sFLC threshold or kinetic criterion defines these groups.

• Strength: The review identifies established management measures, including monitored hydration, correction of hypercalcemia, avoidance of NSAIDs and non-essential iodinated contrast, and prompt bortezomib-based chemotherapy with high-dose dexamethasone.

• Limitation: Existing studies differ in patient populations, biopsy requirements, chemotherapy regimens, and renal-response definitions, limiting direct comparison and extrapolation to contemporary practice.

• Ongoing research: ECOG-ACRIN EAA241 (NCT07085728) is a randomized phase 2 trial evaluating daratumumab-hyaluronidase–bortezomib–dexamethasone versus cyclophosphamide–bortezomib–dexamethasone in newly diagnosed multiple myeloma with light-chain cast nephropathy and new-onset renal failure.

Why this review matters 
This narrative review states that conventional high-flux hemodialysis, initiated for conventional dialysis indications and combined with immediate antimyeloma therapy, is the current standard kidney-replacement modality for myeloma cast nephropathy. The clinical benefit of enhanced extracorporeal sFLC removal has not been established, and determining whether selected patients benefit requires randomized trials using contemporary antimyeloma therapy; proposed selection criteria remain unvalidated hypotheses rather than recommendations for current practice.

Reference: 
Gembillo, G., Soraci, L., Lo Cicero, L., Terzo, C., Casuscelli, C., Cuzzola, F., Sudano, F., Ricca, M. F., Scapellato, M., Messina, R., La Spada, A., Sharma, A., & Santoro, D. (2026). Extracorporeal Free-Light-Chain Removal in Myeloma Cast Nephropathy: Plasma Exchange and Hemodialysis Strategies in the Era of Effective Antimyeloma Therapy. Journal of Clinical Medicine, 15(18), 7211. https://doi.org/10.3390/jcm15187211

Diagnostic challenges posed by the wide morphological and immunophenotypic spectrum of plasma cell neoplasms — Blood Research (October 2026)

What is the purpose of the review? 
To describe rare morphological and immunophenotypic variants of plasma cell neoplasms (PCNs), particularly multiple myeloma (MM), that can create diagnostic difficulties. It focuses on distinguishing these variants from other hematologic malignancies and reactive conditions using morphology, immunophenotyping, molecular studies, and clinical findings.

Summary 
PCNs can show uncommon morphological patterns, including small-cell, plasmablastic, and pleomorphic/anaplastic variants, as well as extramedullary disease (EMD) and plasma cell leukemia (PCL), that may resemble B-cell or T-cell lymphomas and other malignancies. The review describes specific diagnostic findings, including CD19, CD45, CD56, CD117, CD3, CD4, cyclin D1, EBV status, MYD88 L265P mutation, and FISH abnormalities, while emphasizing that no single finding is sufficient in several challenging differential diagnoses. Accurate classification requires integration of morphology, immunophenotyping, molecular studies, and clinical correlation.

Key points

Small-cell variant of MM 
• Identified in 12 of 351 MM cases (3.4%) in one cited study. 
• May strongly express CD20 and cyclin D1 and mimic mantle cell lymphoma (MCL). 
• Differentiation from lymphoplasmacytic lymphoma (LPL) may require assessment of lytic bone lesions, MYD88 L265P mutation, serum free light-chain ratio, immunophenotype, and clinical findings. 
• LPL has a MYD88 L265P mutation in approximately 95% of cases.

Plasmablastic variant 
• Plasmablastic myeloma (PBM) and plasmablastic lymphoma (PBL) can have nearly identical morphology and immunophenotypes. 
• Myeloma-defining features supporting PBM include extensive marrow involvement (≥60% plasmablasts), serum free light-chain ratio ≥100, CRAB features, and serum M protein. 
• EBV positivity alone does not distinguish PBM from PBL.

Pleomorphic/anaplastic MM 
• Described as a very rare variant characterized by marked cytologic atypia, including multinucleated or multilobated nuclei. 
• It may occur at initial presentation or after transformation/dedifferentiation at relapse and is often associated with extramedullary sites.

Extramedullary disease 
• EMD is defined as clonal PCs outside the bone marrow and occurs in approximately 7%–18% of patients with MM. 
• It is more frequent with plasmablastic and pleomorphic morphology and among patients with relapsed MM. 
• In a cited study of 25 PBM cases, 15 (60%) had EMD; soft tissue and/or skin accounted for 10 of 15 cases (67%).

Plasma cell leukemia 
• The International Myeloma Working Group revised the diagnostic definition in 2021 to ≥5% circulating PCs in peripheral blood in patients otherwise meeting criteria for symptomatic MM. 
• Primary PCL accounts for approximately 60%–70% of PCL cases. 
• In one cited cohort of 53 Turkish patients, primary PCL had a median progression-free survival of 4 months. 
• Secondary PCL develops during MM progression or relapse and occurs in approximately 1% of MM cases during the disease course.

Immunophenotypic challenges 
• Neoplastic PCs usually lose CD19 expression; more than 95% of cases reportedly lack CD19. 
• CD56 is expressed in approximately 60%–80% of MM cases, but leukemic PCs in primary and secondary PCL are usually CD56-negative. 
• Aberrant expression of CD117, CD3, CD4, cyclin D1, EMA, or cytokeratin can create diagnostic pitfalls. 
• CD45 expression occurs in up to 14% of MM cases, so CD45 positivity does not exclude a PCN.

Genetic findings 
• Approximately 40%–50% of patients with MM have recurrent IGH translocations, while up to 55% lack IGH translocations and are characterized by hyperdiploidy. 
• Approximately 16% (53/336) of MM cases in one cited cohort had FISH findings compatible with t(11;14)(q13;q32)/IGH::CCND1. 
• Molecular findings can support diagnosis but may also occur in other B-cell lymphomas, requiring integrated interpretation.

Reactive plasmacytosis 
• Increased plasma cells in bone marrow alone are not diagnostic of MM; reactive plasmacytosis may exceed 20%. 
• Reactive PCs generally express CD19 and CD138, lack CD56, CD117, and cyclin D1, and show polytypic light-chain expression.

Strengths and limitations  
• The article provides a review of rare morphological and immunophenotypic PCN variants and uses examples to illustrate diagnostic challenges. 
• The authors explicitly note that some observations are based on isolated case reports, small case series, or small cohorts, including the literature concerning pleomorphic/anaplastic myeloma and some immunophenotypic findings. 
• The review notes that the usefulness of CD117 for differentiating PBM from PBL warrants additional studies.

Why this review matters 
The review concludes that increased plasma cells in the bone marrow, morphology alone, or an individual immunophenotypic finding is generally insufficient to establish a diagnosis of MM or another PCN in diagnostically challenging cases. Correct diagnosis requires detailed morphological assessment, appropriate immunophenotyping, molecular studies including clonality and FISH when indicated, and clinical correlation, particularly when distinguishing PCNs from lymphomas, reactive plasmacytosis, and other malignancies.

Reference: 
Chuang, SS., Chang, CC. Diagnostic challenges posed by the wide morphological and immunophenotypic spectrum of plasma cell neoplasms. Blood Res. 61, 61 (2026). https://doi.org/10.1007/s44313-026-00179-6

Bone Marrow Adipocytes in Multiple Myeloma: Emerging Immunometabolic Interactions and Implications for Immunotherapy — Cancers (October 2026)

What is the purpose of the review? 
To examine the role of bone marrow adipocytes (BMAds) in the multiple myeloma (MM) bone marrow microenvironment and their potential effects on myeloma cells, immune-cell function, and responses to immunotherapies. It also identifies potential BMAd-associated pathways for therapeutic intervention and areas requiring further validation.

Summary 
The narrative review summarizes evidence that BMAds are metabolically active components of the MM marrow niche and that myeloma exposure can induce lipid depletion and inflammatory and senescence-associated changes in BMAds. Available evidence links BM lipid exposure to impaired CD8+ T-cell metabolic fitness and leptin receptor activation to reduced invariant natural killer T-cell (iNKT) anti-myeloma activity, while evidence involving conventional NK cells and other immune compartments remains limited. Clinical evidence is predominantly cross-sectional and does not establish that BMAds directly cause resistance to monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), chimeric antigen receptor (CAR) T-cell therapy, or CAR-NK therapy.

Key points 
• BMAd biology: BMAds are metabolically active cells that participate in the myeloma marrow niche through lipid availability, adipokine signaling, inflammatory remodeling, and effects on MM-cell survival.

• Immune effects: BM lipid exposure has been associated with impaired CD8+ T-cell metabolic fitness. Leptin receptor signaling suppresses iNKT anti-myeloma activity in preclinical models, while evidence concerning conventional NK cells remains limited.

• Immunotherapy: The review discusses potential relevance of BMAds to mAbs, antibody-drug conjugates (ADCs), BsAbs, CAR T cells, and CAR-NK cells, but available evidence does not establish that BMAds directly cause resistance to these therapies.

• Potential therapeutic pathways: Candidate areas include lipid handling involving FATP1/4 and FABP4/5, leptin signaling, BMAd senescence, adipsin signaling, parathyroid hormone-induced lipolysis, PPARα-dependent regulation, and statin-sensitive adipogenic remodeling.

• Preclinical findings: Leptin receptor blockade restored iNKT anti-myeloma activity in preclinical models, while senolytic treatment of experimentally senescent adipocytes reduced their protection of MM cells from dexamethasone. The effect of these approaches on immune-mediated anti-myeloma activity remains unestablished.

• Clinical studies: The NUTRIVENTION trial found that greater BMI loss during a high-fiber, plant-based dietary intervention was associated with a trend toward reduced BMAd size in participants with MGUS or SMM and elevated BMI, but it did not establish effects on immune function. The BEAM-MM trial (NCT07564219) is evaluating a ketogenic diet or ketone monoester supplementation in patients receiving BCMA-directed CAR T-cell or BsAb therapy; BMAT and BMAds are not study endpoints.

• Current evidence gap: No clinical study has directly tested whether modifying BMAds changes immunotherapy response in MM.

• Future research: The review recommends patient-derived multicellular models and spatial, longitudinal clinical studies incorporating BMAd/BMAT characteristics, immune states, metabolic features, tumor-cell killing, immune synapse formation, effector-cell persistence, and treatment response.

Strengths 
The review integrates evidence across BMAd biology, immune-cell function, and multiple immunotherapy modalities and identifies specific experimental and clinical validation priorities.

Limitations 
As a narrative review, it does not provide a systematic or quantitative synthesis, and selection bias cannot be excluded. The evidence is heterogeneous and includes primary human BMAds, experimental adipocyte models, non-MM systems, and preliminary conference data; direct studies connecting BMAds with immunotherapy activity are scarce, and several proposed BMAd–immune interactions require functional validation.

Why this review matters 
BMAds are active components of the MM marrow niche, and available evidence indicates that myeloma exposure can alter their metabolic and inflammatory characteristics, with potential effects on tumor and immune-cell function. However, current evidence does not establish that BMAds are clinically relevant causes of immunotherapy resistance or antigen sinks/bystander targets, and their effect on the efficacy of current MM immunotherapies remains unclear. Further spatial, longitudinal, and functional studies are required before BMAd-directed interventions can be evaluated clinically in combination with immunotherapies.

Reference: 
Roque, A., Paiva, A., Seiça, R., & Geraldes, C. (2026). Bone Marrow Adipocytes in Multiple Myeloma: Emerging Immunometabolic Interactions and Implications for Immunotherapy. Cancers, 18(19), 3213. https://doi.org/10.3390/cancers18193213

BCMA-Targeted Immunotherapy in Early Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Practical Management — European Journal of Haematology  (October 2026)

What is the purpose of the review? 
To provide a comparative review of pivotal Phase II and III clinical trials evaluating BCMA-directed therapies for relapsed/refractory multiple myeloma (R/R MM). It compares antibody-drug conjugates (ADCs), bispecific antibodies (BsAbs), and BCMA-directed chimeric antigen receptor T-cell (CAR-T) products with respect to efficacy, durability, toxicity, and treatment sequencing.

Summary 
BCMA-directed therapies showed substantial clinical benefit in early relapse settings, with results including a median PFS of 36.6 months and MRD-negativity of 24.7% for belantamab mafodotin plus bortezomib-dexamethasone (BVd) in DREAMM-7, a median PFS of 32.6 months for belantamab mafodotin plus pomalidomide-dexamethasone (BPd) in DREAMM-8, a 36-month PFS rate of 83.4% for teclistamab plus daratumumab in MajesTEC-3, and a median PFS not reached with ciltacabtagene autoleucel (cilta-cel) versus 11.8 months with standard of care in CARTITUDE-4, with MRD-negativity of 60.6% for cilta-cel. The review also reports that prior BCMA-directed BsAb exposure substantially compromises subsequent CAR-T efficacy, whereas BsAbs retain meaningful activity after prior BCMA-directed CAR-T, and identifies class-specific toxicities including CRS, ICANS, IEC-HS, IEC-EC, and ICAHT.

Key points 
• Therapies reviewed: BCMA-directed ADCs, BsAbs, and CAR-T products in pivotal Phase II and III trials. 
• DREAMM-7: Belantamab mafodotin plus bortezomib-dexamethasone (BVd) had a median PFS of 36.6 months and MRD-negativity of 24.7%. 
• DREAMM-8: Belantamab mafodotin plus pomalidomide-dexamethasone (BPd) had a median PFS of 32.6 months; the abstract states that MRD-negativity data were pending. 
• MajesTEC-3: Teclistamab plus daratumumab had an 83.4% 36-month PFS rate, compared with 29.7% for daratumumab-based triplets. 
• CARTITUDE-4: Cilta-cel had a median PFS that was not reached, compared with 11.8 months with standard of care; MRD-negativity was 60.6%. 
• Treatment sequencing: The review reports that prior BCMA-directed BsAb exposure substantially compromises CAR-T efficacy, while BsAbs retain meaningful activity after prior BCMA-directed CAR-T. 
• Toxicities requiring management: The review specifically identifies cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), IEC-HS, IEC-EC, and ICAHT, as well as belantamab mafodotin-associated ophthalmologic monitoring and dose-adjustment requirements. 
• Limitation: The review notes that efficacy and durability data for some emerging approaches remain comparatively immature relative to autologous CAR-T, and that some approaches are not yet part of standard practice.

Why this review matters 
BCMA-directed ADCs, BsAbs, and CAR-T therapies have demonstrated improved outcomes compared with conventional salvage therapy in early relapsed/refractory multiple myeloma, although the depth and durability of responses differ across platforms. The review identifies treatment sequencing, management of platform-specific toxicities, and multidisciplinary care as important considerations, with available sequencing evidence favoring CAR-T before BCMA-directed BsAb exposure where feasible. Future areas identified by the study include frontline use of BCMA therapies, next-generation and in vivo/allogeneic CAR-T approaches, dual-targeting and combination strategies, and use of MRD negativity as a treatment endpoint.

Reference: 
M. Martino, E. Bilardi, M. Pitea, et al., “BCMA-Targeted Immunotherapy in Early Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Practical Management,” European Journal of Haematology (2026): 1–16, https://doi.org/10.1111/ejh.70328.

Research

The Prognostic Significance of Dynamic Monitoring of Minimal Residual Disease Status in Patients with Multiple Myeloma: A Real-World Study — Cancers (September 2026)

What is the purpose of the study? 
To evaluate whether changes in minimal residual disease (MRD) status before and after autologous stem cell transplantation (ASCT) provide prognostic information beyond a single MRD assessment in patients with newly diagnosed multiple myeloma (MM). It specifically examines longitudinal MRD patterns, the timing of MRD conversion, and quantitative changes in MRD burden in relation to overall survival (OS) and progression-free survival (PFS).

Summary 
This retrospective study analyzed 335 newly diagnosed MM patients who underwent upfront ASCT between 2010 and 2025, with a median follow-up of 127 months. Patients were classified as having persistent MRD negativity (n=82; 24.5%), MRD− to MRD+ conversion (n=40; 11.9%), MRD+ to MRD− conversion (n=168; 50.1%), or persistent MRD positivity (n=45; 13.4%). Persistent MRD negativity was associated with the most favorable survival, while persistent MRD positivity and MRD− to MRD+ conversion were associated with poorer OS and PFS; among patients converting from MRD+ to MRD−, earlier conversion was associated with longer PFS.

Key points

• Study population: 335 patients with newly diagnosed MM who underwent upfront ASCT; patients were treated over a 15-year period, with a median follow-up of 127 months.

• MRD patterns: 
 - Persistent MRD negativity: 82 (24.5%) 
 - MRD− to MRD+ conversion: 40 (11.9%) 
 - MRD+ to MRD− conversion: 168 (50.1%) 
 - Persistent MRD positivity: 45 (13.4%)

• Survival: Persistent MRD negativity was associated with the most favorable outcomes. Median OS was not reached for persistent MRD negativity, compared with 105 months for MRD− to MRD+ conversion, 131 months for MRD+ to MRD− conversion, and 87 months for persistent MRD positivity (p<0.001). Median PFS was not reached, 50 months, 71 months, and 38 months, respectively (p<0.001).

• Multivariable analysis: Compared with persistent MRD negativity, persistent MRD positivity was associated with higher mortality risk (HR 4.762; 95% CI 2.151–10.546; p<0.001) and MRD− to MRD+ conversion was also associated with higher mortality risk (HR 3.925; 95% CI 1.791–8.598; p<0.001). MRD+ to MRD− conversion showed a borderline-significant association (HR 1.973; 95% CI 0.963–4.046; p=0.063).

• Timing of MRD clearance: Among patients who converted from MRD+ to MRD−, late conversion was associated with inferior PFS compared with earlier conversion (HR 1.857; 95% CI 1.136–3.034; p=0.014).

• MRD reappearance: The timing of MRD− to MRD+ conversion was not significantly associated with differences in OS or PFS in subgroup analyses (all p>0.05).

• Quantitative MRD pattern: Among patients with persistent MRD positivity, a stable or increasing MRD burden was associated with worse outcomes (HR 4.397; 95% CI 1.190–16.240; p=0.026).

• MRD assessment: MRD was measured using conventional multiparameter flow cytometry, rather than next-generation flow (NGF) or next-generation sequencing (NGS).

Strengths  
The study was strengthened by prolonged follow-up, comprehensive serial MRD integration, and multivariable adjustment.

Limitations  
• The 15-year inclusion period involved changes in treatment regimens, supportive care, transplant practice, and MRD technologies, with potential residual confounding. 
• Only a small proportion received anti-CD38 monoclonal antibodies, preventing reliable subgroup analysis. 
• Potential measurement variability related to reagent lots, instrument performance, and assay implementation could not be completely excluded. 
• MRD was assessed with conventional multiparameter flow cytometry rather than NGF or NGS, which can achieve sensitivities approaching 10⁻⁶. 
• The retrospective observational design leaves unavoidable confounding. 
• Immortal time bias could not be completely excluded. 
• The 3-month cutoff for early versus late conversion was considered somewhat arbitrary, and MRD assessment intervals were not completely uniform. 
• Some patients had missing MRD data and were excluded, so selection bias could not be completely excluded. 
• Some subgroup analyses had small sample sizes and few outcome events, resulting in wide confidence intervals and reduced statistical power; multiple comparisons could increase the risk of Type I error and false-positive findings. 
• The authors therefore characterized subgroup analyses as exploratory and stated that the survival differences should be interpreted as prognostic associations rather than causal effects.

Why this study matters 
In this cohort of patients with MM undergoing upfront ASCT, longitudinal MRD trajectories provided independent and incremental prognostic information beyond static MRD assessment. Persistent MRD negativity was associated with the most favorable outcomes, while persistent MRD positivity and MRD− to MRD+ conversion were associated with the poorest outcomes; among patients achieving MRD negativity after being MRD-positive, earlier conversion was associated with better PFS. The authors concluded that longitudinal MRD assessment may help refine prognostic risk stratification after ASCT, while noting that the findings require validation in prospective studies.

Reference: 
Zhang, X., Li, X., Liu, J., Huang, B., Gu, J., Chen, M., Kuang, L., & Li, J. (2026). The Prognostic Significance of Dynamic Monitoring of Minimal Residual Disease Status in Patients with Multiple Myeloma: A Real-World Study. Cancers, 18(18), 2958. https://doi.org/10.3390/cancers18182958

The relationship between inflammation and multiple myeloma: insights into alterations and prognostic value — GeroScience (September 2026)

What is the purpose of the study? 
To characterize inflammatory cytokines and the neuropeptide PACAP-38 in patients with multiple myeloma (MM), including those with extramedullary disease (EMD), and to examine their associations with disease activity, EMD, and progression-free survival (PFS). It specifically focuses on the potential prognostic relevance of these biomarkers.

Summary 
Plasma concentrations of 13 cytokines and PACAP-38 were measured using ELISA and Luminex assays in 48 patients with MM and 10 healthy controls. Compared with controls, MM patients had higher IFN-γ, IL-10, and MCP-1 and lower IL-17A and TGF-α; active disease was associated with higher IL-10 and TNF-α, while EMD was associated with higher IFN-γ, IL-10, MCP-1, and PACAP-38 and lower TGF-α. IL-6, IL-10, IL-9, IL-17A, and TGF-α were associated with PFS, and PACAP-38 correlated positively with IL-10 and negatively with MCP-1 and MIP-1α.

Key points 
• Study population: 48 patients with MM and 10 healthy controls. 
• Biomarkers measured: IFN-γ, IL-1β, IL-2, IL-3, IL-6, IL-8, IL-9, IL-10, IL-17A, MCP-1, MIP-1α, TGF-α, TNF-α, and PACAP-38. 
• MM vs healthy controls: MM patients had increased IFN-γ, IL-10, and MCP-1 and decreased IL-17A and TGF-α. 
• Active disease vs remission: IL-10 and TNF-α were markedly higher in the active-disease subgroup. 
• EMD: Patients with EMD had significantly higher IFN-γ, IL-10, MCP-1, and PACAP-38 and markedly lower TGF-α. 
• PFS associations: IL-6, IL-10, IL-9, IL-17A, and TGF-α were associated with PFS in exploratory analyses. 
• PACAP-38 correlations: PACAP-38 correlated positively with IL-10 and negatively with MCP-1 and MIP-1α. 
• Causality: The study was not designed to establish causal relationships or the molecular mechanisms underlying PACAP-38 regulation in EMD.

Strengths 
• Simultaneous assessment of PACAP-38 and a broad panel of inflammatory cytokines. 
• Comprehensive characterization of patients with EMD. 
• Identification of biomarkers associated with disease activity and prognosis.

Limitations  
• Single-center design and relatively small sample size, particularly in the control group and EMD subgroup. 
• Clinically heterogeneous population regarding disease stage, treatment status, and comorbidities, with residual treatment-related confounding unable to be excluded. 
• EMD was biologically heterogeneous but analyzed as a single entity. 
• Peripheral blood rather than bone marrow samples were used, which may not fully represent the bone marrow cytokine environment. 
• IL-1β, IL-2, and IL-3 were below the detection limit in some samples. 
• Cross-sectional design prevented assessment of temporal cytokine changes and causal inference. 
• The small sample size and low number of progression events prevented robust multivariable Cox regression and determination of independent prognostic value beyond established clinical risk factors. 
• Several nominally significant associations were no longer statistically significant after correction for multiple testing. 
• Larger, independent, multicenter studies with longitudinal follow-up are required for validation.

Why this study matters 
The study found distinct inflammatory and PACAP-38 profiles in MM, active disease, and EMD, with several biomarkers associated with disease activity or PFS. However, the findings are exploratory, and the study did not establish causal relationships or the independent prognostic value of these biomarkers; larger, independent, longitudinal studies are needed to validate their clinical utility.

Reference:  
Tóth, T., Alizadeh, H., Polgár, B. et al. The relationship between inflammation and multiple myeloma: insights into alterations and prognostic value. GeroScience (2026). https://doi.org/10.1007/s11357-026-02494-3

PKMYT1 is a targetable vulnerability in del(17p) high-risk multiple myeloma — Blood (September 2026)

What is the purpose of the study? 
To identify therapeutic vulnerabilities associated with deletion of chromosome 17p [del(17p)] in multiple myeloma (MM), a high-risk cytogenetic abnormality. It specifically evaluated protein kinase membrane-associated tyrosine/threonine 1 (PKMYT1) as a potential therapeutic target in del(17p) and/or TP53-altered MM.

Summary 
Using RNA sequencing data from patients with MM and genetic dependency data from MM cell lines, researchers identified PKMYT1 as a potential vulnerability in del(17p) MM. Genetic suppression or pharmacological inhibition with the selective PKMYT1 inhibitor RP-6306 caused DNA damage, micronucleus formation, premature mitotic entry, and mitotic catastrophe, resulting in preferential cell death in del(17p) MM cells while largely sparing del(17p)-negative MM and healthy cells. In xenograft and TP53-deficient syngeneic models, RP-6306 reduced tumor burden and extended survival.

Key points 
• PKMYT1 vulnerability: PKMYT1, a regulator of the G2/M cell-cycle checkpoint, was identified as a potential vulnerability in MM cells with del(17p) and/or TP53 mutations. 
• Mechanism observed: PKMYT1 inhibition activated CDK1 and promoted premature mitotic entry, with accumulation of DNA damage, micronuclei, and mitotic catastrophe, leading to cell death. 
• Selectivity observed: RP-6306 preferentially affected del(17p) MM cells, while largely sparing del(17p)-negative MM cells and healthy cells in the reported experiments. 
• In vivo findings: RP-6306 reduced tumor burden and extended survival in both xenograft and TP53-deficient syngeneic models. 
• Combination findings: PKMYT1 inhibition showed synergistic activity with DNA-damaging agents in the reported experiments.

Limitations 
• The models lacked matched genomic annotations, preventing assessment of whether alterations such as FBXW7 or PPP2R1A contributed to RP-6306 sensitivity in TP53-altered cells. 
• Further studies using genomically annotated cohorts and/or isogenic models were identified as necessary to determine whether sensitivity is driven by TP53 alterations alone or together with additional genetic features. 
• Partial rescue by the CDK1 inhibitor RO-3306 indicated that other kinases may contribute to the observed phenotype; these contributors remain to be defined. 
• Further studies were identified as necessary to understand the effects of RP-6306 on immune responses in the MM tumor microenvironment and its potential interaction with immunotherapy.

Why this study matters 
The study identified PKMYT1 as a vulnerability in MM cells with del(17p) and/or TP53 dysfunction and found that RP-6306 induced DNA damage and mitotic catastrophe, with preferential cell death in del(17p) MM models. RP-6306 also reduced tumor burden and extended survival in the reported animal models, while the authors identified additional studies needed to clarify determinants of sensitivity and underlying mechanisms.

Reference: 
Anaïs Schavgoulidze, Jian Cui, Jessica Encinas Mayoral, Vanessa Favasuli, Srikanth Talluri, Sabrina Maheo, Chloé Cerutti, Masood Shammas, Daniel Primo, Carmen Vicente, Marta Larrayoz, José A. Martínez-Climent, Kenneth C. Anderson, Anil Aktas-Samur, Mehmet Kemal Samur, Hervé Avet-Loiseau, Jill Corre, Nikhil C. Munshi, Mariateresa Fulciniti; PKMYT1 is a targetable vulnerability in del(17p) high-risk multiple myeloma. Blood 2026; 148 (12): 1559–1571. doi: https://doi.org/10.1182/blood.2026033819

Incidentally detected vertebral fractures and risk of myeloma: a prospective cohort study of 9059 CT-scanned Danish general population individuals — Leukemia (September 2026)

What is the purpose of the study? 
To investigate the risk of myeloma and non-hematologic cancers among individuals with incidentally detected vertebral fractures on CT scans. It aims to address uncertainty about whether these individuals should routinely undergo evaluation for underlying malignancy.

Summary 
This study included 9,059 Danish adults aged 40–94 years from the Copenhagen General Population Study who underwent low-dose CT scanning; vertebral compression fractures were assessed at Th10–Th12 and L1–L5, and subsequent diagnoses were identified through nationwide Danish health registries. Individuals with incidentally detected vertebral fractures had an increased relative risk of myeloma, but the absolute 5-year risk was quite modest, including among those with the most severe fractures, while no increased risk of non-hematologic cancer was observed.

Key points 
• Population: 9,059 CT-scanned individuals aged 40–94 years from the Danish general population. 
• Exposure: Incidentally detected vertebral compression fractures in Th10–Th12 and L1–L5, graded using the Genant semiquantitative method. 
• Myeloma: Vertebral fractures were associated with an increased relative risk of myeloma, but the absolute 5-year risk was quite modest. 
• Non-hematologic cancer: Individuals with vertebral fractures were not at increased risk of any non-hematologic cancer.

Strengths 
• Nationwide Danish registries provided information on myeloma diagnoses without losses to follow-up. 
• The general population design enrolled participants based on age and geography rather than symptoms or previous hospital visits.

Limitations  
• Limited statistical power for subgroup analyses. 
• CT scans covered only the lumbar and lower thoracic vertebrae. 
• Participants were predominantly white and of Danish descent, so results might not be representative of other populations. 
• Risk estimates may not be generalizable to individuals CT-scanned because of symptoms or clinical suspicion of myeloma.

Why this study matters 
In this Danish general population study, incidentally detected vertebral fractures were associated with an increased relative risk of myeloma, but the absolute 5-year risk remained quite modest. No increased risk of non-hematologic cancer was observed, and the authors concluded that evaluation for underlying myeloma is likely of limited or no benefit unless symptoms or other clinical findings raise suspicion of myeloma.

Reference: 
Rønnemoes, R., Juhl, A.R., Afzal, S. et al. Incidentally detected vertebral fractures and risk of myeloma: a prospective cohort study of 9059 CT-scanned Danish general population individuals. Leukemia (2026). https://doi.org/10.1038/s41375-026-03135-6

Germline Genomic and DNA Methylation Differences Between MGUS and Multiple Myeloma Among Patients of African Ancestry — Cells (September 2026)

What is the purpose of the study? 
To identify germline genetic and DNA methylation features associated with multiple myeloma (MM) compared with monoclonal gammopathy of undetermined significance (MGUS) among individuals of African ancestry (AA). It also evaluates epigenetic age, DNA methylation–estimated telomere length (DNAmTL), and biological pathways potentially associated with MM status.

Summary 
Researchers performed whole-exome sequencing (WES) and genome-wide DNA methylation profiling in 28 AA patients with MM and 28 frequency-matched AA patients with MGUS without documented progression; after quality control, analyses included 27 MM and 28 MGUS patients for WES and 26 MM and 27 MGUS patients for methylation. Qualifying COL19A1 variants were observed only in MGUS and qualifying VWA5B2 variants only in MM, while exploratory gene-burden signals in LAMA5 and PIEZO1 did not remain significant after Bonferroni correction; methylation analysis identified 703 differentially methylated positions, 122 exploratory candidate differentially methylated regions, and one RNF39 region spanning 16 CpG sites that met the family-wise error rate threshold. Epigenetic age acceleration did not differ significantly between groups, whereas age-adjusted DNAmTL residuals were lower in MM, with the difference becoming borderline after adjustment for DNAm-estimated blood-cell composition.

Key points

Genomic findings 
• Qualifying COL19A1 variants occurred only in the MGUS group, while qualifying VWA5B2 variants occurred only in the MM group within this cohort. 
• LAMA5 and PIEZO1 showed nominal exploratory gene-burden signals, but neither remained significant after Bonferroni correction.

DNA methylation 
• Identified 703 differentially methylated positions and 122 exploratory candidate differentially methylated regions between MM and MGUS. 
• One 395-bp RNF39 region spanning 16 CpG sites met the family-wise error rate significance threshold.

Epigenetic age and telomere length 
• No statistically significant difference in epigenetic age acceleration (EAA) was detected. 
• The study did not provide sufficient evidence that the rate of DNAmTL decline differed between groups. 
• Age-adjusted DNAmTL residuals were lower in MM before additional adjustment; after adjustment for DNAm-estimated blood-cell composition, the difference was −0.123 (95% CI, −0.246 to −0.0001; p = 0.050), and the authors characterized this finding as exploratory. 
• The EAA analysis had limited statistical power; smaller between-group differences could not be excluded.

Strengths  
• MGUS patients without documented progression for at least five years provided a clinically meaningful comparator. 
• MM samples were collected at diagnosis and before systemic treatment. 
• Groups were matched on age and sex, and technical batch effects were addressed using ComBat.

Limitations  
• Modest sample sizes limited statistical power, particularly for rare-variant analyses. 
• No independent validation cohort was available. 
• MGUS classification reflected only the observed follow-up period, and some participants could subsequently develop MM. 
• The cross-sectional design could not establish whether genomic or epigenetic differences preceded or contributed causally to MM. 
• DNA methylation may have been influenced by established disease, inflammation, aging, and circulating blood-cell composition; measured blood-cell composition was unavailable. 
• Pathway analyses were exploratory and potentially sensitive to methodological factors; IPA enrichment p values were not adjusted for multiple testing. 
• Formal multi-omics integration and functional validation were not performed. 
• The single-center cohort may not fully represent genetic and epigenetic heterogeneity within AA populations.

Why this study matters 
The study identified exploratory germline and DNA methylation features associated with MM versus MGUS without documented progression during the observed follow-up period in AA patients. The authors state that larger independent cohorts, longitudinal studies with appropriate adjustment for blood-cell composition, matched genomic/methylation/gene-expression data, and functional investigations are needed to determine whether these findings are reproducible and related to subsequent MM development.

Reference: 
Han, J., Liu, S. H., Arsang-Jang, S., Xu, Z., Rentscher, K. E., Mathison, A. J., Tschannen, M., Sun, F., Auer, P. L., Kerns, S., Hari, P., Dhakal, B., Janz, S., Jin, V. X., Urrutia, R., D’souza, A., & Dong, J. (2026). Germline Genomic and DNA Methylation Differences Between MGUS and Multiple Myeloma Among Patients of African Ancestry. Cells, 15(19), 1722. https://doi.org/10.3390/cells15191722

Exploring the psychological impact and healthcare experiences of patients living with triple class refractory multiple myeloma: an interpretative phenomenological analysis study — BMJ Open (September 2026)

What is the purpose of the study? 
To explore the psychological impact and healthcare experiences of patients with triple-class refractory multiple myeloma (TCRMM), including their experiences with treatment decisions and clinical trials. It is part of a wider qualitative study examining experiences across different stages of MM treatment exposure.

Summary 
This qualitative study used semi-structured interviews and Interpretative Phenomenological Analysis with seven patients with TCRMM (five men and two women; age 41–84 years) recruited through Myeloma UK. Three themes were identified: matching psychological support to specific moments, finding a voice in treatment decisions, and learning to navigate clinical trials, reflecting reported needs for psychological support, greater involvement in shared decision-making (SDM), and clearer information and access pathways for clinical trials (CTs).

Key points 
• Participants: 7 patients with TCRMM; 5 men and 2 women; age 41–84 years. 
• Three overarching themes: 
 - Psychological support: Patients described psychological burden related to MM, its treatments, diagnosis, relapse, uncertainty, and side-effects, and identified specific timepoints when psychological input was needed. 
 - Treatment decisions: Patients reported wanting greater involvement in treatment decisions, with their preferences and priorities recognised and SDM incorporated into consultations. 
 - Clinical trials: Patients described difficulties obtaining transparent information about CTs and navigating complex eligibility and exclusion criteria.

• Patients reported that relationships with healthcare professionals (HCPs), communication, and involvement in SDM were important aspects of their treatment experiences.

• The clinical implications identified by the authors included increased psychological services, practical tools supporting psychological well-being and SDM, patient-focused educational materials, further HCP communication training, and improved access to CT information.

Strengths  
• Interpretative phenomenological analysis enabled detailed exploration of patients’ lived experiences. 
• Patient and public involvement through a Service User Advisory Group enhanced methodological validity and reduced researcher bias. 
• The study provided an in-depth examination of the TCRMM journey from the patient perspective.

Limitations  
• All participants were white British, which may limit generalizability to ethnic minority groups. 
• The study was qualitative; the authors stated that a future quantitative study could support statistical generalisation of the identified challenges. 
• The study focused on patient perspectives and did not primarily examine HCP perspectives.

Why this study matters 
The study identified substantial psychological and healthcare-related challenges reported by patients with TCRMM, particularly concerning psychological support, participation in treatment decisions, and navigating clinical trials. The authors concluded that patients should have more routinely available psychological support, practical resources for informed decision-making, and accessible information about treatments and clinical trials.

Reference: 
Ali N, Kuttschreuter L, Quinn S, et al. Exploring the psychological impact and healthcare experiences of patients living with triple class refractory multiple myeloma: an interpretative phenomenological analysis study, BMJ Open 2026;16:e108269. doi: 10.1136/bmjopen-2025-108269

Spatial transcriptomics identifies a suppressive, T-cell–excluded tumor microenvironment in extramedullary myeloma — Blood Advances (September 2026)

What is the purpose of the study? 
To characterize the spatial organization and tumor microenvironment (TME) of extramedullary disease (EMD) in multiple myeloma (MM). It specifically examines immune-cell composition, recurrent TME niches, and predicted interactions between plasma cells (PCs) and TME cells.

Summary 
Using spatial transcriptomics of EMD tumor biopsies, the researchers observed substantial interpatient variability in PC gene-expression profiles while the PCs retained a characteristic PC transcriptome. The observed TME was dominated by suppressive “M2” macrophages, and CD8+ T cells frequently expressed the exhaustion markers LAG3 and TIGIT; three recurrent TME niches were identified based on immune-cell composition: immune excluded (IE), immune suppressed (IS), and immune permissive (IP). Cell-cell interaction modeling using CellPhoneDB predicted reciprocal interactions in which PCs modulated the TME through PGE2 and VEGFB, while interactions involving TME cells were predicted to provide canonical MM prosurvival signals involving CD38, CXCR4, and BCMA and to promote a suppressive macrophage phenotype and fibrotic extracellular matrix (ECM).

Key points 
• TME composition: The observed TME was dominated by suppressive “M2” macrophages. CD8+ T cells frequently expressed LAG3 and TIGIT. 
• Recurrent niches: Three recurrent TME niches were identified: immune excluded (IE), immune suppressed (IS), and immune permissive (IP). 
• Immune exclusion: The IE niche comprised the bulk of tumors and was characterized by extensive malignant PC involvement with very few immune cells. 
• Immune-suppressed niche: The IS niche contained suppressive macrophages together with endothelial cells, cancer-associated fibroblasts, and cytotoxic T cells. 
• Immune-permissive niche: The IP niche contained the highest proportion of infiltrating T cells and the most inflammatory macrophages, although these macrophages still expressed suppressive markers. 
• Predicted cell-cell interactions: CellPhoneDB modeling predicted reciprocal interactions between PCs and TME cells. PC/macrophage and PC/fibroblast interactions were predicted to support PC growth and survival through canonical MM survival pathways involving CD38 and BCMA, with APRIL and BAFF also implicated. 
• Predicted immunosuppressive effects: PC/macrophage interactions were predicted to promote an “M2” macrophage phenotype, while fibroblast interactions were predicted to contribute to suppressive macrophage characteristics and ECM formation that may contribute to T-cell exclusion and dysfunction. 
• T-cell function: The expression of LAG3 and TIGIT was consistent with a suppressive TME, but the authors explicitly state that T-cell activity in EMD cannot be confirmed without further experimental validation.

Limitations 
The study had a relatively small sample size; broad gene assessment resulted in lower coverage depth than targeted approaches; Xenium spatial transcriptomics is not truly quantitative like sequencing-based techniques; and some relevant genes, including SDF1 (CD138), were unavailable for assessment, potentially underestimating some cell-cell interactions.

Why this study matters 
The study described recurrent immune microenvironments in EMD, with the observed TME characterized by suppressive macrophages, fibroblasts, and extensive T-cell exclusion from much of the tumor. Computational cell-cell interaction modeling predicted reciprocal interactions between PCs and TME cells that may support PC survival and promote an immunosuppressive environment, providing a rationale for further investigation of strategies targeting tumor burden and specific TME interactions.

Reference:  
Nicholas E. Bingham, Julie R. Boiko, Daniel C. Jones, Daniel Wong, Tiffany Khong, Sridurga Mithraprabhu, Kathleen S. Ensbey, Anna E. Elz, Evan W. Newell, Andrew Spencer, Geoffrey R. Hill; Spatial transcriptomics identifies a suppressive, T-cell–excluded tumor microenvironment in extramedullary myeloma. Blood Adv 2026; 10 (18): 6221–6235. doi: https://doi.org/10.1182/bloodadvances.2026020500

Evolution of real-world frontline treatment patterns in multiple myeloma — Blood Advances (September 2026)

What is the purpose of the study? 
To evaluate changes in overall survival (OS), treatment patterns, and sociodemographic factors among patients with newly diagnosed multiple myeloma (NDMM) treated in the nationwide Veterans Affairs (VA) health care system from 2000 through 2024. It specifically examines whether socioeconomic disadvantage was associated with survival despite access to VA health care.

Summary 
Researchers retrospectively analyzed 20,135 patients with NDMM who received initial MM treatment in the VA system between 2000 and 2024, comparing OS across treatment eras, treatment regimens, and sociodemographic characteristics. OS improved across successive treatment eras, while higher area deprivation index (ADI), a measure of neighborhood socioeconomic disadvantage, was independently associated with increased mortality despite the VA's equal-access health care setting. The study also found no statistically significant OS difference between quadruplet regimens (IMiD + MA + PI) and triplet regimens (IMiD + PI), although the quadruplet group was small and had limited follow-up.

Key points 
• Population: 20,135 patients with NDMM treated in the nationwide VA health care system from 2000–2024. 
• Primary outcome: Overall survival, measured from the start of MM treatment. 
• Treatment trends: OS improved across successive diagnosis/treatment eras as newer MM therapies were adopted. 
• Socioeconomic disadvantage: Increasing ADI was associated stepwise with increased mortality after adjustment for other measured factors. 
• Treatment regimens: Modern combined regimens, including triplet and quadruplet therapies, were associated with the broader improvement in survival over time. 
• Quadruplet vs triplet therapy: No statistically significant OS difference was observed between IMiD + MA + PI and IMiD + PI regimens in this analysis. 
• Race and ethnicity: Black patients had improved OS compared with White patients, and Hispanic or Latino patients had improved OS compared with non-Hispanic or Latino patients. 
• BMI: Higher BMI was associated with improved OS in this analysis.

Limitations 
• The VA population was overwhelmingly male. 
• Heterogeneous treatment regimens had to be grouped into broader categories, particularly within the “other” category. 
• ISS and R-ISS data were combined according to availability. 
• Maintenance therapy and cytogenetic data could not be effectively extracted, creating potential residual confounding. 
• The retrospective, observational design limits causal inference, and prospective studies are needed to validate the findings. 
• The most recent treatment cohort had limited follow-up, particularly for quadruplet therapy.

Why this study matters 
In this national VA cohort of patients with NDMM, OS improved across treatment eras, while socioeconomic disadvantage remained independently associated with worse survival despite access to VA health care. The study reports that social and structural factors remained associated with outcomes, and that longer follow-up and prospective studies are needed, particularly to characterize outcomes with recently introduced treatment regimens.

Reference: 
Alexander Lazzaro, Kaelyn Nannini, Cenk Yildirim, Linden Huhmann, John M. Culnan, June K. Corrigan, Danne Elbers, Nhan V. Do, Mary Brophy, Nikhil Munshi, Nathanael R. Fillmore, Camille V. Edwards; Evolution of real-world frontline treatment patterns in multiple myeloma. Blood Adv 2026; 10 (18): 6278–6288. doi: https://doi.org/10.1182/bloodadvances.2026019843

Dynamic risk stratification in smoldering multiple myeloma: Integrating evolving biomarkers with the 2/20/20 Model — HemaSphere (September 2026)

What is the purpose of the study? 
To determine whether evolving M-protein (eMP) and evolving free light chain ratio (eFLCr) during the first year after diagnosis could improve prediction of progression from smoldering multiple myeloma (SMM) to multiple myeloma (MM) when incorporated into the 2/20/20 risk model.

Summary 
This retrospective longitudinal study included 323 patients with SMM diagnosed according to IMWG 2014 criteria at Memorial Sloan Kettering Cancer Center from 2002–2019. An increase in M-protein ≥0.4 g/dL (eMP) or FLCr ≥40% (eFLCr) during the first year was independently associated with progression to MM, with hazard ratios of 2.8 (95% CI, 1.5–5.5) and 2.9 (95% CI, 1.8–4.8), respectively. Incorporating these evolving biomarkers into the 2/20/20 model increased the C-index from 0.70 to 0.79; patients with high baseline risk plus evolving markers had 2- and 5-year progression rates of 41% and 83%, respectively, whereas low-risk patients without evolving disease had a 5-year progression rate of 8%.

Key points 
• Population: 323 patients with SMM diagnosed using IMWG 2014 criteria and followed at a single academic institution. 
• Evolving biomarkers: 
 - eMP: M-protein increase ≥0.4 g/dL within 12 months. 
 - eFLCr: FLCr increase ≥40% within 12 months.

• Independent predictors of progression: 
 - eMP: HR 2.8 (95% CI, 1.5–5.5). 
 - eFLCr: HR 2.9 (95% CI, 1.8–4.8).

• Median time to progression: 18 months with eMP vs 130 months without eMP; 41 months with eFLCr vs 201 months without eFLCr. 
• Risk-model performance: Incorporating evolving biomarkers into the 2/20/20 model increased the C-index from 0.70 to 0.79. 
• High baseline risk with eMP and/or eFLCr: 2- and 5-year progression rates were 41% and 83%, respectively. 
• High baseline risk without evolving markers: 2- and 5-year progression rates were 10% and 45%, respectively. 
• Low baseline risk without evolving disease: 5-year progression rate was 8%, with a disease course described by the authors as resembling MGUS.

Strengths
• Large, well-defined SMM cohort
• Longitudinal markers
• Long-term clinical follow-up

Limitations
• Retrospective design
• Inclusion of patients from a single academic institution with potential selection bias
• Inability of the dynamic model to identify patients who progress within the first 12 months
• The need for external validation in an independent population

Why this study matters 
Evolving M-protein (eMP ≥0.4 g/dL) and evolving FLC ratio (eFLCr ≥40%) within the first year after SMM diagnosis were independent predictors of progression to active MM. Incorporating these evolving biomarkers into the 2/20/20 model improved predictive performance and provided additional risk stratification, while the authors note that external validation in an independent population is needed to confirm broader applicability.

Reference: 
Akhlaghi, T., Nemirovsky, D., Maclachlan, K.H., Firestone, R.S., Korde, N., Mailankody, S., Lesokhin, A.M., Hassoun, H., Patel, D., Shah, U.A., Tan, C.R., Landau, H.J., Shah, G.L., Scordo, M., Simhal, A.K., Landgren, O., Giralt, S.A., Usmani, S.Z., Derkach, A. and Hultcrantz, M. (2026), Dynamic risk stratification in smoldering multiple myeloma: Integrating evolving biomarkers with the 2/20/20 Model. HemaSphere, 10: e70473. https://doi.org/10.1002/hem3.70473

The Converging Roles of DNA Damage Resolution and Redox Dysregulation in Plasma Cell Transformation During the Evolution of Multiple Myeloma — International Journal of Molecular Sciences (September 2026)

What is the purpose of the study? 
To investigate how DNA damage response (DDR)-related parameters and redox status change during the progression from monoclonal gammopathy of undetermined significance (MGUS) to smoldering multiple myeloma (SMM) and multiple myeloma (MM). It also examines whether combined DDR-related measures could distinguish patients across these disease stages.

Summary 
Bone marrow plasma cells from 16 patients with MGUS, 18 with SMM, and 15 with MM were evaluated for redox status, DNA damage, DNA damage processing, chromatin organization, and apoptotic sensitivity. Across disease stages, endogenous DNA damage and abasic-site burden increased, while the GSH/GSSG ratio, chromatin condensation, and apoptotic sensitivity decreased; UVC-induced DNA damage and melphalan-induced γH2AX signal showed progressively faster resolution. Multivariate analyses identified DDR-associated patterns that partially separated MGUS, SMM, and MM cases.

Key points 
• Study population: 16 MGUS, 18 SMM, and 15 MM patients. 
• DNA damage: Baseline DNA strand breaks, alkali-labile sites, and apurinic/apyrimidinic (AP) sites progressively accumulated across disease stages. 
• Redox status: The GSH/GSSG ratio progressively decreased, indicating a shift toward a more oxidizing intracellular environment. 
• DNA damage resolution: Residual UVC-induced comet-detectable DNA damage and melphalan-induced γH2AX foci declined progressively faster from MGUS to MM. 
• Important methodological limitation: The alkaline comet assay does not directly measure UV photoproduct removal, and γH2AX foci reflect DSB-associated signaling and its resolution rather than directly demonstrating completion of DSB repair.

• Chromatin: Chromatin accessibility at the N-ras locus progressively increased; the study explicitly notes that this single-locus finding cannot be extrapolated to genome-wide chromatin relaxation.

• Apoptosis: Apoptotic sensitivity progressively decreased from MGUS to SMM to MM.

• Clustering: Hierarchical clustering partially separated disease stages; most MGUS samples clustered together, while most MM samples formed a distinct cluster, with SMM distributed between the principal clusters.

Limitations 
The study had a relatively modest sample size, lacked demographic and clinical matching between disease-stage groups, and did not perform formal statistical comparisons, multivariable adjustment, or sensitivity analyses for clinical characteristics.

Why this study matters 
Progression from MGUS through SMM to MM was associated with progressive changes in DNA damage accumulation and processing, DDR-related signaling, chromatin organization, apoptotic sensitivity, and redox status. The study's multivariate analyses identified stage-associated DDR patterns, while the authors note that larger, well-characterized cohorts and pathway-specific assays are needed to determine the contribution of individual mechanisms and potential confounding variables.

Reference: 
Malamos, P., Koutoulogenis, K., Gavriatopoulou, M., Terpos, E., & Souliotis, V. L. (2026). The Converging Roles of DNA Damage Resolution and Redox Dysregulation in Plasma Cell Transformation During the Evolution of Multiple Myeloma. International Journal of Molecular Sciences, 27(19), 8595. https://doi.org/10.3390/ijms27198595

Efficacy and safety of frail patients treated with ciltacabtagene autoleucel in the real world: A Center for International Blood and Marrow Transplant Research analysis — Cancer (September 2026)

What is the purpose of the study? 
To evaluate outcomes and safety of commercial ciltacabtagene autoleucel (cilta-cel) in frail adults with relapsed/refractory multiple myeloma (RRMM) using real-world data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Frailty is assessed using age, ECOG performance status, and comorbidity burden.

Summary 
Among 541 patients who received standard-of-care cilta-cel between March 2022 and December 2023, 183 (33.8%) were classified as frail and 358 (66.2%) as nonfrail. Overall response rates were comparable between frail and nonfrail patients (82.8% vs. 88.5%), and frailty was not independently associated with overall response rate (ORR) or complete response in multivariable analysis. However, 12-month progression-free survival (PFS) was 62.7% versus 75.9% and overall survival (OS) was 72.8% versus 90.4%, respectively; frailty independently predicted shorter PFS (HR 1.67) and OS (HR 2.46). Frail patients also had more any-grade immune effector cell–associated neurotoxicity syndrome (ICANS) (32.2% vs. 17.6%; OR 2.01) and prolonged cytopenia beyond day 30 (30.6% vs. 21.2%).

Key points 
• Population: 541 adults with RRMM receiving standard-of-care cilta-cel after ≥4 prior lines of therapy; 183 (33.8%) were frail. 
• Response: ORR was 82.8% in frail vs. 88.5% in nonfrail patients. Frailty was not independently associated with ORR or complete response in multivariable analysis. 
• PFS: 12-month PFS was 62.7% vs. 75.9% (p < .01); frailty independently predicted shorter PFS (HR 1.67, 95% CI 1.16–2.40). 
• OS: 12-month OS was 72.8% vs. 90.4% (p < .01); frailty independently predicted shorter OS (HR 2.46, 95% CI 1.57–3.87). 
• ICANS: Any-grade ICANS occurred in 32.2% vs. 17.6% (p < .01); frailty was independently associated with ICANS (OR 2.01, 95% CI 1.32–3.08). 
• Other safety findings: Grade ≥2 cytokine release syndrome occurred in 22.4% vs. 17.9% (p = .05), and prolonged cytopenia beyond day 30 occurred in 30.6% vs. 21.2% (p < .01). 
• Treatment-related mortality: At 12 months, treatment-related mortality was 6.8% vs. 3.6% (p = .12).

Strengths 
Large, geographically diverse cohort; standardized, prospectively collected CIBMTR data; and robust modeling that adjusted for disease status at infusion, cytopenias, marrow burden, prior BCMA-directed therapies, and other clinically relevant covariates.

Limitations 
Observational design with potential residual confounding; possible selection of a more fit population because only patients meeting product and study-entry requirements were included; an adapted frailty index that did not capture all geriatric domains; center-level variation in adjudication of delayed neurotoxicity and infection; and modest median follow-up for late events such as second primary malignancies.

Why this study matters 
In this CIBMTR observational cohort, frailty was not independently associated with the likelihood of achieving an initial overall or complete response to cilta-cel, but it was independently associated with shorter PFS and OS. Frail patients also had higher rates of any-grade ICANS and prolonged cytopenia, while the difference in 12-month treatment-related mortality was not statistically significant.

Reference: 
Mian H, Faisal MS, Chen T, et al. Efficacy and safety of frail patients treated with ciltacabtagene autoleucel in the real world: A Center for International Blood and Marrow Transplant Research analysis. Cancer. 2026;e70614. doi:10.1002/cncr.70614

Multiple Myeloma: Insights Into a Challenging Diagnostic Journey — Journal of Primary Care & Community Health (September 2026)

What is the purpose of the study? 
To explore the diagnostic journeys of adults with multiple myeloma (MM), from initial symptom onset to diagnosis, and identify barriers and facilitators to timely diagnostic resolution. It specifically examines experiences during the appraisal, help-seeking, and diagnostic intervals.

Summary 
This qualitative descriptive study interviewed 34 adults diagnosed with MM within the previous 10 years in the United States; participants were 38.2% Black, 35.3% White, 20.6% Hispanic, and 5.9% Asian. Facilitators of timely diagnosis included recognition of health changes, persistent advocacy, and regular primary care engagement, while barriers included symptom misattribution by patients and providers, prolonged conservative management, and limited awareness of MM. Participants commonly reported non-specific symptoms and CRAB features—hypercalcemia, renal insufficiency, anemia, and bone lesions—before diagnosis, which sometimes led to treatment for more common conditions rather than evaluation for MM.

Key points 
• Study design: Qualitative descriptive study using semi-structured interviews and reflexive thematic analysis guided by the Model of Pathways to Treatment (MPT). 
• Participants: 34 adults with MM diagnosed within the previous 10 years; interviews were conducted in English or Spanish. 
• Facilitators of timely diagnosis: 
 - Recognition of health changes by patients or others
 - Persistent patient advocacy
 - Regular engagement with primary care
 - Escalation of care for new, concerning, persistent, or worsening symptoms

• Barriers to timely diagnosis: 
 - Non-specific presenting symptoms
 - Misattribution of symptoms by patients and healthcare providers
 - Prolonged conservative management or treatment for more common conditions
 - Limited awareness of MM among patients and providers
 - Challenges accessing primary care, including provider shortages, healthcare coverage gaps, and healthcare mistrust

• Diagnostic considerations: The study states that when MM is suspected, recommended initial testing includes serum protein electrophoresis with immunofixation (SPEP w/IFE) and serum free light chain assay (sFLC).

• Screening: Routine screening for MM is not currently recommended; the iStopMM (Iceland Screens Treats or Prevents Multiple Myeloma) study is investigating potential benefits and harms of MM screening.

• Emerging approaches: The study discusses educational initiatives and machine learning/artificial intelligence approaches for earlier MM detection but states that further research is needed.

Strengths 
The study included a relatively diverse sample, obtained rich in-depth accounts of diagnostic journeys, used iterative coding and thematic analysis, and incorporated community advisory board input and triangulation.

Limitations 
• Most participants were recruited from a single academic institution in the Southeastern United States, limiting applicability to other regions and care settings. 
• The small sample size limits generalizability. 
• Retrospective accounts may have been affected by memory limitations, reinterpretation in hindsight, and social desirability bias.

Why this study matters 
MM diagnosis was often delayed in participants because of non-specific symptoms, symptom misattribution, and limited awareness among patients and providers. Regular primary care engagement and persistent advocacy were identified as facilitators, while misdirected treatment and systemic access challenges were barriers; the study identifies public education, provider training on MM signs and appropriate testing, and improved primary care access as areas for further intervention and research.

Reference: 
LeBlanc MR, Luna M, Bennington K, et al. Multiple Myeloma: Insights Into a Challenging Diagnostic Journey. Journal of Primary Care & Community Health. 2026;17. doi:10.1177/21501319261492515

Sequencing BCMA-Directed Therapies in Relapsed/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies — Cancers (September 2026)

What is the purpose of the study? 
To evaluate the real-world effectiveness of BCMA-directed therapies (BDT), comparing chimeric antigen receptor T-cell therapy (CAR-T) with bispecific antibodies (BsAbs) in patients with relapsed/refractory multiple myeloma (RRMM). It also examines outcomes according to whether patients had received prior BDT and explored factors associated with treatment outcomes.

Summary 
In this multicenter retrospective cohort, 276 BDT-naïve patients received either CAR-T (169; 61%) or BsAbs (107; 39%): median progression-free survival (PFS) was 16.1 versus 13.5 months (p=0.007), and overall response rate (ORR) was 87% versus 68%, respectively. Among 80 BDT-exposed patients, median PFS was 6.3 months with CAR-T and 4.4 months with BsAbs, with ORRs of 64% and 53%, respectively; responses to both modalities were lower after prior BDT exposure.

Key points 
• BDT-naïve patients: CAR-T was associated with longer median PFS than BsAbs (16.1 vs. 13.5 months; p=0.007) and a higher ORR (87% vs. 68%). 
• BDT-exposed patients: Median PFS was 6.3 months with CAR-T versus 4.4 months with BsAbs; ORR was 64% versus 53%, respectively. 
• Prognostic factors: Achieving a best response of ≥very good partial response (VGPR) was associated with longer PFS and overall survival (OS). High-risk cytogenetic abnormalities (HRCA) were associated with poorer PFS and OS in the BDT-naïve cohort. 
• Safety: CAR-T was associated with more cytopenias, whereas BsAbs were associated with higher infection rates.

Strengths 
The study was described as one of the largest real-world multicenter retrospective cohorts evaluating BDT modalities in both BDT-naïve and BDT-exposed settings.

Limitations  
Retrospective design limits causal inference; treatment groups had baseline differences and residual confounding may remain despite adjustment. Other limitations included missing information on prior BDT duration and outcomes, MRD assessments, response timing, bridging strategies, and supportive care; the BsAb cohort included only teclistamab; the BDT-exposed cohort was relatively small; follow-up differed between cohorts; and institutional practices may have affected infection and cytopenia outcomes.

Why this study matters 
In this real-world multicenter study, CAR-T was associated with longer PFS and higher ORR than BsAbs among BDT-naïve patients, while both treatment modalities showed less durable responses after prior BCMA-directed therapy. The authors concluded that prospective studies are needed to further define treatment selection and sequencing of BDT in RRMM.

Reference: 
Younis, O. M., Goklemez, S., Awadallah, C., Atrash, S., Paul, B., Shaikh, H., Strouse, C., Vegel, A., Struble, E., Mazloom, A., Alkharabsheh, O., Mewawalla, P., Shah, M. R., Saxena, A., Mahmoudjafari, Z., Snyder, J., Mushtaq, M. U., Kort, J., Habib, A., ... Khan, A. M. (2026). Sequencing BCMA-Directed Therapies in Relapsed/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies. Cancers, 18(19), 3147. https://doi.org/10.3390/cancers18193147

BCMA Targeted Therapies and Their Impact on Outcomes in Relapsed or Refractory Multiple Myeloma: Results From the French EMMY Cohort — European Journal of Haematology (September 2026)

What is the purpose of the study? 
The EMMY study evaluates how BCMA-targeted therapies were adopted and their real-world impact in patients with relapsed or refractory multiple myeloma (RRMM) receiving fourth or later lines of therapy (L4+) in France from 2017–2023.

Summary 
Among 1,362 patients treated in L4+, 294 (21.6%) received a BCMA-targeted regimen, with use increasing from 2.4% in 2019 to 52.0% in 2023, driven mainly by bispecific antibodies (BsAbs). Median time to next treatment (TTNT) increased from 8.0 to 12.1 months and median progression-free survival (PFS) from 7.2 to 9.3 months across treatment-initiation years; in L4, BCMA-targeted therapies were associated with longer TTNT (21.7 vs. 9.3 months; p=0.007) and PFS (13.4 vs. 7.9 months; p=0.015) than other regimens.

Key points 
• Population: 1,362 patients with RRMM receiving L4+ therapy across 73 French centers between 2017 and 2023. 
• BCMA-targeted therapy use: 294 patients (21.6%) received a BCMA-targeted regimen; use increased from 2.4% in 2019 to 52.0% in 2023, primarily because of BsAbs. 
• Overall outcomes: Median TTNT increased from 8.0 months (2017) to 12.1 months (2022), while median PFS increased from 7.2 to 9.3 months. 
• L4 comparison: BCMA-targeted therapy was associated with longer: 
 - TTNT: 21.7 vs. 9.3 months (p=0.007) 
 - PFS: 13.4 vs. 7.9 months (p=0.015) 
• Later treatment lines: Similar trends toward longer TTNT and PFS were observed in later lines (L4–L7). 
• Additional reported findings: The survival curves crossed at approximately 6 months, and the authors discussed primary non-response and initially restricted CAR T-cell access as possible explanations.

Strengths 
The study provides a national, longitudinal real-world perspective across multiple BCMA-targeted therapies and used a standardized EMMY data-collection process.

Limitations 
• No information on adverse events, quality of life, or healthcare resource utilization. 
• No adjusted comparative analyses were performed. 
• Comparisons between individual BCMA-targeted modalities were not feasible because of limited numbers, differences in availability and implementation, unequal follow-up, and potential confounding. 
• Real-world data had missing information and suboptimal data quality, although the authors state these were limited by the study design and standardized data collection. 
• Follow-up remains limited because BCMA-targeted therapies were only recently introduced in France; only 9.9% of patients were refractory to a prior BCMA-directed therapy.

Why this study matters 
The EMMY cohort documented rapid integration of BCMA-targeted therapies, particularly BsAbs, into real-world treatment of late-line RRMM in France between 2017 and 2023. BCMA-targeted regimens were associated with longer TTNT and PFS, including in L4 and later treatment lines, while the study lacked safety, quality-of-life, and healthcare-resource data and requires longer follow-up to evaluate treatment sequencing and longer-term outcomes.

Reference: 
T. Cazaubiel, O. Decaux, A. Perrot, et al., “BCMA Targeted Therapies and Their Impact on Outcomes in Relapsed or Refractory Multiple Myeloma: Results From the French EMMY Cohort,” European Journal of Haematology (2026): 1–10, https://doi.org/10.1111/ejh.70334.

 

Patient preferences for treatment‑free intervals in multiple myeloma: mixed‑methods insights on monitoring trade‑offs and supportive care improvements — Supportive Care in Cancer (October 2026)

What is the purpose of the study? 
To explore patient preferences regarding intervals between active treatment contacts, perceptions of monitoring, and treatment-related healthcare burdens among patients with multiple myeloma (MM). It also examines patient-generated proposals for improving inpatient and outpatient care.

Summary 
This 12-month, single-center mixed-methods survey included 100 patients with MM at a German tertiary center and assessed preferences for treatment-free intervals (TFIs), monitoring, relapse-risk trade-offs, inpatient stressors, and care improvements. Intervals between inpatient treatments were rated 10/10 by 49.0% of participants, 39.4% preferred a minimum interval of >8 weeks, and regular check-ups were reassuring for 77.0%; only 7.0% explicitly accepted higher relapse risk for longer TFIs. The most frequently reported inpatient stressors were separation from family (27.0%), treatment-related symptoms or side effects (23.0%), and fatigue (17.0%).

Key points 
• Treatment-free intervals: 49.0% rated intervals between inpatient treatments as 10/10 in importance; preferred minimum TFI length was heterogeneous, with 39.4% preferring >8 weeks. 
• Monitoring: Regular check-ups were described as reassuring by 77.0% and burdensome by 13.0%. 
• Relapse risk: 7.0% explicitly accepted a higher relapse risk in exchange for longer TFIs. 
• Inpatient stressors: The most frequently reported were: 
 - Separation from family: 27.0% 
 - Treatment-related symptoms or side effects: 23.0% 
 - Fatigue: 17.0%

• Qualitative findings: Patient narratives emphasized recovery, autonomy, reconnection with family, restoration of routines, and modifiable care-process factors.

• Care improvements proposed by patients: Quieter rooms, improved food quality, shorter waiting times, predictable scheduling, adequate staffing, empathetic communication, and access to light or low-intensity physical activity.

Strengths 
• Mixed-methods design
• Integration of structured responses with qualitative narratives
• Inclusion of patient-generated care-improvement proposals
• Item-specific denominators
• Exact 95% confidence intervals

Limitations 
• Single-center
• Cross-sectional design
• Limited generalizability
• Self-reported data with potential recall, social desirability, and classification biases
• Incomplete clinical and treatment-specific information
• Lack of inpatient-versus-outpatient stratified analysis
• Unvalidated study-specific questionnaire
• Limited precision for several response categories
• Inability to calculate a participation proportion or assess nonresponse bias
• Preferences may also change over time and may differ from decisions made under clinically defined risk-benefit conditions

Why this study matters 
In this single-center mixed-methods survey, participants with MM frequently valued intervals between active treatment contacts for recovery, autonomy, and restoration of daily routines, while regular monitoring was more often perceived as reassuring than burdensome. Preferences for TFI length were heterogeneous, and explicit willingness to accept higher relapse risk for longer intervals was uncommon. The findings are descriptive and do not establish the clinical safety or appropriateness of longer TFIs, treatment interruption, or changes to established therapy.

Reference: 
Fleischer, A., Barakat, M., Peter, J. et al. Patient preferences for treatment‑free intervals in multiple myeloma: mixed‑methods insights on monitoring trade‑offs and supportive care improvements. Support Care Cancer 34, 1050 (2026). https://doi.org/10.1007/s00520-026-11255-z

 

Gustatory dysfunction under talquetamab therapy in multiple myeloma: a cross-sectional study of patient-reported course, nutritional changes, and quality of life — Supportive Care in Cancer (October 2026)

What is the purpose of the study? 
To characterize patient-reported taste disturbances, recalled symptom course, nutritional changes, and quality of life in patients with relapsed/refractory multiple myeloma treated with talquetamab (TAL).

Summary 
This single-center, cross-sectional study evaluated 32 patients using taste-strip testing, a study-specific questionnaire, the EORTC QLQ-C30, and the PHQ-4. All patients reported taste disturbances during therapy; 71.9% reported onset within 14 days, and the median number of correctly identified taste strips was 2.5 (IQR 0.75–7.25), with eight patients having no correct identifications. Current appetite reduction was reported by 62.5% and was associated with lower mean taste-identification counts (2.45 vs. 7.83; mean difference −5.38, 95% CI −8.20 to −2.57; p=0.0006), while 50.0% reported directional weight loss and mean global health status was 50.5/100.

Key points 
• Taste disturbances: All 32 patients reported taste disturbances during TAL therapy; 23 (71.9%) recalled onset within 14 days. 
• Taste identification: The median identification count was 2.5 (IQR 0.75–7.25); 8 patients had no correct identifications. The study did not use a normative hypogeusia classification. 
• Appetite: 20 patients (62.5%) reported current appetite reduction. Their mean identification count was 2.45, compared with 7.83 among the other 12 patients (mean difference −5.38; 95% CI −8.20 to −2.57; p=0.0006). 
• Weight: 16 patients (50.0%) reported directional weight loss, with a median reported loss of 4.5 kg. 
• Quality of life: Mean global health status was 50.5/100 and was associated with taste-identification count (r=0.406; p=0.021). Role and social functioning had the lowest mean functioning scores. 
• Treatment cessation considerations: 10 patients (31.3%) had considered stopping talquetamab; 7 explicitly cited taste disturbance. Considering stopping treatment was not equivalent to missed doses, nonadherence, or treatment discontinuation. 
• Psychological symptoms: PHQ-4 results showed heterogeneous distress rather than uniformly high psychological morbidity. 
• Causality: The study did not establish that talquetamab caused the taste disturbances, appetite reduction, weight loss, or quality-of-life findings, nor did it establish a causal taste-to-appetite-to-weight pathway. 
• Recovery: The study could not establish sustained recovery because symptoms and improvement were recalled at a single assessment.

Strengths 
The analysis examined the within-cohort association between taste performance and appetite using both mean-based and rank-based analyses and distinguished symptom history, current impairment, and thoughts about stopping treatment.

Limitations 
Small, single-center sample; no pretreatment taste assessment or contemporaneous comparator; heterogeneous treatment stages; incomplete clinical and concomitant-treatment information; nonvalidated questionnaire coding; missing/unclassifiable impairment responses; recall limitations; absence of systematic measurements of olfaction, salivary function, detailed dietary intake, and body composition; multiple associations without multiplicity correction; and insufficient sample size for reliable confounder adjustment.

Why this study matters 
Among these 32 TAL-exposed patients, taste disturbances were reported by all participants, and lower recorded taste-identification counts were associated with current appetite reduction and lower global health status. The study also documented directional weight loss in half of the participants and explicit consideration of treatment cessation related to taste disturbance in seven patients, but its cross-sectional design and measurement limitations prevent estimation of norm-based hypogeusia prevalence, causal effects, sustained recovery, or effects on treatment adherence.

Reference: 
Fleischer, A., Burger, C., Roll, M. et al. Gustatory dysfunction under talquetamab therapy in multiple myeloma: a cross-sectional study of patient-reported course, nutritional changes, and quality of life. Support Care Cancer 34, 1059 (2026). https://doi.org/10.1007/s00520-026-11288-4

 
T-cell-redirecting therapies in early relapsed multiple myeloma: a systematic review and network meta-analysis — Journal of Hematology and Oncology (October 2026)

What is the purpose of the study? 
To evaluate whether randomized phase 3 evidence establishes a difference in efficacy among T-cell-redirecting therapies for early relapsed multiple myeloma (MM), using daratumumab-pomalidomide-dexamethasone (DPd)-type controls as the common comparator. It also descriptively examines safety, treatment sequencing, and drug-acquisition costs.

Summary 
This network meta-analysis included four randomized phase 3 trials involving 2,174 patients and evaluated ciltacabtagene autoleucel (cilta-cel), teclistamab-daratumumab, and talquetamab-daratumumab combinations, with or without pomalidomide, after at least one prior line of therapy. Control-arm median progression-free survival (PFS) ranged from 9.9 to 24.4 months (I²=91%); although fixed-effect analysis favored teclistamab-daratumumab for PFS, this difference was not maintained when between-trial heterogeneity was incorporated, and overall survival (OS) did not clearly differ between regimens. The authors concluded that the available randomized evidence does not establish an efficacy hierarchy or demonstrate equivalence among these regimens, while safety, sequencing, access, patient- and disease-related factors, and cost remain relevant considerations.

Key points 
• Population/evidence: Four randomized phase 3 trials comprising 2,174 patients with early relapsed MM after at least one prior line of therapy. 
• Regimens evaluated: Cilta-cel, teclistamab-daratumumab, and talquetamab-daratumumab with or without pomalidomide. 
• Control-arm variability: Median PFS in the predominantly daratumumab-pomalidomide-based control arms ranged from 9.9 to 24.4 months, with substantial heterogeneity (I²=91%). 
• PFS: Under a fixed-effect model, teclistamab-daratumumab ranked highest for PFS (P-score 98%) and had a hazard ratio of 0.55 (95% credible interval 0.34–0.88) versus talquetamab-daratumumab. After allowing for between-trial heterogeneity, the comparisons crossed unity; versus cilta-cel, the hazard ratio was 0.62 (95% credible interval 0.21–1.81). 
• OS: Results were concordant across models; teclistamab-daratumumab versus cilta-cel had a hazard ratio of 0.94 (95% credible interval 0.55–1.62). Restricted mean survival differences versus control at 24 months ranged from 0.7 to 1.6 months. 
• Safety: Toxicity profiles differed between modalities, but the overall toxicity burden could not be reliably compared across trials because of differences in follow-up, exposure, and safety ascertainment. 
• Cost: Using a population-standardized denominator, modeled cost per PFS month was lowest for cilta-cel. The analysis used US drug-acquisition/wholesale acquisition costs and was not a cost-effectiveness analysis.

Strengths  
The study reported fixed- and random-effects estimates side by side to examine dependence on the heterogeneity assumption and re-estimated comparisons using a frequentist graph-theoretical model as a robustness check.

Limitations 
• The analysis was an anchored indirect comparison rather than a head-to-head randomized trial and depended on transitivity and absence of effect-modifier imbalance. 
• The network had a star structure with no direct comparisons between experimental regimens and no closed loops to assess consistency. 
• Each network edge was based on a single trial, preventing empirical estimation of between-trial heterogeneity. 
• Patient-level time-to-event data were reconstructed from published survival curves when necessary, which could introduce reading error. 
• Trials differed in eligibility, prior treatment exposure, control regimens, follow-up, and handling of patients who did not receive cilta-cel. 
• Safety, sequencing, and cost analyses were descriptive rather than anchored comparative analyses. 
• The use of wholesale/list prices without present-value adjustment and exclusion of broader resource use limited interpretation of the cost analysis. 
• The authors characterized the analyses as hypothesis-generating, not substitutes for individual-patient-data meta-analysis or randomized comparisons.

Why this study matters 
Available randomized evidence in early relapsed MM does not establish an efficacy hierarchy or demonstrate equivalence among cilta-cel, teclistamab-daratumumab, and talquetamab combinations. Fixed-effect estimates favored teclistamab-daratumumab for PFS, but this separation was not robust to between-trial heterogeneity, while OS did not clearly separate; therefore, treatment selection cannot be based on comparative efficacy data alone and also involves patient- and disease-related factors, toxicity, sequencing, access, and cost.

Reference: 
Merz, M., Souto Filho, J.T., Voorhees, P.M. et al. T-cell-redirecting therapies in early relapsed multiple myeloma: a systematic review and network meta-analysis. J Hematol Oncol 19, 83 (2026). https://doi.org/10.1186/s13045-026-01850-2

Dual targeting of BCMA and GPRC5D with the trispecific antibody ramantamig addresses antigenic heterogeneity in myeloma — HemaSphere (October 2026)

What is the purpose of the study? 
To evaluate whether ramantamig (JNJ-79635322), a trispecific antibody that simultaneously targets BCMA and GPRC5D on multiple myeloma (MM) cells, could overcome heterogeneous antigen expression and reduce resistance associated with loss of a single target. Its activity was compared with BsAbs targeting BCMA or GPRC5D alone and with the combination of the two mono-targeting BsAbs.

Summary 
The study found marked interpatient and intratumor heterogeneity in BCMA and GPRC5D expression among MM cells. In cell-line and ex vivo bone marrow (BM) experiments, ramantamig produced greater MM-cell lysis than BCMA- or GPRC5D-mono-targeting BsAbs and also showed greater activity than the combination of the two mono-targeting BsAbs; in 32 patient BM samples, mean lysis with 0.4 nM ramantamig was 60%, compared with 13% and 5% for BCMA- and GPRC5D-targeting controls, respectively. Ramantamig activity was observed in samples from both newly diagnosed and heavily pretreated, BsAb-naïve patients, was less affected by soluble BCMA than the BCMA-mono-targeting control, and was greater when a higher proportion of MM cells expressed both antigens.

Key points 
• Target heterogeneity: BCMA and GPRC5D expression varied both between patients and within individual tumors; single-antigen-positive and double-negative MM-cell populations were also identified.

• Ex vivo activity: In 32 BM samples, ramantamig at 0.4 nM produced a mean MM-cell lysis of 60%, versus 13% with the BCMA-mono-targeting BsAb and 5% with the GPRC5D-mono-targeting BsAb.

• Activity across disease/treatment status: No difference in ramantamig-mediated MM-cell lysis was observed between samples from newly diagnosed and heavily pretreated, BsAb-naïve patients.

• Effect of antigen expression: Higher baseline proportions of BCMA/GPRC5D double-positive MM cells were associated with greater ex vivo tumor-cell lysis, T-cell activation, and T-cell degranulation.

• Single-antigen populations: In vitro, ramantamig showed activity against MM cell lines with very low or negative expression of either BCMA or GPRC5D and was evaluated in a relapse model containing a BCMA-negative tumor population.

• Soluble BCMA: Soluble BCMA had only a modest effect on ramantamig activity, whereas it substantially impaired the BCMA-mono-targeting control.

• Comparison with combined BsAbs: Ramantamig produced greater MM-cell lysis than the combination of separate BCMA- and GPRC5D-targeting BsAbs in cell-line and ex vivo assays.

• Clinical data reported in the discussion: Preliminary data from an ongoing phase 1 study in heavily pretreated MM reported a 100% ORR and 89% CR among 27 patients naïve to BCMA/GPRC5D-directed therapies treated at the recommended phase 2 dose, with 93% PFS at 12 months. The authors state that longer follow-up and larger patient numbers are needed.

Strengths
The study focused on ex vivo efficacy using fully autologous BM samples, and the authors note that ex vivo sensitivity has previously correlated with clinical response to other immunotherapies, including daratumumab, teclistamab, and talquetamab.

Limitations  
• Only short-term cytotoxicity assays were performed, and durability of response was not evaluated in mouse models. 
• Baseline T-cell fitness and the immunosuppressive microenvironment, in addition to antigen heterogeneity, may affect sustained clinical response and require further investigation. 
• Measurement limitation: The authors could not exclude the possibility that some apparently double-negative tumor cells had BCMA or GPRC5D expression below the detection limit of flow cytometry.

Why this study matters 
Ramantamig demonstrated greater cytotoxic activity than BsAbs targeting BCMA or GPRC5D individually and than their combination in MM cell lines and 32 patient-derived BM samples with heterogeneous antigen expression. The findings support further clinical investigation of simultaneous BCMA/GPRC5D targeting, while the study's short-term ex vivo design does not establish the durability of clinical responses.

Reference: 
O'Neill, C., Broekmans, M.E.C., Korst, C.L.B.M., Krevvata, M., Dal Collo, G., Groen, R.W., Li, B., Baglio, S.R., Philippar, U., Pillarisetti, K., Zweegman, S., Vishwamitra, D., Mutis, T. and van de Donk, N.W.C.J. (2026), Dual targeting of BCMA and GPRC5D with the trispecific antibody ramantamig addresses antigenic heterogeneity in myeloma. HemaSphere, 10: e70487. https://doi.org/10.1002/hem3.70487

Clinical Trials

New Data from Phase 3 MajesTEC-3 Trial Show Sustained Survival Benefit from Teclistamab Plus Daratumumab in Early Line Treatment for Relapsed/Refractory Myeloma — Johnson & Johnson

What is the purpose of the study? 
The Phase 3 MajesTEC-3 (NCT05083169) trial evaluates teclistamab plus daratumumab (Tec-Dara) versus investigator’s choice of DPd/DVd in adults with relapsed/refractory multiple myeloma (RRMM) who have received one to three prior lines of therapy. The study assesses progression-free survival and other outcomes, including overall survival, response, minimal residual disease, symptoms, and safety.

Summary 
In observed MajesTEC-3 data, 36-month overall survival was 83.3% with Tec-Dara versus 65.0% with DPd/DVd (HR 0.46; 95% CI, 0.32–0.65; P<0.0001). A post hoc competing-risk analysis found disease progression at 36 months in 8.7% versus 62.1%, respectively (sHR 0.10; 95% CI, 0.07–0.16; P<0.0001), while non-relapse mortality did not differ significantly (10.2% vs 9.0%; sHR 1.16; 95% CI, 0.69–1.98; P=0.5668).

A statistical relative survival mixture cure model estimated an 86.6% overall-survival cure fraction with Tec-Dara and projected 18.5 years of remaining life expectancy, compared with 4.9 years with DPd/DVd and 21.1 years for an age-matched general population; these are model-based projections from an ongoing trial and are not observed long-term survival outcomes.

Key points 
• Design: Randomized, ongoing Phase 3 MajesTEC-3 trial; NCT05083169. 
• Population: Adults with RRMM after one to three prior lines of therapy. 
• Treatment: Tec-Dara versus investigator’s choice of DPd or DVd. 
• Overall survival: 36-month OS was 83.3% vs 65.0%; HR 0.46 (95% CI, 0.32–0.65; P<0.0001). 
• Disease progression: 36-month cumulative incidence was 8.7% vs 62.1%; sHR 0.10 (95% CI, 0.07–0.16; P<0.0001). 
• Non-relapse mortality: 10.2% vs 9.0% at 36 months; difference was not statistically significant. 
• Model-based survival: Estimated OS cure fraction was 86.6% with Tec-Dara versus 0% with DPd/DVd, with greater uncertainty for the latter estimate. 
• Model-based life expectancy: Projected at 18.5 years with Tec-Dara versus 4.9 years with DPd/DVd; age-matched general population projection was 21.1 years. 
• Limitations: The long-term survival estimates are statistical projections from an ongoing trial; continued follow-up is needed to compare these projections with observed long-term survival. 
• Safety: Teclistamab has a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, including ICANS. In MajesTEC-3, serious infections occurred in 54% of patients receiving Tec-Dara at the recommended dosage, with fatal infections in 4.6%.

Why this study matters 
Observed MajesTEC-3 results showed higher 36-month overall survival and substantially lower disease progression with Tec-Dara than with DPd/DVd, while non-relapse mortality was not significantly different between groups. The projected long-term survival estimates remain model-based, and the ongoing trial requires further follow-up to determine how closely those projections correspond to observed outcomes.

References: 
New model-based analysis further supports the potential of TECVAYLI® (teclistamab-cqyv) plus DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) to redefine long-term survival expectations in early line relapsed/refractory multiple myeloma. Johnson & Johnson press release. September 23, 2026.
 

Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS — Journal of Clinical Oncology (September 2026)

What is the purpose of the study? 
The phase III CEPHEUS trial (NCT03652064) evaluates the efficacy and safety of daratumumab plus bortezomib, lenalidomide, and dexamethasone (DVRd) versus VRd in patients with transplant-ineligible (TIE) or transplant-deferred newly diagnosed multiple myeloma (NDMM). This analysis specifically assesses outcomes in the TIE subgroup.

Summary 
In the TIE subgroup (N=289), after a median follow-up of 58.7 months, MRD negativity at 10⁻⁵ was 60.4% with DVRd versus 39.3% with VRd (P=.0004), with higher rates of sustained MRD negativity for ≥12 and ≥24 months with DVRd. Progression-free survival (PFS) was significantly improved with DVRd, with a 49% lower risk of disease progression or death (HR, 0.51; 95% CI, 0.35–0.74; P=.0003); overall survival favored DVRd but remained immature (HR, 0.66; 95% CI, 0.42–1.03), and adverse events were consistent with known safety profiles.

Key points 
• Population: 289 patients with TIE NDMM; DVRd, n=144; VRd, n=145. 
• MRD negativity (10⁻⁵): 60.4% with DVRd vs 39.3% with VRd (P=.0004). 
• Sustained MRD negativity (10⁻⁵): 
 - ≥12 months: 47.2% vs 28.3% (P=.0010) 
 - ≥24 months: 40.3% vs 22.8% (P=.0015)

• PFS: HR 0.51 (95% CI, 0.35–0.74; P=.0003). 
• Overall survival: HR 0.66 (95% CI, 0.42–1.03); the analysis was described as immature. 
• Approximately 25% of patients receiving DVRd reduced to weekly bortezomib dosing; the study reported that this did not appear to affect PFS outcomes. 
• Safety: Adverse events were consistent with known safety profiles. COVID-related grade 5 adverse events were higher with DVRd, whereas non-COVID-related grade 5 adverse events and exposure-adjusted grade 5 event rates were very similar between treatment groups.

Limitation/qualification
Cross-trial comparisons with the IMROZ trial must be interpreted with caution.

The authors noted that identifying patients most vulnerable to infectious complications during anti-CD38-based therapy remains an important research priority.

Why this study matters 
In the CEPHEUS TIE subgroup, DVRd produced higher rates of MRD negativity and sustained MRD negativity and significantly improved PFS compared with VRd. Overall survival favored DVRd but remained immature, while safety findings were consistent with the reported CEPHEUS population, including higher COVID-related grade 5 adverse events in the DVRd group.

Reference: 
Saad Z. Usmani et al. Daratumumab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Transplant-Ineligible Subgroup Analysis of CEPHEUS. J Clin Oncol 0, JCO-26-00401 DOI:10.1200/JCO-26-00401

New Data from 5-Year CARTITUDE-2 Cohort Showed 69.2% Overall Survival Rate in Half of Patients with Relapsed/Refractory Myeloma After Single Infusion of Cilta-cel — Legend Biotech (September 2026)

What is the purpose of the study? 
The study evaluates the long-term safety and efficacy of Carvykti® (ciltacabtagene autoleucel; cilta-cel) in patients with relapsed/refractory multiple myeloma (RRMM) who had received one to three prior lines of therapy. The report presents five-year follow-up data from CARTITUDE-2 Cohort A after a single cilta-cel infusion.

Summary 
In CARTITUDE-2 Cohort A (n=20), with a median follow-up of 60.7 months, the median progression-free survival (PFS) was 60.5 months, median overall survival (OS) was not reached, and 69.2% of patients were alive at five years. At five years, 10 of 20 patients (50%) remained alive and progression-free without maintenance or further anti-myeloma treatment after a single CARVYKTI infusion. With longer follow-up, the safety profile remained consistent with the known safety profile of CARVYKTI, with no new CAR T-cell-related neurotoxicity reported; one patient developed acute myeloid leukemia and two deaths occurred, due to progressive disease and new cancer.

Key points 
• Study: CARTITUDE-2 Cohort A (NCT04133636), an ongoing Phase 2 multicohort study. 
• Population: 20 patients with RRMM who had received 1–3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, and were lenalidomide-refractory.
• Follow-up: Median 60.7 months
• Median PFS: 60.5 months. 
• Median OS: Not reached at the time of analysis. 
• Five-year OS: 69.2%. 
• Five-year progression-free and treatment-free status: 10/20 patients (50%) remained alive and progression-free without further anti-myeloma treatment. 
• Safety: The longer-term safety profile was consistent with the known safety profile of cilta-cel; no new CAR T-cell-related neurotoxicity was reported. 
• Events reported since the approximately 30-month analysis: One new hematologic malignancy (acute myeloid leukemia) and two deaths, attributed to progressive disease and new cancer. 
• Study endpoint: The primary endpoint for Cohort A was minimal residual disease (MRD) negativity.

Why this study matters 
At a median follow-up of 60.7 months, half of the 20 patients in CARTITUDE-2 Cohort A remained alive and progression-free without further anti-myeloma treatment five years after a single cilta-cel infusion. Median PFS was 60.5 months, median OS had not been reached, and 69.2% of patients were alive at five years; longer-term safety findings were consistent with the known safety profile, with no new CAR T-cell-related neurotoxicity reported.

Reference: 
Legend Biotech Presents CARVYKTI Data Showing Half of Patients with RRMM Remained Progression-Free and Alive Five Years After a Single Infusion. Legend Biotech press release. September 25, 2026.

Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial — The Lancet Oncology (September 2026)

What is the purpose of the study? 
The study evaluates whether iberdomide + daratumumab + dexamethasone improves minimal residual disease (MRD)-negative complete response compared with daratumumab + bortezomib + dexamethasone in adults with relapsed or refractory multiple myeloma. Progression-free survival is the second primary endpoint and remains under assessment.

Summary 
EXCALIBER-RRMM is an ongoing, open-label, randomised, phase 3 trial conducted at 211 sites in 31 countries. Among the first 420 patients assessed after a median follow-up of 15.7 months, MRD-negative complete response occurred in 41% (85/207) of patients receiving iberdomide, daratumumab, and dexamethasone versus 21% (44/213) receiving daratumumab, bortezomib, and dexamethasone (stratified proportion difference 20.1%, 95% CI 11.5–28.6; p<0.0001; OR 2.8, 95% CI 1.8–4.3). Grade 3 or 4 adverse events occurred in 92% versus 70%, respectively, with neutropenia and infection more frequent in the iberdomide group.

Key points 
• Study: EXCALIBER-RRMM, phase 3, open-label, randomised, controlled trial; ClinicalTrials.gov NCT04975997. 
• Population: Adults with relapsed or refractory multiple myeloma after 1–2 previous lines of therapy who had subsequently experienced disease progression. 
• Primary MRD analysis: 420 patients; 207 received iberdomide + daratumumab + dexamethasone and 213 received daratumumab + bortezomib + dexamethasone. 
• MRD-negative complete response: 41% vs 21%; stratified proportion difference 20.1% (95% CI 11.5–28.6; p<0.0001). 
• Grade 3/4 adverse events: 92% vs 70%. 
• Neutropenia: 84% vs 11%; infection: 39% vs 22%. 
• Serious adverse events: 58% vs 41%; pneumonia was the most common serious adverse event (18% vs 6%). 
• Treatment-related deaths as assessed by investigators: 3 (1%) vs 2 (1%). 
• Study limitation/status: Progression-free survival, the second dual primary endpoint, was still ongoing at the time of this analysis.

Why this study matters 
In the primary MRD analysis, iberdomide, daratumumab, and dexamethasone produced a higher proportion of MRD-negative complete responses than daratumumab, bortezomib, and dexamethasone. Grade 3 or 4 adverse events, including neutropenia and infections, occurred more frequently with the iberdomide regimen, while progression-free survival assessment was ongoing.

Reference: 
Lonial S, Dimopoulos MA, Gavriatopoulou M, Kim K, Min CK, Oriol A, Moreira CCC, Quach H, Qiu L, Xia Z, Schjesvold F, Casas-Avilés I, Xu Y, Hungria V, Seval GC, Fang B, Kyriakou C, Prince HM, Zhuang J, Lin HC, Mateos MV, Špička I, Maiolino A, Vural F, Basu S, Dytfeld D, Fu C, Ho PJ, Joseph N, Low M, Pour L, Girnius S, Berdeja JG, Otero PR, Cheng Y, Amatangelo M, Hersey S, Kazanecki C, Weisskopf MB, Kyada MJ, Abad PC, Chu S, Morando J, Maciag P, Richardson PG, van de Donk NW; EXCALIBER-RRMM Investigators. Iberdomide plus daratumumab and dexamethasone versus daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory multiple myeloma (EXCALIBER-RRMM): an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2026 Sep 25:S1470-2045(26)00450-X. doi: 10.1016/S1470-2045(26)00450-X.  

Additional Information

Phase 3 EXCALIBER-RRMM Trial Results: Zenbexus (Iberdomide) in Combination with Daratumumab and Dexamethasone Showed Longer Progression-Free Survival vs Standard of Care in Relapsed/Refractory Myeloma — Bristol Myers Squibb

Summary 
EXCALIBER-RRMM was a randomized, open-label, multicenter Phase 3 trial in 800 adults with multiple myeloma and progressive disease after one to two prior lines of therapy; treatment continued until disease progression or unacceptable toxicity. At a median follow-up of 23 months, median progression-free survival (PFS) was 42 months with ZDd versus 20 months with DVd (hazard ratio [HR], 0.49; p<0.000001), representing the reported statistically significant result for one of the study's two dual-primary endpoints. The other dual-primary endpoint, minimal residual disease (MRD)-negative complete response, had previously shown a significant benefit for ZDd; the study also evaluates overall survival, overall response rate, safety and sustained MRD negativity.

Key points

• Population: 800 adults with relapsed or refractory multiple myeloma who had received one to two prior lines of anti-myeloma therapy and had progressive disease. 
• Treatment comparison: ZDd (iberdomide + daratumumab + dexamethasone) versus DVd (daratumumab + bortezomib + dexamethasone). 
• PFS: Median PFS was 42 months with ZDd versus 20 months with DVd. 
• Effect estimate: HR 0.49, with p<0.000001; the reported result corresponds to a 51% reduction in the risk of disease progression or death with ZDd compared with DVd. 
• Follow-up: Median follow-up was 23 months. 
• Other primary endpoint: MRD-negative complete response had previously demonstrated a significant benefit for ZDd and supported FDA accelerated approval of Zenbexus for certain patients with relapsed or refractory multiple myeloma. 
• Safety: The reported safety profile was consistent with previously reported findings. In the iberdomide-containing regimen, venous thromboembolic events occurred in 6.4%, arterial thromboembolic events in 3.4%, all-grade neutropenia in 90.2% (Grade 3: 30.9%; Grade 4: 53.4%), and febrile neutropenia in 5.4%. 
• Infections: Infections occurred in 78.9%, including Grade 3 infections in 35.8%, Grade 4 infections in 3.4%, and fatal infections in 2%; serious infections occurred in 40%. 
• Serious adverse reactions: Occurred in 58.3% of patients receiving Zenbexus. Common adverse reactions occurring in at least 20% include upper respiratory tract infection, fatigue, musculoskeletal pain, pneumonia, diarrhea, motor dysfunction, rash, sleep disorders, hypogammaglobulinemia, COVID-19 and constipation. 
• Important safety warnings: Zenbexus carries boxed warnings for embryo-fetal toxicity and serious venous and arterial thromboembolic events and is contraindicated during pregnancy. 
• Regulatory status: The current U.S. indication for Zenbexus with daratumumab and hyaluronidase-fihj plus dexamethasone is for adults with multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. The indication was granted under FDA accelerated approval based on MRD-negative complete response at any time.

ZDd showed significant improvement in PFS vs DVd 
In EXCALIBER-RRMM, ZDd was associated with a statistically significant improvement in PFS compared with DVd, with median PFS of 42 versus 20 months and an HR of 0.49 at a median follow-up of 23 months. The iberdomide-containing regimen was also associated with substantial rates of neutropenia, infections, thromboembolic events and serious adverse reactions, while the study's other dual-primary endpoint, MRD-negative complete response, had previously shown a significant benefit.

Reference: 
Bristol Myers Squibb Announces ZENBEXUS (iberdomide) in Combination with Daratumumab and Dexamethasone (ZDd) Demonstrates Superior Progression-Free Survival vs. Standard of Care in Relapsed and Refractory Multiple Myeloma in Phase 3... BMS press release. October 8, 2026.

Daratumumab ± pomalidomide maintenance after salvage autologous transplantation in relapsed multiple myeloma: a phase 2 study — Blood Cancer Journal (September 2026)

What is the purpose of the study? 
To evaluate daratumumab (DARA), with or without pomalidomide (POM), as maintenance therapy after salvage or delayed autologous stem cell transplantation (ASCT) in adults with relapsed/refractory multiple myeloma (RRMM). The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS), response, measurable residual disease (MRD) negativity, and safety.

Summary 
This open-label, single-center, single-arm phase 2 trial (ClinicalTrials.gov NCT03622775) enrolled 13 patients with RRMM who had undergone salvage or delayed ASCT; 11 received DARA-POM and 2 received DARA alone. After a median follow-up of 48.5 months from maintenance initiation, median PFS was 45.1 months (95% CI, 26.3–not reached), median OS was not reached, and 4-year PFS and OS from ASCT were 62% and 100%, respectively. During maintenance, the proportion achieving complete response (CR) or better increased from 46% to 85%, while 6 of 8 evaluable patients (75%) were MRD-negative at 6 months; grade ≥3 neutropenia occurred in 62% and grade ≥3 bacterial or viral infections in 31%.

Key points 
• Study design: Open-label, single-center, single-arm phase 2 study at The University of Texas MD Anderson Cancer Center. 
• Population: 13 adults with RRMM; median age at salvage/delayed ASCT was 64 years; patients had received a median of 2 prior lines of therapy. 
• Treatment: DARA 1800 mg subcutaneously according to a 28-day-cycle schedule, with POM 2 mg orally on days 1–21 for patients receiving combination therapy. 
• Treatment distribution: 2 patients (15%) received DARA alone and 11 (85%) received DARA-POM. 
• Efficacy: 
 - Median PFS from maintenance initiation: 45.1 months (95% CI, 26.3–NR). 
 - Median OS: NR (95% CI, 51.1–NR). 
 - 4-year PFS from salvage/delayed ASCT: 62% (95% CI, 35–88). 
 - 4-year OS from salvage/delayed ASCT: 100%. 
 - CR or better increased from 46% at maintenance initiation to 85% at final response evaluation. 
 - 5 of 7 (71%) patients entering maintenance below CR subsequently achieved ≥CR. 
 - 6 of 8 (75%) patients with evaluable MRD data were MRD-negative at 6 months at the 10⁻⁵ sensitivity level.

• Safety: 
 - Most common grade ≥3 toxicity: neutropenia (62%). 
 - Grade ≥3 bacterial or viral infections: 31%. 
 - Other cytopenias were grade 1–2; fatigue and diarrhea were grade 1–2.

Strengths/limitations 
• Early termination because of slow accrual resulted in a small sample size, limiting statistical precision and generalizability. 
• The single-center, nonrandomized design further limited these considerations. 
• The protocol amendment allowing POM created treatment heterogeneity and prevented regimen-specific comparisons. 
• The exploratory 10-year RMST analysis may have limited estimate stability because of the small number of deaths and follow-up that was modestly shorter than the truncation horizon. 
• MRD data were available for only a subset, and inconsistent longitudinal testing prevented assessment of sustained MRD negativity.

Why this study matters 
In this 13-patient phase 2 study, DARA-based maintenance following salvage or delayed ASCT in RRMM was associated with a median PFS of 45.1 months, increasing CR-or-better responses to 85%, and MRD negativity at 6 months in 75% of evaluable patients. The findings were reported in the context of substantial limitations, including early study closure, small sample size, single-center nonrandomized design, treatment heterogeneity after protocol amendment, and incomplete longitudinal MRD assessment.

Reference: 
Pasvolsky, O., Costa, B.A., Aljawai, Y.M. et al. Daratumumab ± pomalidomide maintenance after salvage autologous transplantation in relapsed multiple myeloma: a phase 2 study. Blood Cancer J. 16, 163 (2026). https://doi.org/10.1038/s41408-026-01620-w

Longitudinal assessments of MRD in high-risk newly diagnosed transplant-ineligible multiple myeloma in the BENEFIT study (IFM2020-05) — HemaSphere (October 2026)

What is the purpose of the study? 
The BENEFIT study evaluates whether adding the proteasome inhibitor bortezomib to isatuximab + lenalidomide + dexamethasone (Isa-VRd), compared with isatuximab + lenalidomide + dexamethasone (IsaRd), improves minimal residual disease (MRD) outcomes in patients with newly diagnosed multiple myeloma who were transplant-ineligible (NDMM TI). This analysis specifically assesses MRD negativity and safety in patients with high-risk multiple myeloma (HRMM) defined using the International Myeloma Society/International Myeloma Working Group (IMS/IMWG) genomic consensus staging (GCS) definition.

Summary 
BENEFIT was a Phase 3 randomized trial sponsored by CHU Poitiers, France, in collaboration with the Intergroupe Francophone du Myélome (IFM), enrolling patients aged 65–79 years with NDMM TI who received Isa-VRd or IsaRd until progression. MRD was centrally assessed by next-generation sequencing (NGS) at sensitivities of 10⁻⁵ and 10⁻⁶ at 12, 18, and 24 months and annually thereafter in patients achieving at least a partial response; three patients were assessed by multiparametric flow cytometry (MFC) at 10⁻⁵ and classified as 10⁻⁶-positive when they were 10⁻⁵-negative.

Among 270 patients, 72 (27%) met the GCS definition of HRMM, including 42/135 (31%) in the Isa-VRd group and 30/135 (22%) in the IsaRd group. The GCS definition reclassified 49 patients (20%) as HRMM compared with the previous Intergroupe Francophone du Myélome linear predictor (IFM-LP) cytogenetic score classification. At 18 months, MRD negativity at 10⁻⁵ was 50% with Isa-VRd versus 27% with IsaRd in HRMM (OR 2.75, 95% CI 1–7; P=0.049); at 10⁻⁶, the corresponding rates were 45% versus 27% (OR 2.27, 95% CI 0.8–6; P=0.011).

With a median follow-up of 33.4 months (95% CI 33–34), sustained MRD negativity (sMRD ≥12 months) at 10⁻⁵ was 34% with Isa-VRd versus 16% with IsaRd overall (OR 2.73, 95% CI 1.5–4.8; P=0.0007), and 31% versus 13% in HRMM (OR 2.91, 95% CI 0.8–10; P=0.09). Survival data remained immature at this follow-up duration.

Key points 
• Population: 270 patients with NDMM TI aged 65–79 years; 72 (27%) were HRMM according to GCS. 
• Treatment: Isa-VRd versus IsaRd until disease progression. 
• MRD assessment: Primarily NGS at 10⁻⁵ and 10⁻⁶ sensitivity; sMRD was defined as MRD negativity maintained for at least 12 months without an intervening positive result.

• 18-month MRD negativity at 10⁻⁵ in HRMM: 
 - Isa-VRd: 50% (21/42; 95% CI 34–66) 
 - IsaRd: 27% (8/30; 95% CI 12–46) 
 - OR 2.75 (95% CI 1–7); P=0.049

• 18-month MRD negativity at 10⁻⁶ in HRMM: 
 - Isa-VRd: 45% (19 patients; 95% CI 30–61) 
 - IsaRd: 27% (8 patients; 95% CI 12–46) 
 - OR 2.27 (95% CI 0.8–6); P=0.011

• Overall sMRD ≥12-month negativity at 10⁻⁵: 34% with Isa-VRd versus 16% with IsaRd (OR 2.73, 95% CI 1.5–4.8; P=0.0007). 
• Overall sMRD ≥12-month negativity at 10⁻⁶: 21% versus 7% (OR 3.19, 95% CI 1.5–6.9; P=0.003). 
• HRMM sMRD ≥12-month negativity at 10⁻⁵: 31% with Isa-VRd versus 13% with IsaRd (OR 2.91, 95% CI 0.8–10; P=0.09), so the reported difference was not statistically significant. 
• GCS versus IFM-LP: GCS classified 49 additional patients (20%) as HRMM compared with the earlier IFM-LP classification. 
• Early progression: 24 patients progressed within 18 months of treatment initiation. Eleven (4% of the cohort) had not initially been classified as HRMM; 5 were in the Isa-VRd group and 6 in the IsaRd group. None achieved MRD negativity at 10⁻⁵. 
• Safety: Adverse events occurring in ≥10% of patients were not different between HRMM and non-HRMM groups. There were 169 grade ≥2 adverse events resulting in temporary or permanent bortezomib discontinuation in 78 patients, including 57 (56%) in non-HRMM and 21 (64%) in HRMM. 
• Second primary malignancies: 23 solid-tumor second primary malignancies occurred in 19 patients (7%), with no difference between treatment arms or according to HRMM status.

• Dose intensity: Median relative dose intensity was maintained similarly in HRMM and non-HRMM groups, including for bortezomib. 
• MRD over time: In the overall Isa-VRd group, MRD negativity at 10⁻⁵ decreased from 53% at 18 months to 44% at 24 months. The decrease was similar in HRMM (50% to 40%) and non-HRMM (54% to 45%). 
• Bortezomib schedule: In BENEFIT, bortezomib was administered weekly for 18 months, with twice-monthly administration during cycles 13–18, and was stopped at 18 months. The study notes that IMROZ and CEPHEUS used twice-weekly bortezomib for 6 months and that sMRD rates at 24 months were similar across these studies; the authors state that future studies will need to validate whether there is an optimal schedule in HRMM. 
• t(11;14): Patients with t(11;14) multiple myeloma had lower MRD-negativity rates through 24 months despite not having a high-risk disease profile. The study reports that this subgroup may respond more slowly or may require specific treatment approaches; these observations were reported without corresponding detailed numerical data. 
• Study-reported observation: Among GCS-defined HRMM patients, Isa-VRd showed higher MRD-negativity rates than IsaRd at the assessed time points, although some subgroup comparisons were not statistically significant.

Limitations 
Survival remained immature at a median follow-up of 33.4 months. Some HRMM subgroup analyses involved limited numbers of patients, and several differences therefore did not reach statistical significance.

Why this study matters 
In BENEFIT, adding bortezomib to IsaRd as Isa-VRd was associated with higher MRD-negativity rates than IsaRd in NDMM TI patients, including those classified as HRMM by GCS. In HRMM, the 18-month MRD-negativity rate at 10⁻⁵ was 50% with Isa-VRd versus 27% with IsaRd, while the difference in sustained MRD negativity was not statistically significant; survival outcomes remain immature. The study also reports a decline in MRD negativity after bortezomib was stopped at 18 months, and future studies will need to validate whether there is an optimal bortezomib schedule in HRMM.

Reference:  
Corre, J., Lambert, J., Bobin, A., Manier, S., Perrot, A., Karlin, L., Roussel, M., Bigot, N., Benbrahim, O., Allangba, O., Rey, P., Dorvaux, V., Vignon, M., Roland, V., Garidi, R., Bastie, J.-N., Chretien, M.-L., Godet, S., Montes, L., Cherel, B., Vekhoff, A., Chalopin, T., Slama, B., Laribi, K., Dingremont, C., Roul, C., Richez-Olivier, V., Mariette, C., Rigaudeau, S., Calmettes, C., Dib, M., Tiab, M., Vincent, L., Delaunay, J., Maheo, S., Schavgoulidze, A., Frenzel, L., Godmer, P., Calloch, R.L., Chalayer, E., Gardeney, H., Macro, M., Royer, B., Harel, S., Decaux, O., Arnulf, B., Belhadj, K., Gontier, A., Touzeau, C., Mohty, M., Moreau, P., Facon, T., Hulin, C. and Leleu, X. (2026), Longitudinal assessments of MRD in high-risk newly diagnosed transplant-ineligible multiple myeloma in the BENEFIT study (IFM2020-05). HemaSphere, 10: e70482. https://doi.org/10.1002/hem3.70482
 
 

Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma — Nature Medicine (October 2026)

What is the purpose of the study? 
To evaluate the long-term safety, response durability, and clinical outcomes of in vivo BCMA-targeted CAR-T therapy (ESO-T01) in patients with relapsed/refractory multiple myeloma (R/R MM). It provides follow-up data for four patients previously reported with up to 3 months of follow-up, extending the maximum follow-up to 15 months.

Summary 
Four patients with R/R MM received ESO-T01, an in vivo BCMA-targeted CAR-T therapy, without leukapheresis or lymphodepletion. All four patients achieved an objective response; one maintained stringent complete response (sCR) for 15 months, while three experienced relapse or progression, all with extramedullary involvement. The median progression-free survival (PFS) was 4.0 months (range, 3.0–15.0), and no immunogenicity- or integration-related toxicities or new important ESO-T01-related adverse events were identified beyond the initial report.

Key points

Treatment and follow-up 
• Four patients with R/R MM received ESO-T01 without leukapheresis or lymphodepletion. 
• Maximum follow-up was 15 months. 
• The previously reported safety findings included dual-phase cytokine release syndrome (CRS), grades 1–3, and grade ≥3 hematotoxicities in all patients; one patient had grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). 
• During extended follow-up, no immunogenicity- or integration-related toxicities and no new important ESO-T01-related adverse events were reported.

Clinical outcomes 
• Objective response rate: 100% (4/4 patients) in the initial report: two sCRs and two partial responses. 
• One patient maintained sCR for 15 months. 
• Three patients experienced relapse or disease progression, all involving extramedullary disease; all three eventually died during follow-up. 
• Median PFS was 4.0 months (range, 3.0–15.0 months). 
• Following progression, salvage treatments were associated with overall survival of 5.5–10.9 months after infusion. 
• One patient who progressed after in vivo CAR-T subsequently received ex vivo CAR-T and achieved a very good partial response (VGPR).

CAR-T persistence and disease relapse 
• The authors observed limited persistence of in vivo CAR-T cells overall. 
• The patient with the 15-month sCR had a second CAR-T expansion detected by qPCR at month 3 and predominantly naive and central-memory CAR-T phenotypes. 
• Three patients with relapse/progression had extramedullary involvement; the authors report that the mechanisms underlying this pattern remain incompletely understood. 
• BCMA-dim and BCMA-negative expression was documented in biopsies from one patient at relapse, while BCMA status was unavailable for the other two patients with extramedullary disease.

Immune and hematologic findings 
• A rapid “lymphocyte disappearance” occurred within hours after infusion and was accompanied by fever and chills; neutrophil and platelet counts remained unchanged. 
• The authors considered several possible mechanisms for this phenomenon, with cytokine/chemokine-driven migration considered more likely based on their measurements, while noting that other mechanisms could not be excluded. 
• B-cell recovery did not show a strong correlation with relapse or progression in this small cohort. 
• Persistent hypogammaglobulinemia was observed in the patient with sustained sCR, supporting continued monitoring of immunoglobulin levels and supportive therapy with intravenous immunoglobulin infusions.

Strengths  
• The report provides long-term follow-up of up to 15 months, extending the previously reported early safety and efficacy observations. 
• It documents subsequent treatments after relapse/progression and reports the feasibility of subsequent ex vivo CAR-T treatment in one patient.

Limitations  
• Small sample size of four patients. 
• Incomplete mechanistic understanding of early lymphocyte disappearance and relapse of extramedullary disease. 
• Many analyses were post hoc and require validation in prospective studies. 
• The authors state that larger cohorts with extended follow-up are needed.

Why this study matters 
In this four-patient follow-up study, in vivo BCMA-targeted ESO-T01 CAR-T therapy produced an objective response in all patients, with one patient maintaining sCR for 15 months and a median PFS of 4.0 months. Three patients subsequently developed extramedullary relapse or progression, and the study reported no new important ESO-T01-related safety signals during follow-up; the authors identified limited CAR-T persistence, small sample size, and incomplete understanding of relapse mechanisms as areas requiring further study.

Reference: 
Xu, J., Liu, L., Xie, W. et al. Extended follow-up of in vivo BCMA CAR-T therapy in relapsed/refractory multiple myeloma. Nat Med (2026). https://doi.org/10.1038/s41591-026-04704-z

MAIA frailty subgroup analysis: long-term follow-up with daratumumab plus lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma — Leukemia (October 2026)

What is the purpose of the study? 
To provide an updated analysis of the MAIA trial examining whether daratumumab plus lenalidomide/dexamethasone (D-Rd) continued to improve outcomes compared with lenalidomide/dexamethasone (Rd) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) according to frailty status.

Summary 
After a median follow-up of 64.5 months, D-Rd maintained improved progression-free survival (PFS) and higher rates of complete response (CR) or better and minimal residual disease (MRD) negativity (10⁻⁵) compared with Rd across frailty subgroups. Overall survival (OS) benefit was observed in the fit, intermediate, and total non-frail subgroups, while in the frail subgroup the OS hazard ratio favored D-Rd but was not statistically significant (HR 0.79; 95% CI, 0.58–1.06; P=0.1128). No new safety concerns were identified with longer follow-up, although grade 3/4 neutropenia and pneumonia were more frequent with D-Rd than Rd among frail patients, and lenalidomide and dexamethasone dose modifications or discontinuations were more common with D-Rd.

Key points 
• Population: Transplant-ineligible patients with newly diagnosed multiple myeloma enrolled in the MAIA trial. 
• Treatment comparison: D-Rd (daratumumab + lenalidomide + dexamethasone) versus Rd (lenalidomide + dexamethasone). 
• Frailty assessment: Retrospectively classified patients as fit, intermediate, non-frail (fit + intermediate), or frail using age, Charlson Comorbidity Index (CCI), and baseline Eastern Cooperative Oncology Group (ECOG) performance status. 
• Follow-up: Median 64.5 months, representing more than 5 years of follow-up.

• PFS: The PFS benefit with D-Rd was maintained across frailty subgroups, with reductions in the risk of disease progression or death of: 
 - 43% in fit patients 
 - 57% in intermediate patients 
 - 52% in total non-frail patients 
 - 36% in frail patients

• OS: D-Rd was associated with reductions in the risk of death of 52% in fit, 48% in intermediate, and 47% in total non-frail patients. In frail patients, the OS hazard ratio favored D-Rd (HR 0.79; 95% CI, 0.58–1.06; P=0.1128). 
• Treatment response: D-Rd produced higher rates of ≥CR and MRD negativity (10⁻⁵) than Rd across frailty subgroups. 
• Safety: No new safety concerns were observed during extended follow-up. Among frail patients, grade 3/4 neutropenia and pneumonia occurred more frequently with D-Rd than Rd. 
• Treatment modifications: Lenalidomide and dexamethasone discontinuations and dose modifications were more frequent with D-Rd; lenalidomide relative dose intensity was also lower with D-Rd. 
• Treatment duration: Duration of therapy was consistently longer with D-Rd than Rd across frailty subgroups. 
• Patient-reported outcomes: Improvements from baseline in global health status, pain, physical functioning, and fatigue were sustained over 5 years in the overall population and frail subgroup.

Strengths 
The analysis included extended follow-up of more than 5 years, allowing assessment of longer-term PFS, OS, response, and safety outcomes.

Limitations 
• Frailty was assessed retrospectively using baseline characteristics because the MAIA trial began before the International Myeloma Working Group (IMWG) frailty scoring system was available. ADL and IADL measures were not collected, so the results may not be fully generalizable to IMWG-defined frailty subgroups.

• Frailty status was not reassessed longitudinally in this analysis, although subsequent analyses indicated that frailty can change over time.

Why this study matters 
With more than 5 years of follow-up, the MAIA subgroup analysis found that D-Rd maintained improved PFS and deeper responses compared with Rd across frailty subgroups in transplant-ineligible NDMM. OS favored D-Rd in most frailty subgroups, while the OS difference was less pronounced in frail patients; the analysis reported no new safety concerns, but its interpretation is limited by retrospective frailty assessment based on baseline characteristics and the absence of longitudinal frailty assessment.

Reference: 
Facon, T., Cook, G., Usmani, S.Z. et al. MAIA frailty subgroup analysis: long-term follow-up with daratumumab plus lenalidomide/dexamethasone in transplant-ineligible newly diagnosed myeloma. Leukemia (2026). https://doi.org/10.1038/s41375-026-03128-5

European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP)

CHMP Recommends Earlier-Line Use of Talvey (Talquetamab) Plus Daratumumab for Relapsed/Refractory Myeloma

On Friday, October 16, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) recommended extending the indication for Johnson & Johnson’s TALVEY® (talquetamab) in combination with daratumumab, with or without pomalidomide, to treat adults with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior line of therapy, stated Johnson & Johnson in a press release.

If approved by the European Commission, the combination would offer a GPRC5D-targeting bispecific antibody treatment option as early as the second line of therapy. Talquetamab is currently authorized in the European Union as a single-agent treatment for eligible patients who have received at least three prior therapies and meet additional treatment-history criteria.

The CHMP recommendation is based on results from the ongoing Phase 3 MonumenTAL-3 trial (NCT05455320), which demonstrated significant improvements in progression-free survival (PFS), response rates and overall survival (OS) with talquetamab-based combinations compared with daratumumab, pomalidomide and dexamethasone (DPd).

Clinical trial results 
At a median follow-up of 24.6 months, both talquetamab plus daratumumab (Tal-D) and talquetamab plus daratumumab and pomalidomide (Tal-DP) significantly improved PFS compared with DPd.

At 24 months: 
• Progression-free survival: 81.3% with Tal-DP and 77.6% with Tal-D. 
• Overall survival: 89.2% with Tal-DP, 87.9% with Tal-D and 83.0% with DPd. 
• Overall response rate: 88.2% with Tal-DP, 88.5% with Tal-D and 77.6% with DPd. 
• Complete response or better: 71.1% with Tal-DP, 68.9% with Tal-D and 34.5% with DPd. 
• Minimal residual disease (MRD)-negative complete response or better: 52.3% with Tal-DP, 46.3% with Tal-D and 15.9% with DPd.

The PFS hazard ratio was 0.28 for Tal-DP (95% confidence interval [CI], 0.20–0.40; p<0.0001) and 0.33 for Tal-D (95% CI, 0.24–0.46; p<0.0001). These results correspond to approximately 72% and 67% lower relative hazards of disease progression or death, respectively, compared with DPd during the study follow-up.

OS also improved significantly. The hazard ratio was 0.47 for Tal-DP (95% CI, 0.30–0.73; p=0.0006) and 0.51 for Tal-D (95% CI, 0.33–0.78; p=0.0015), corresponding to approximately 53% and 49% lower relative hazards of death, respectively, compared with DPd. These relative hazard reductions are not equivalent to absolute reductions in the probability of death.

The trial enrolled 864 patients, all of whom had previously received lenalidomide and a proteasome inhibitor and had undergone at least one prior line of therapy. Most participants were refractory to lenalidomide (85.1%) and to their most recent treatment regimen (93.4%).

Safety findings 
The overall safety profiles of the talquetamab combinations were consistent with the known safety profiles of the individual medicines. However, adverse events and infections were common across all three treatment groups.

Grade 3 or 4 treatment-emergent adverse events occurred in 94.9% of patients receiving Tal-DP, 74.8% receiving Tal-D and 91.5% receiving DPd.

Infections of any grade occurred in 87.3% of patients receiving Tal-DP, 84.3% receiving Tal-D and 83.0% receiving DPd. More severe infections, classified as grade 3 or 4, occurred in 37.7%, 29.2%, and 42.2% of patients, respectively.

Grade 5 adverse events, meaning fatal adverse events, occurred in 1.8% of patients receiving Tal-DP, 4.0% receiving Tal-D and 4.6% receiving DPd. Fatal adverse events attributed to infections accounted for 0.7%, 1.5%, and 1.8%, respectively.

Adverse events led to treatment discontinuation in 10.5% of patients in the Tal-DP group, 8.0% in the Tal-D group and 6.7% in the DPd group. At the data cutoff, 70.3%, 69.7%, and 47.3% of patients, respectively, remained on their assigned study treatment.

How the combination works 
Talquetamab is a bispecific T-cell-engaging antibody that binds to GPRC5D, a protein highly expressed on multiple myeloma cells, and CD3 on T cells. This enables it to direct T cells towards myeloma cells and promotes their destruction. GPRC5D is a distinct target from B-cell maturation antigen (BCMA), another target used in multiple myeloma treatment and is absent or expressed at low levels on normal B cells.

Daratumumab targets CD38, a protein expressed on multiple myeloma cells, and promotes their destruction through immune-mediated mechanisms. Combining talquetamab and daratumumab therefore targets myeloma through two distinct mechanisms. Pomalidomide, an immunomodulatory medicine, is included in the Tal-DP regimen but not in Tal-D.

Johnson & Johnson said the findings support evaluating talquetamab-based combinations earlier in the treatment pathway, including in patients whose disease has relapsed or become refractory after at least one prior line of therapy.

A Summary of Product Characteristics from the EMA is available online to provide a full list of adverse events and information on dosage and administration, contraindications, and other precautions when using Talvey (talquetamab).

“In line with the European Medicine Agency’s regulations for new medicines and those given conditional approval, talquetamab is subject to additional monitoring,” said Johnson & Johnson.

References: 
CHMP recommends approval of Johnson & Johnson’s TALVEY®▼ (talquetamab) plus daratumumab in earlier line treatment of relapsed/refractory multiple myeloma. Johnson & Johnson press release. October 16, 2026.

Talvey (talquetamab) Summary of Product Characteristics. European Medicines Agency.

European Commission (EC)

European Commission Approves Expanded Indication for Teclistamab Monotherapy as Treatment for Relapsed/Refractory Myeloma  

On Friday, October 23, the European Commission (EC) approved an expanded indication for TECVAYLI® (teclistamab) monotherapy for adults with relapsed/refractory multiple myeloma (RRMM) who have received at least one prior therapy, as announced by Johnson & Johnson in a press release.  

EC approval was based on Phase 3 MajesTEC-9 trial (NCT05572515) results, which showed a 71% reduction in the risk of disease progression or death, and a 40% reduction in the risk of death compared with standard of care: pomalidomide, bortezomib, and dexamethasone (PVd); or carfilzomib and dexamethasone (Kd).

Results from the Phase 3 MajesTEC-9 trial demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS) compared with standard-of-care regimens.

The approval introduces another treatment option in the second-line setting, following the EC’s August 2026 approval of teclistamab in combination with daratumumab.

Survival benefits and response rates 
In MajesTEC-9, teclistamab reduced the risk of disease progression or death by 71% compared with standard care (hazard ratio [HR], 0.29; 95% confidence interval [CI], 0.23–0.38; p<0.001). The risk of death was reduced by 40% (HR, 0.60; 95% CI, 0.43–0.83; p=0.002).

At 18 months, the PFS rate was 69.8% with teclistamab, compared with 26.9% with standard care. The 18-month OS rate was 79.2% versus 68.6%, respectively. Complete response or better (≥CR) was achieved by 65.9% of patients receiving teclistamab, compared with 16.8% of those receiving standard treatment (p<0.001).

The randomized Phase 3 study compared teclistamab monotherapy, a bispecific T-cell engager, with either pomalidomide, bortezomib and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd). Participants had received one to three previous lines of therapy, including lenalidomide and an anti-CD38 monoclonal antibody. PFS was the primary endpoint; secondary endpoints included OS, response rates, duration of response, safety and patient-reported outcomes.

Safety findings 
The safety profile of teclistamab was consistent with that established in previous studies, although severe adverse events and infections were more frequent with teclistamab than with standard treatment.

Adverse events of any grade occurred in 99.7% of patients receiving teclistamab and 97.9% receiving standard care. Grade 3 or 4 adverse events occurred in 84.9% and 76.3%, respectively, while Grade 5 adverse events occurred in 6.5% and 3.5%.

Grade 3 or 4 infections were reported in 41.6% of patients receiving teclistamab, compared with 29.0% receiving standard care. The reported rates of Grade 3 or higher infections decreased over time. Median treatment duration was 13.1 months with teclistamab and 7.0 months with standard treatment.

Updated dosing schedule 
The revised product information will replace the existing monotherapy indication and dosing instructions. It introduces monthly dosing from month seven onward, with eligible patients able to transition to monthly administration as early as month three. The change is intended to simplify treatment and potentially reduce the burden of more frequent dosing.

Mechanism of action and clinical context 
The latest decision further expands the potential use of teclistamab-based treatment at first relapse. However, the MajesTEC-9 safety findings, particularly the rates of severe adverse events and infections, remain important considerations when evaluating the treatment’s benefits and risks.

Teclistamab is subject to additional monitoring under European medicines regulations. Patients and healthcare professionals should consult the European Medicines Agency’s Summary of Product Characteristics for complete information on indications, dosing, contraindications, warnings and adverse reactions.

References:

European Commission approves Johnson & Johnson’s TECVAYLI®▼ (teclistamab) monotherapy for relapsed/refractory multiple myeloma, expanding treatment options from first relapse. Johnson & Johnson press release. October 23, 2026.

Touzeau C, Mina R, Quach H, Hungria V, Bhutani D, Chen W, Kumar S, Chaulagain C, Dimopoulos MA, Bahlis NJ, Maral S, van de Donk NWCJ, Schmidt Filho J, Saja K, Teipel R, Ando M, Roeloffzen W, Annibali O, Augustson B, Botta C, Delforge M, Bourgeois E, Buda G, Hus M, Perrot A, Preis M, Beksac M, Pour L, Farmer S, Nunes M, Oriol A, Melchardt T, Hu Y, Flogegård M, Wang D, Pei L, Wroblewski S, Ariës IM, Quijano Cardé NA, Perova T, de Jager T, Yeh TM, Vanquickelberghe V, Shah P, Chastain K, Kobos R, Carson R, Landgren O; MajesTEC-9 Trial Investigators. Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy. N Engl J Med. 2026 Jul 30;395(5):440-453. doi: 10.1056/NEJMoa2603870.  

Tecvayli Summary of Product Characteristics. European Medicines Agency. 

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