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

Scope and Methodology    
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from August-September 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 September 23, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.    
 

Clinical Updates 
 

Multiple Myeloma: 2026 Update on Diagnosis, Risk-Stratification and Management — American Journal of Hematology (August 2026) 
 

What is the purpose of the clinical update? 
To provide an updated overview of the diagnosis, risk stratification, and management of multiple myeloma and smoldering multiple myeloma (SMM). It summarizes current diagnostic criteria, treatment approaches, supportive care, and evidence from randomized trials, including newer therapies for newly diagnosed and relapsed disease. 
 
Summary 
Multiple myeloma is diagnosed when ≥10% clonal bone marrow plasma cells or a biopsy-proven plasmacytoma is present together with at least one myeloma-defining event (MDE), including CRAB features or specific biomarkers such as ≥60% clonal bone marrow plasma cells, a serum involved/uninvolved free light chain (FLC) ratio ≥100 under specified conditions, or >1 focal lesion on MRI. Current treatment is based on transplant eligibility and risk, with initial therapy generally incorporating an anti-CD38 monoclonal antibody (daratumumab or isatuximab), bortezomib, lenalidomide, and dexamethasone (VRd), followed by autologous stem cell transplantation (ASCT) when appropriate; treatment of relapsed disease includes CAR-T cell therapy, bispecific antibodies, triplet regimens, and belantamab mafodotin. 
 
For high-risk SMM, the AQUILA randomized trial found that 3 years of daratumumab delayed progression to active myeloma and improved overall survival compared with active monitoring: 5-year progression-free survival was 63.1% versus 40.8%, respectively, and 5-year overall survival was 93.0% versus 86.9% (hazard ratio, 0.52; 95% CI, 0.27–0.98). 
 
Key points 

Diagnosis 
• Requires ≥10% clonal bone marrow plasma cells or biopsy-proven plasmacytoma plus ≥1 MDE. 
• MDEs include CRAB features and biomarkers including ≥60% clonal bone marrow plasma cells, serum FLC ratio ≥100 with specified involved-FLC and urine M-protein requirements, or >1 focal MRI lesion. 
• Approximately 2% of patients have true non-secretory multiple myeloma without detectable M protein. 
• Low-dose whole-body CT or PET/CT is preferred for assessing bone disease; conventional skeletal survey is less sensitive. 

Risk Stratification 
• High-risk disease is defined by specified cytogenetic and molecular abnormalities, including del(17p), p53 mutation, bi-allelic del(1p), gain(1q) in combination with specified abnormalities, and selected translocations. 
• Survival is influenced by host characteristics, tumor burden, disease biology, and response to therapy. 
• The study explicitly notes limitations of current risk-stratification models in the setting of modern therapy and identifies a need for stratification based on individual genomic groups. 

Initial and Maintenance Therapy 
• Initial therapy generally uses an anti-CD38 monoclonal antibody plus VRd, followed by ASCT in eligible patients. 
• Selected standard-risk patients may delay transplantation until first relapse. 
• Frail patients who are not transplant candidates may receive an anti-CD38 antibody plus lenalidomide and dexamethasone or VRd. 
• Standard maintenance is lenalidomide plus daratumumab or isatuximab; bortezomib plus lenalidomide is an alternative for high-risk disease. 

Relapsed Multiple Myeloma 
• Treatment selection depends on timing of relapse, previous response, disease aggressiveness, and performance status. 
• Major treatment options include CAR-T cell therapy, bispecific antibodies, triplet regimens, and belantamab mafodotin. 
• In patients refractory to lenalidomide, the study states that pomalidomide-based regimens are preferred. 

Smoldering Multiple Myeloma 
• Current SMM includes patients with heterogeneous risks of progression. 
• High-risk SMM has an estimated 25% annual risk of progression during the first 2 years, compared with approximately 5% annually for low-risk SMM. 
• In the AQUILA randomized trial, daratumumab for 3 years produced 5-year progression-free survival of 63.1% versus 40.8% with active monitoring, representing a 51% risk reduction (p<0.001). 
• Five-year overall survival was 93.0% versus 86.9% (hazard ratio, 0.52; 95% CI, 0.27–0.98). 
• The study recommends daratumumab for newly diagnosed high-risk SMM and observation without therapy for other patients. 

Supportive Care 
• Zoledronic acid or pamidronate is recommended for all patients; denosumab is an alternative, particularly with significant renal dysfunction. 
• The study describes infection-prevention strategies including antiviral, antibacterial, Pneumocystis jirovecii, and immunoglobulin prophylaxis in specified treatment settings. 

Limitations  
• Current survival estimates may underestimate present-day survival, because much of the underlying data predates newer immunotherapeutic agents. 
• Current risk-stratification models have limitations in the context of modern therapy. 
• Earlier SMM studies were explicitly described as limited by lack of power, safe and effective drugs, and a risk-adapted strategy. 
• Some evidence for lenalidomide-containing regimens in relapsed disease came mainly from populations not previously exposed to lenalidomide, whereas current practice often includes patients receiving lenalidomide maintenance. 
 
Why this clinical update matters 
This updated overview describes contemporary diagnostic criteria and treatment strategies for multiple myeloma, emphasizing risk stratification, transplant eligibility, maintenance therapy, and newer treatments for relapsed disease. For high-risk SMM, the AQUILA trial reported 5-year progression-free survival of 63.1% versus 40.8% and 5-year overall survival of 93.0% versus 86.9% with 3 years of daratumumab compared with active monitoring; the study recommends daratumumab for newly diagnosed high-risk SMM. 
 
Reference: 
S. V. Rajkumar, “Multiple Myeloma: 2026 Update on Diagnosis, Risk-Stratification and Management,” American Journal of Hematology (2026): 1–24, https://doi.org/10.1002/ajh.70475. 

Consensus Guidelines & Recommendations 
 

BRIDGE-2M: Optimizing Bridging Therapy Prior to CAR-T Therapy in Multiple Myeloma: A Modified Double-Blind Delphi Panel of US Physicians — Advances in Therapy (August 2026) 

What is the purpose of the consensus study? 
To reach expert consensus on how to select optimal bridging therapy (BT) for patients with relapsed/refractory multiple myeloma (RRMM) undergoing chimeric antigen receptor T-cell (CAR-T) therapy. It seeks to link patient-specific characteristics with clinical objectives for BT selection. 
 
Summary 
A double-blind, three-round modified Delphi study involving 15 U.S.-based hematologist-oncologists/hematologists with experience managing RRMM and using CAR-T therapy identified consensus factors influencing BT selection, including disease burden, disease aggressiveness, performance status, comorbidities, line of therapy, age, and frailty. Five patient-attribute/clinical-objective pairings reached consensus: age ≥65 years or frailty—disease stabilization (71%), poor performance status—end-organ function preservation (100%), comorbidities—functional preservation (100%), high disease burden—prevention of clinical decline (100%), and aggressive disease—cytoreduction (100%). 
 
The panel agreed that BT should aim to decrease disease burden and promote CAR-T efficacy and safety (100% consensus). Talquetamab was preferred by 66.7% of panelists for bridging in later lines of therapy, while 73.3% indicated they would consider earlier-line use if talquetamab were approved for that setting. Consensus was not reached that all patients should receive BT, particularly in the setting of low disease burden or indolent progression. 
 
Key points 
• Study design: Double-blind, anonymous, three-round modified Delphi panel conducted in the U.S. 
• Participants: 15 hematologist-oncologists/hematologists; all had managed approximately 60–100 patients with RRMM during the preceding year, and 86.7% had >5 years of practice experience. 
• Factors influencing BT selection: Disease burden, aggressive disease, performance status, comorbidities, line of therapy, age, and frailty. 
• Consensus patient attributes and clinical objectives: 
 - Age ≥65 years or frailty → disease stabilization: 71% consensus. 
 - Poor performance status → end-organ function preservation: 100% consensus. 
 - Comorbidities → functional preservation: 100% consensus. 
 - High disease burden → prevention of clinical decline: 100% consensus. 
 - Aggressive disease → cytoreduction: 100% consensus. 

• Overall BT goals: Decrease disease burden and promote CAR-T efficacy and safety (100% consensus). 
• Talquetamab: Preferred by 66.7% of panelists for bridging in later lines of therapy; 73.3% indicated they would consider earlier-line use if approved. 
• Treatment timing: Panelists aligned on using 1–2 cycles of BT, with 1–4 weeks of washout before CAR-T infusion. 
• BT was not considered mandatory for all patients: The statement that all patients should receive BT regardless of disease status did not reach consensus. 
• Earlier-line CAR-T: Panelists did not reach consensus on linking earlier-line CAR-T therapy with reducing clonal complexity because of uncertainty and the need for additional validation. 
 
Strengths  
• Double-blind, iterative, anonymous design intended to mitigate biases related to panelist identity, reputation, or fear of judgment 
• Moderated consensus-building in Round 3 allowed panelists to contribute on an equal basis in a controlled setting 
• All 15 panelists were unblinded after the study and agreed with the reported Round 3 findings 
 
Limitations  
• The panel was moderate in size and composed primarily of academic experts experienced with CAR-T, which may limit representation of community clinicians and settings with different access to therapy and healthcare resources. 
• Only 10 of the original 15 panelists participated in the final consensus meeting, so some final consensus classifications were based on a small denominator. 
• Borderline consensus statements were sensitive to panel composition, and the absence of five panelists may have influenced their final classification. 
• The Round 1 survey relied largely on open-text responses, limiting assessment of alignment on specific concepts. 
• As a Delphi study, the findings represent convergence of expert opinion based on clinical practice at the time of participation, rather than empirical clinical evidence. 
• The individualized and multifactorial nature of BT prescribing limited formal consensus for some individual attributes and treatment-preference statements. 
• The authors state that the results should be interpreted alongside emerging data in the evolving RRMM treatment landscape. 
 
Why this study matters 
This study developed an expert consensus-based framework linking five patient characteristics with specific clinical objectives for BT selection before CAR-T therapy in RRMM. The panel reached consensus that BT should decrease disease burden and promote CAR-T efficacy and safety, but did not reach consensus that BT should be given to every patient regardless of disease status; 66.7% of panelists preferred talquetamab for bridging in later lines of therapy, and 73.3% would consider earlier-line use if it were approved for that setting. 
 
Reference: 
Banerjee, R., Hashmi, H., Chaudhary, P.M. et al. BRIDGE-2M: Optimizing Bridging Therapy Prior to CAR-T Therapy in Multiple Myeloma: A Modified Double-Blind Delphi Panel of US Physicians. Adv Ther (2026). https://doi.org/10.1007/s12325-026-03737-7 

IFM 2026 Recommendations for First-Line Treatment of Newly Diagnosed Multiple Myeloma — Clinical Lymphoma Myeloma and Leukemia (September 2026) 
 

What is the purpose of the recommendations? 
To provide unified, evidence-based first-line treatment recommendations from the Intergroupe Francophone du Myélome (IFM) for patients with newly diagnosed multiple myeloma (NDMM), covering both transplant-eligible and transplant-ineligible patients. It also evaluates the role of measurable residual disease (MRD), next-generation sequencing (NGS), and emerging T-cell–redirecting therapies in the evolving first-line treatment landscape. 
 
Summary 
The IFM Treatment Guidelines Working Group developed these recommendations through a comprehensive literature review and expert consensus, addressing transplant-eligible and transplant-ineligible NDMM separately within a common framework. For transplant-eligible patients, daratumumab-VRd and isatuximab-VRd, supported by the PERSEUS and GMMG-HD7 trials, are recommended as reference induction regimens followed by autologous stem cell transplantation (ASCT), optional consolidation, and daratumumab-lenalidomide maintenance; for transplant-ineligible patients, daratumumab-lenalidomide-dexamethasone (DRd) remains the treatment backbone, with bortezomib-containing regimens considered for fit patients and daratumumab-lenalidomide (DR) without dexamethasone for frail patients. Mathematical modeling projected median progression-free survival (PFS) of approximately 205 months with daratumumab-VRd in transplant-eligible patients and approximately 100 months in transplant-ineligible/transplant-deferred patients. 
 
Key points 

• Treatment setting 
 - The recommendations cover both transplant-eligible (TE) and transplant-ineligible (TNE) patients with NDMM. 
 - Anti-CD38–based quadruplet regimens have increasingly replaced older triplet regimens as first-line standards. 
    
• Transplant-eligible patients 
 - Daratumumab-VRd and isatuximab-VRd are identified as reference induction regimens. 
 - Evidence cited includes the PERSEUS and GMMG-HD7 trials. 
 - The treatment sequence includes ASCT, optional consolidation, and daratumumab-lenalidomide maintenance. 
    
• Transplant-ineligible patients 
 - DRd, supported by the MAIA trial, remains the treatment backbone. 
 - In fit patients, adding bortezomib through isatuximab-VRd or daratumumab-VRd is discussed based on evidence from IMROZ, CEPHEUS, and BENEFIT. 
 - Frail patients receive DR without dexamethasone, based on IFM2017-03. 
    
• MRD and disease assessment 
 - MRD negativity, particularly when assessed by NGS at a sensitivity threshold of 10⁻⁵, or by NGF when NGS is not applicable, is described as an important treatment-response measure. 
 - The review discusses MRD and NGS-based high-risk myeloma definition across both transplant-eligible and transplant-ineligible populations. 
    
• Modeling 
 - Mathematical models projected median PFS of approximately 205 months with daratumumab-VRd in transplant-eligible patients (PERSEUS model) and approximately 100 months in transplant-ineligible/transplant-deferred patients (CEPHEUS model). 
    
• Emerging treatments 
 - Ongoing trials are evaluating CAR-T cells and bispecific antibodies as replacements for, or additions to, ASCT and maintenance therapy. 
 
Strengths  
• The recommendations use a unified framework and common methodology for transplant-eligible and transplant-ineligible NDMM. 
• They incorporate a comprehensive literature review, international guidelines, iterative expert discussion, and broad consensus within the IFM group. 
 
Limitations  
• The article is a narrative, expert-consensus review, rather than a systematic review. 
• It was not conducted according to PRISMA 2020 reporting guidelines. 
 
Why these recommendations matter 
The IFM review recommends anti-CD38–based treatment strategies as the current first-line framework for NDMM, with treatment pathways differentiated according to transplant eligibility and patient fitness. It emphasizes deeper responses and MRD assessment while identifying ongoing trials of CAR-T cells and bispecific antibodies that may alter the first-line treatment approach in the future. 
 
Reference: 
Aurore Perrot, Salomon Manier, Cyrille Hulin, Hélène Demarquette, Arthur Bobin, Laurent Frenzel, Lionel Karlin, Olivier Decaux, Mohamad Mohty, Bertrand Arnulf, Jérôme Lambert, Jill Corre, Thierry Facon, Philippe Moreau, Cyrille Touzeau, Xavier Leleu, IFM 2026 Recommendations for First-Line Treatment of Newly Diagnosed Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.09.002. 
 

Review 

Bispecific Antibodies and T-Cell Engagers in Multiple Myeloma — European Journal of Haematology (August 2026) 

What is the purpose of the review? 
To evaluate the structure, mechanisms of action, clinical data, practical use, sequencing, toxicities, and emerging resistance mechanisms of bispecific T-cell–redirecting antibodies in relapsed/refractory multiple myeloma (RRMM). It also examines their use relative to BCMA-directed CAR-T therapy and discusses emerging combinations and sequencing strategies. 
 
Summary 
The review describes four currently approved bispecific antibodies (teclistamab, elranatamab, linvoseltamab, and talquetamab) and summarizes clinical data for investigational agents targeting BCMA, GPRC5D, FcRH5, CD38, and other antigens. Across trials, these agents demonstrated clinical activity in heavily pretreated RRMM and, more recently, in earlier relapse; for example, the Phase 3 MajesTEC-3 (NCT05083169) trial reported longer progression-free survival (PFS) and overall survival (OS) with teclistamab plus daratumumab than investigator's-choice regimens. Important toxicities included cytokine release syndrome (CRS), infections, hypogammaglobulinemia, cytopenias, and immune effector cell-associated neurotoxicity syndrome (ICANS), while the review identifies unresolved questions regarding treatment duration, long-term immune effects, and sequencing with CAR-T therapy. 
 
Key points 

• Approved bispecific antibodies 
 - Teclistamab: In MajesTEC-1 (NCT03145181), ORR was 63.1%, with 39.4% achieving CR or better; median DOR was 18.4 months and median PFS 11.3 months. CRS occurred in 72.1%, neutropenia in 70.4%, and ICANS in 3%. 
 - Elranatamab: In MagnetisMM-3 (NCT04649359), ORR was 61% (75/123); among persistent responders switched to biweekly dosing, 80% (40/50) maintained responses for more than 6 months. Infections occurred in 69.9% and CRS in 57.7%. 
 - Linvoseltamab: In LINKER-MM1 (NCT03761108), updated results showed 76% ORR, 46% CR or better, and 62% VGPR or better; among CR-or-better, MRD-evaluable patients, 93% (25/27) were MRD-negative. CRS occurred in 46%, infections in 73%, and ICANS in 8%. 
 - Talquetamab: In MonumenTAL-1 (NCT03399799/NCT04634552), ORR was 74% with weekly dosing and 73% with biweekly dosing; among patients with prior T-cell–redirecting therapy, ORR was 63%. Common adverse effects include CRS, skin and nail changes, dysgeusia, and infections. 
    
• Earlier relapse 
 - In MajesTEC-3, 587 patients with 1–3 prior lines were randomized to teclistamab plus subcutaneous daratumumab or investigator's choice of DPd/DVd. 
 - At 34.5 months, median PFS was not reached versus 18.1 months; 36-month PFS was 83.4% vs. 29.7% (HR 0.17, 95% CI 0.12–0.23; p<0.0001). 
 - Three-year OS was 83.3% vs. 65.0% (HR 0.46, p<0.0001). 
 - MRD-negativity at 10⁻⁵ was 58.4% vs. 17.1%, and ORR was 89.0% vs. 75.3%. 
    
• Investigational bispecific antibodies 
 - Agents under development include cevostamab, etentamig (ABBV-383), Y150, EMB-06, forimtamig (RG6234), CS1-NKG2D bispecific antibody, and AFM26 CD16A-BCMA TandAb. 
 - Reported activity varies by agent, target, dose, and study population; some studies remain early-phase and have limited follow-up or incomplete human data. 
    
• Sequencing with CAR-T 
 - The review reports that bispecific antibodies targeting BCMA or other antigens can retain activity after CAR-T exposure, whereas outcomes with CAR-T after prior BCMA-directed therapy have generally been less favorable in the cited studies. 
 - Reported ORRs after prior CAR-T included 45% with teclistamab in a MajesTEC-1 cohort and 52.8% with elranatamab in pooled MagnetisMM analyses. 
 - In contrast, prior BCMA-directed therapy was associated with lower ORR and PFS with ide-cel in cited analyses. 
    
• Toxicities and management 
 - Infections and hypogammaglobulinemia are important adverse effects during prolonged bispecific therapy. Reported infection rates in pivotal studies ranged from approximately 57% to 76% for several monotherapy regimens. 
 - CRS is common, generally occurring early; step-up dosing and dose modification can reduce its frequency and severity. 
 - ICANS and cytopenias also occur and require monitoring and supportive management. 
 - GPRC5D-directed agents such as talquetamab have characteristic skin, nail, taste, and salivary-gland effects related to GPRC5D expression in keratin-producing tissues and salivary glands. 
 - The review states that IVIg supplementation reduces severe infections and recommends IVIg in patients with IgG <400 mg/dL or recurrent infections despite higher IgG levels. 
 
Strengths  
• The review incorporates data from randomized controlled trials, single-arm clinical trials, pooled analyses, and real-world studies across different disease settings. 
• It includes clinical data addressing both efficacy and toxicity, as well as treatment sequencing and emerging resistance mechanisms. 
 
Limitations/unresolved issues  
• Optimal treatment duration and fixed-duration or response-adapted discontinuation strategies have not been prospectively established. 
• The long-term immune consequences of prolonged T-cell engagement, including hypogammaglobulinemia, infection risk, and immune reconstitution, remain unresolved. 
• Optimal sequencing of bispecific antibodies and CAR-T therapy remains undefined. 
• The review notes that current sequencing evidence is dominated by single-arm and retrospective studies, and states that larger, longer-follow-up randomized comparisons are needed. 
 
Why this review matters 
The review reports that bispecific antibodies have demonstrated clinical activity across multiple settings of RRMM, including heavily pretreated disease, post-CAR-T relapse, and earlier relapse, with teclistamab plus daratumumab showing improved PFS and OS versus investigator's-choice regimens in MajesTEC-3. Their use is accompanied by clinically important risks including infections, hypogammaglobulinemia, CRS, cytopenias, and ICANS, while optimal treatment duration, long-term immune effects, and sequencing relative to CAR-T and other bispecific antibodies remain unresolved. 
 
Reference: 
M. Bhatt, S. V. Rajkumar, and S. Kumar, “Bispecific Antibodies and T-Cell Engagers in Multiple Myeloma,” European Journal of Haematology (2026): 1–14, https://doi.org/10.1111/ejh.70301. 
 

Research 
 

Patterns and perceptions of supplement use among patients with plasma cell disorders — Blood Cancer Journal (August 2026) 

What is the purpose of the study? 
To examine dietary supplement use among patients with plasma cell disorders (PCDs), including multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and smoldering multiple myeloma (SMM). It assesses changes in supplement use before and after diagnosis, patients’ perceptions and motivations, sources of information, interest in medical guidance and research, and areas for future investigation, with particular focus on vitamin D, curcumin/turmeric, omega-3, and probiotics. 
 
Summary 
Researchers conducted a 23-question online survey from September 2023 to May 2024 among registered HealthTree® Foundation Patient Portal users with a self-reported PCD diagnosis; 563 participants responded, representing an approximately 6.3% response rate. Supplement use increased after diagnosis, with 96% reporting use of at least one supplement compared with 72% before diagnosis (p<0.00001), and use of six or more supplements increasing from 12% to 34% (p<0.00001). After diagnosis, use of vitamin D, curcumin/turmeric, and probiotics increased significantly, whereas omega-3 use did not; 75% of respondents wanted supplement recommendations from their hematologist/oncologist and 91% wanted information about research on supplement risks and benefits. 
 
Key points 
• Participants: 563 respondents; 60% female, 59% aged ≥65 years, 79% White, 68% with at least a college degree, and 73% with MM. 
• Overall supplement use: Use of at least one supplement increased from 72% before PCD diagnosis to 96% after diagnosis (p<0.00001). 
• Number of supplements: Use of ≥6 supplements increased from 12% to 34% after diagnosis (p<0.00001). 
• Age: Participants aged ≤50 years were more likely than older participants to increase supplement use after diagnosis (p<0.005). 
• Specific supplements after vs before diagnosis: 
 - Vitamin D: 87% vs 47% (p<0.001) 
 - Curcumin/turmeric: 47% vs 19% (p<0.001) 
 - Probiotics: 47% vs 36% (p<0.001) 
 - Omega-3: 33% vs 34% (no significant difference) 

• Vitamin D monitoring: 67% reported that a doctor had checked their vitamin D level, but 65% were unsure of the result or did not remember being tested. 
• MGUS/SMM vs MM: Participants with MGUS/SMM reported higher use of omega-3 (46% vs 32%, p<0.05) and curcumin/turmeric (66% vs 42%, p<0.001); vitamin D and probiotic use did not differ significantly. 
• Reasons for supplement use after diagnosis: immune support (70%), prevention of nutritional deficiencies (53%), mitigating disease progression (39%), and improving chemotherapy tolerance (17%). 
• Information and guidance: Hematologists/oncologists and online medical resources were each reported by 46% as information sources. Overall, 58% followed advice from a physician, dietician, or nutritionist. 
• Interest in guidance/research: 75% wanted supplement recommendations from their hematologist/oncologist, and 91% wanted to learn about research on supplement risks and benefits in relation to their PCD. 
 
Limitations 
• The sample overrepresented White participants 
• Data were self-reported and subject to recall bias 
• Online recruitment may have introduced selection bias related to interest in supplements/complementary medicine and technological proficiency 
• Only four supplements were specifically assessed 
• Other supplement use, including multivitamins, was not systematically characterized; and potential drug interactions between supplements and cancer therapies were not evaluated. 
 
Why this study matters 
Supplement use was reported by 96% of respondents after PCD diagnosis, compared with 72% before diagnosis, with increases particularly reported for vitamin D, curcumin/turmeric, and probiotics. The study identified gaps in supplement monitoring and clinical guidance and found substantial patient interest in receiving recommendations from hematologists/oncologists and learning about research on supplement risks and benefits; the authors also noted that there are no established guidelines or current clinical studies directly addressing supplement benefits for PCDs, while the NUTRIVENTION trials (NCT05640843 and NCT06055894) are investigating certain supplements in precursor PCDs. 
 
Reference: 
Malik, M.A., Schach, E., Leyfman, Y. et al. Patterns and perceptions of supplement use among patients with plasma cell disorders. Blood Cancer J. 16, 137 (2026). https://doi.org/10.1038/s41408-026-01603-x 

Multiple myeloma and therapy reshape the bone marrow niche to durably constrain immune reconstitution and vaccine responsiveness — Cell Press Blue (August 2026) 

What is the purpose of the study? 
To characterize how multiple myeloma (MM) and its treatment affect immune function over time by longitudinally profiling matched bone marrow and peripheral blood from diagnosis through induction therapy, autologous stem cell transplant (ASCT), and recovery. It also examines immune reconstitution and responses to influenza and SARS-CoV-2 mRNA vaccination after ASCT. 
 
Summary 
Longitudinal multi-omic profiling showed that MM was associated with distinct, compartment-specific immune states in bone marrow and blood, including opposing metabolic and inflammatory signatures, while induction therapy selected persistent transcriptional states among residual myeloma plasma cells. Immune reconstitution remained impaired for up to 2 years after ASCT, with abnormalities in hematopoietic progenitors, B cells, T follicular helper (Tfh) cells, and cytotoxic immune subsets. Half of patients did not develop IgG responses to the high-dose, non-adjuvanted influenza vaccine, whereas all patients developed serologic responses after lipid nanoparticle (LNP)-adjuvanted SARS-CoV-2 mRNA vaccination. 
 
Key points 
• Tumor and treatment effects: Induction therapy was associated with selection of persistent malignant plasma-cell transcriptional states, including enrichment of the NDMM_5 state among residual tumor cells. 
• Bone marrow vs blood: Bone marrow and peripheral blood showed divergent inflammatory and metabolic transcriptional states during treatment and recovery. 
• Hematopoietic and immune recovery: Post-ASCT abnormalities included lineage-biased progenitor dynamics, persistent depletion and transcriptional abnormalities in early hematopoietic stem/progenitor and lymphoid progenitor states, reduced naive and memory B-cell and Tfh subsets, and sustained cytotoxic skewing. 
• Vaccine responses: Influenza vaccine responses were heterogeneous; 50% of patients failed to mount IgG responses to the high-dose, non-adjuvanted influenza vaccine. SARS-CoV-2 mRNA vaccination delivered in LNPs elicited serologic responses in all patients in the cohort. 
 
Strengths 
Paired bone marrow and blood sampling and use of orthogonal modalities strengthened assessment of compartment-specific signatures and therapy-related remodeling. 
 
Limitations 
The cohort was modest in size, with attrition at later time points, limiting some analyses. Increasing use of daratumumab-based regimens (DVRd) limited subgroup and clinical-association analyses. Pathway analyses were based on transcriptional signatures rather than direct functional measurements, and the study could not distinguish whether persistent marrow changes resulted from MM, treatment-related “scarring,” or ongoing maintenance therapy. Actual infection events were not recorded, and comparisons with external healthy controls for influenza were complicated by differences in vaccine formulation and timing after transplant. 
 
Why this study matters 
The study found that MM and its treatment were associated with prolonged, compartment-specific alterations in immune and hematopoietic states that persisted during post-ASCT recovery, including abnormalities extending beyond reduced blood-cell counts. Influenza vaccine responses were variable, while all patients in the cohort mounted serologic responses to LNP-adjuvanted SARS-CoV-2 mRNA vaccination; the authors state that prospective controlled studies are needed to establish whether adjuvanted or mRNA-based influenza vaccination strategies produce more consistent responses in post-ASCT patients with MM. 
 
Reference: 
Aishwarya Chander, Samir Rachid Zaim, Medbh A. Dillon, et al. Multiple myeloma and therapy reshape the bone marrow niche to durably constrain immune reconstitution and vaccine responsiveness, Cell Press Blue, 2026, 100087, ISSN 3051-3839, https://doi.org/10.1016/j.cpblue.2026.100087. 
 
 

Anti-BCMA immunotherapies deplete plasmacytoid dendritic cells and impair antiviral immunity in multiple myeloma — HemaSphere (August 2026) 

What is the purpose of the study? 
To investigate whether anti-B-cell maturation antigen (BCMA) immunotherapies, including bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR)-T cells, deplete plasmacytoid dendritic cells (pDCs) and thereby affect antiviral immune responses in patients with multiple myeloma (MM). It specifically examines BCMA expression in pDCs, changes in pDC populations during treatment, and interferon-α (IFN-α) production after viral-like stimulation. 
 
Summary 
The study analyzed 388 unique samples from 72 patients with MM, including 373 samples from 57 patients receiving teclistamab (tec), elranatamab (elra), talquetamab (tal), or ciltacabtagene autoleucel (cilta-cel), together with publicly available single-cell RNA sequencing datasets and bone marrow samples. BCMA mRNA and surface protein were detectable in pDCs, while GPRC5D expression in pDCs was negligible; anti-BCMA therapy was associated with rapid pDC depletion in peripheral blood and bone marrow, whereas pDCs remained detectable during anti-GPRC5D therapy. In an in vitro assay, CpG-A stimulation produced IFN-α in samples from patients receiving tal but not tec (P = 0.016), while IFN-γ and TNF-α did not differ between groups. 
 
Key points 

• Study population and methods 
 - 72 MM patients contributed 388 unique samples across multiple cohorts. 
 - Immunomonitoring included patients treated with: 
    • Teclistamab (tec): 15 patients, 114 samples 
    • Elranatamab (elra): 10 patients, 53 samples 
    • Talquetamab (tal): 19 patients, 100 samples 
    • Ciltacabtagene autoleucel (cilta-cel): 13 patients, 106 samples 
 - BCMA expression was assessed using publicly available scRNA-seq datasets from 13 healthy-donor bone marrow samples and by spectral cytometry in 15 newly diagnosed MM patients. 
 - Peripheral blood was assessed longitudinally from day 0 through day 360; paired bone marrow samples were evaluated at baseline and during minimal residual disease (MRD) assessment. 
    
• BCMA expression in pDCs 
 - Both scRNA-seq datasets showed detectable BCMA expression in pDCs, at levels comparable to those in B cells. 
 - Surface BCMA was also detected on pDCs in bone marrow samples. 
 - The proportion of BCMA-positive cells was significantly higher in pDCs than in pro-B, immature B, and mature B cells (all P < 0.001) and was similar to that of pre-B cells. 
 - GPRC5D expression was negligible in pDCs and mDCs. 
    
• Effect of anti-BCMA therapy on pDCs 
 - In patients receiving anti-BCMA bsAbs, pDCs declined rapidly by day 7 (P = 0.011) and were completely depleted by day 14 (P < 0.001). 
 - pDC depletion persisted through day 360 (P < 0.001–0.008). 
 - Similar findings were observed separately with teclistamab and elranatamab. 
 - In contrast, pDCs remained detectable throughout talquetamab treatment. 
 - CD1c-positive myeloid/conventional dendritic cells (mDCs) were not reduced between the BCMA- and GPRC5D-targeted groups. 
    
• Effect of cilta-cel 
 - After cilta-cel, pDCs decreased by day 7 (P = 0.039) and were absent at days 14, 21, and 30. 
 - pDC recovery was observed from day 60 (P = 0.009) and was more evident at day 90 compared with day 30 (P = 0.001). 
 - B-cell kinetics followed a similar pattern, while mDCs were not depleted. 
    
• Bone marrow findings 
 - During MRD evaluation, pDCs were absent in the anti-BCMA group compared with the GPRC5D group (P = 0.037). 
 - B cells were also depleted in the anti-BCMA group (P = 0.012). 
 - mDCs remained detectable in all analyzed samples. 
    
• Antiviral functional assay 
 - Following stimulation with the TLR9 agonist CpG-A, IFN-α production was robust in samples from patients receiving tal but absent in samples from patients receiving tec (P = 0.016). 
 - IFN-α was undetectable without stimulation in both groups. 
 - IFN-γ and TNF-α did not differ between treatment groups or stimulation conditions. 
 
Strengths  
• The investigation used multiple complementary approaches, including publicly available scRNA-seq data, spectral cytometry, longitudinal peripheral-blood sampling, paired bone marrow analysis, and an in vitro functional assay. 
• It evaluated both anti-BCMA and anti-GPRC5D therapies, as well as BCMA-directed CAR-T therapy, allowing comparison across treatment modalities. 
 
Why this study matters 
The study found that pDCs express BCMA and are depleted in patients receiving anti-BCMA bsAbs or cilta-cel, while mDCs were not similarly depleted and pDCs remained detectable during anti-GPRC5D therapy. Patients receiving teclistamab had absent IFN-α production after CpG-A stimulation compared with patients receiving talquetamab, supporting an association between BCMA-targeted therapy, pDC depletion, and reduced IFN-α responses. 
 
 
Reference: 
Venglar, O., Radova, E., Warmuzova, M., Bilek, D., Kudelkova, M., Jasinkova, K., Muronova, L., Broskevicova, L., Kapustova, V., Vrana, J., Novakova, T., Karasova, K., Hornakova, M., Popkova, T., Mihalyova, J., Plonkova, H., Simicek, M., Radocha, J., Sevcikova, T., Zihala, D., Bago, J., Hajek, R. and Jelinek, T. (2026), Anti-BCMA immunotherapies deplete plasmacytoid dendritic cells and impair antiviral immunity in multiple myeloma. HemaSphere, 10: e70455. https://doi.org/10.1002/hem3.70455 

Salvage treatment patterns in multiple myeloma patients progressing after lenalidomide maintenance: A real-life study from European Myeloma Network (EMN) Italy — British Journal of Haematology (August 2026) 

What is the purpose of the study? 
To evaluate the effectiveness of treatment regimens licensed in Italy for patients with multiple myeloma (MM) who were refractory to lenalidomide (Len-R) and experienced their first relapse during Len maintenance after autologous haematopoietic stem cell transplantation (AHSCT). It also assesses clinical and biological factors associated with progression-free survival (PFS) and overall survival (OS). 
 
Summary 
The retrospective and prospective cohort PALLADIO study included 306 Len-R patients treated at first relapse after AHSCT and Len maintenance across 31 Italian centres. The most frequently used regimens were isatuximab–carfilzomib–dexamethasone (Isa-KD; 45.4%), daratumumab–pomalidomide–dexamethasone (D-PD; 19.3%), and daratumumab–bortezomib–dexamethasone (D-VD; 12.4%). Anti-CD38 monoclonal antibody (anti-CD38 MoAb)-based regimens were associated with improved survival compared with anti-CD38-sparing regimens, with Isa-KD having the longest median PFS at 22.8 months; high LDH, ISS ≥2, and relapse within 12 months of starting maintenance were associated with shorter PFS and OS. 
 
Key points 
• Population: 306 patients with Len-R MM who had received AHSCT, Len maintenance, and treatment at first relapse. 
• Most-used treatments: 
 - Isa-KD: 45.4% 
 - D-PD: 19.3% 
 - D-VD: 12.4% 

• Median PFS: 
 - Isa-KD: 22.8 months 
 - D-PD: 17.29 months 
 - D-VD: 20.12 months 
    
• Anti-CD38 findings: Anti-CD38 MoAb-based regimens, particularly proteasome inhibitor (PI) + anti-CD38 MoAb combinations, were associated with a significant PFS benefit and an OS advantage compared with anti-CD38-sparing combinations. Isa-KD had the longest median PFS (22.8 months). 
    
• High-risk features associated with shorter PFS and OS: 
 - High LDH at relapse: PFS p = 0.0003; OS p < 0.0001 
 - ISS ≥2 at relapse: PFS and OS p < 0.0001 
 - Early relapse (<12 months) after starting maintenance: PFS p = 0.0017; OS p = 0.0009 
 
Limitations 
• Substantial imbalance in sample sizes between treatment groups. 
• Differences in patient accrual timing and follow-up duration, creating challenges for direct treatment comparisons. 
• The efficacy of Isa-KD may have been underestimated because its subgroup may have been enriched for patients with early, aggressive relapses. 
 
Why this study matters 
In this homogeneous cohort of Len-R MM patients treated at first relapse after Len maintenance, anti-CD38 MoAb-based combinations, particularly PI + anti-CD38 MoAb combinations, were associated with longer PFS and an OS advantage compared with anti-CD38-sparing combinations, with Isa-KD showing the longest median PFS at 22.8 months. Patients with high-risk disease features, including high LDH, ISS ≥2, or relapse within 12 months of maintenance initiation, had poorer outcomes; the authors also describe the introduction of BCMA-directed therapies, including CAR-T cells and bispecific antibodies, as providing additional treatment options for this population. 
 
Reference: 
Barilà G, Grassi A, Ruocco V, Liberatore C, Olivari E, Tinelli M, et al. Salvage treatment patterns in multiple myeloma patients progressing after lenalidomide maintenance: A real-life study from European Myeloma Network (EMN) Italy. Br J Haematol. 2026; 00: 1–11. https://doi.org/10.1111/bjh.70751 
 
 

Lesion-level PET/CT analysis to identify predictors of progression after BCMA CAR T-cell therapy in multiple myeloma — Blood Cancer Journal (August 2026) 
 

What is the purpose of the study? 
To characterize patterns of relapse after BCMA-directed CAR T-cell therapy with ciltacabtagene autoleucel (cilta-cel) in relapsed/refractory multiple myeloma (RRMM) using longitudinal 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). It specifically evaluates patient-level and individual-lesion characteristics associated with progression, with emphasis on extramedullary disease (EMD) and paramedullary disease (PMD). 
 
Summary 
This retrospective study evaluated 102 triple-class-exposed RRMM patients treated with cilta-cel at Memorial Sloan Kettering Cancer Center from 2018–2024, using FDG PET/CT before apheresis, before lymphodepleting chemotherapy (LDC), at day 30 after infusion, and at first progression. After a median follow-up of 19 months, 40 patients progressed; 90% had a radiologic component to progression, and disease distribution shifted from 38% EMD/PMD at baseline to 72% at progression. Pre-LDC lesion number and EM/PM involvement were associated with inferior progression-free survival (PFS) and overall survival (OS), while at the lesion level, EM/PM lesions progressed more frequently than bone lesions and lesions with a complete metabolic response at day 30 rarely progressed. 
 
Key points 
• Study population: 102 triple-class-exposed RRMM patients treated with cilta-cel; median 5 prior lines of therapy; 38% had EMD/PMD at apheresis. 
• Progression: At a median follow-up of 19 months, 40/102 patients progressed; 90% (36/40) had radiologic progression, including 28% with radiologic-only progression. 
• Anatomic distribution: Bone-only disease decreased from 62% at baseline to 28% at progression, while combined EMD/PMD increased from 38% to 72%. 
• Pre-LDC lesion burden: 24-month PFS was 75%, 42%, and 22% for patients with 0, 1–3, and ≥4 lesions, respectively (p<0.001). For ≥4 lesions, 24-month OS was 60%, compared with 89% for 0 lesions and 74% for 1–3 lesions (p=0.018). 
• Pre-LDC disease location: EM/PM disease was associated with 24-month PFS of 5.5% versus 66% for bone-only or no PET-avid radiologic disease (p<0.001) and 24-month OS of 47% versus 88% (p<0.001). 
• Multivariable analysis: Pre-LDC PMD (HR 20.4; 95% CI 7.2–58) and EMD (HR 7.1; 95% CI 2.9–17) were independently associated with inferior PFS; PMD (HR 5.4) and EMD (HR 3.9) remained independently prognostic for OS. 
• Lesion-level findings: EM and PM lesions had higher baseline median SUV than bone lesions (6.4 and 7.4 vs 4.6; p=0.008) and progressed at first POD in 41% of EM, 31% of PM, and 11% of bone lesions (p<0.001). 
• Day 30 metabolic response: Lesions in complete response (CR) progressed at first POD in 2.1%, compared with 27% of partial-response (PR) and 40% of stable-disease (SD) lesions (p=0.006). EM/PM lesions with incomplete day-30 response progressed at approximately 50%, compared with 20% of bone lesions. 

Strengths
The study provides patient- and individual-lesion-level longitudinal FDG PET/CT analysis of relapse after BCMA CAR T-cell therapy; it also incorporated serial imaging across multiple treatment timepoints. 

Limitations
Retrospective design; limited number of events and follow-up; non-protocolized imaging; lesion-level response thresholds were not prospectively defined; small subgroups limited some estimates; and heterogeneity in bridging therapy may have influenced pre-infusion disease.

Why this study matters 
In this cohort of RRMM patients treated with cilta-cel, progression was predominantly associated with radiologic disease and became increasingly concentrated in EM/PM sites. Pre-LDC lesion burden and EM/PM involvement, as well as persistent metabolic activity at day 30, were associated with progression at the patient or lesion level; the study states that whether treatment escalation based on these findings improves outcomes requires prospective evaluation. 
 
Reference: 
Dreyfuss, A.D., Yahalom, J., Rajeeve, S. et al. Lesion-level PET/CT analysis to identify predictors of progression after BCMA CAR T-cell therapy in multiple myeloma. Blood Cancer J. 16, 139 (2026). https://doi.org/10.1038/s41408-026-01607-7 
 
 

The cumulative effect of cytogenetic abnormalities on the outcomes of myeloma patients with del(17p) undergoing AHSCT in EBMT centres between 2016 and 2022 — British Journal of Haematology (August 2026) 
 

What is the purpose of the registry study? 
To evaluate real-world post-autologous hematopoietic stem cell transplantation (AHSCT) outcomes in almost 2,500 patients with multiple myeloma (MM) and deletion 17p [del(17p)]. It examines progression-free survival (PFS) and overall survival (OS), including the association of additional high-risk cytogenetic abnormalities (HRCA) and pre-AHSCT disease response with outcomes. 
 
Summary 
In the contemporary EBMT cohort (2016–2022), PFS and OS rates were 77% and 90% at 1 year and 46% and 68% at 3 years, respectively. Concurrent del(17p) and t(4;14) was associated with poorer outcomes, while a pre-AHSCT disease response of ≤ partial response (PR) was associated with poorer OS. The study reports that del(17p) remained associated with poorer outcomes in the modern treatment era and that the presence of additional HRCA had a compounding adverse effect. 
 
Key points 

• Study population: Almost 2,500 AHSCT-eligible patients with MM and del(17p) in a contemporary EBMT registry cohort. 
• Survival outcomes (2016–2022): 
 - 1-year PFS: 77% 
 - 1-year OS: 90% 
 - 3-year PFS: 46% 
 - 3-year OS: 68% 

• Concurrent high-risk abnormalities: Patients with del(17p) and t(4;14) had poorer outcomes; the study identifies this group as having two high-risk cytogenetic abnormalities and describes it as an ultra-high-risk cohort. 
• Response before AHSCT: A disease response of ≤PR before AHSCT was associated with poorer OS. 
• IFM-2009 comparison: For comparison, OS in the IFM-2009 trial transplant arm (lenalidomide, bortezomib, dexamethasone + AHSCT) was 81% at 4 years. 
• Effect of additional HRCA: The study reports that the adverse effect of HRCA can accumulate. In a systematic review of 24 randomized controlled trials involving 13,926 patients, the HR for PFS was 2.28 (95% CI, 2.05–2.54) for patients with ≥2 HRCA and 1.51 (95% CI, 1.38–1.65) for patients with 1 HRCA; the corresponding HRs for OS were 2.94 (95% CI, 2.49–3.47) and 1.69 (95% CI, 1.52–1.88). 
 
Strengths
The authors describe the analysis as one of the largest registry analyses to date of real-world post-AHSCT outcomes in patients with del(17p) MM. 
 
Limitations 
Testing for del(1p) and gain(1q) was not recommended as standard of care between 2016 and 2022. Therefore, it remains unclear how many patients classified as having del(17p) as their only HRCA may have had additional adverse cytogenetic abnormalities. The authors state that this lack of testing limits the additional insight the cohort can provide for patient care going forward. 
 
Why this study matters 
This large registry study found that AHSCT-eligible patients with MM and del(17p) continued to have poorer outcomes with standard approaches to therapy. Patients with del(17p) and t(4;14), representing two high-risk cytogenetic abnormalities, constituted an ultra-high-risk cohort, and a pre-AHSCT response of ≤PR was associated with poorer OS; the authors also note that limited testing for del(1p) and gain(1q) restricts interpretation of the number of additional adverse cytogenetic abnormalities present. 
 
 
Reference: 
Comerford, C., Hayden, P.J., Eikema, D.-J., Koster, L., Sauer, S., Broers, A., Rabin, N., Bastie, J.N., Gedde-Dahl, T., Giaccone, L., Richardson, D., Carlson, K., Besemer, B., de Colella, J.-M.S., Zeiser, R., Vincent, L., Pabst, T., Cairoli, A., Schuermans, C., Poiani, M., Raj, K., Drozd-Sokolowska, J., Garderet, L., Najjar, I.E., Beksac, M. and McLornan, D.P. (2026), The cumulative effect of cytogenetic abnormalities on the outcomes of myeloma patients with del(17p) undergoing AHSCT in EBMT centres between 2016 and 2022. Br J Haematol. https://doi.org/10.1111/bjh.70759 

Persistence of M-proteins detected by mass spectrometry — Blood Cancer Journal (August 2026) 
 

What is the purpose of the study? 
To evaluate the persistence of monoclonal proteins (M-proteins) associated with monoclonal gammopathy of undetermined significance (MGUS) when detected by MALDI-TOF mass spectrometry (Mass-Fix), including low-level M-proteins that may not be measurable by serum protein electrophoresis (SPEP). It also examines clinical progression of MGUS after detection by Mass-Fix. 
 
Summary 
The study included 761 of 6035 verified MGUS patients who had at least 3 Mass-Fix tests over a minimum of 6 months without MGUS progression. Overall, 97% of Mass-Fix-detected M-proteins persisted for at least 6 months; persistence was 93% among M-proteins representing 1–10% of the total immunoglobulin of the corresponding heavy-chain isotype and 99.8% when the M-protein represented >10%. Clinical progression occurred across most isotype and M-protein-size groups, except among IgM M-proteins <50%, in which no clinical progression was observed. 
 
Key points 
• Study population: 761 patients with MGUS, selected from 6035 verified MGUS patients in a dysproteinemia database. 
• Patients had ≥3 Mass-Fix tests spanning ≥6 months and no MGUS progression during the testing period. 
• Persistence: 97% of Mass-Fix-detected M-proteins persisted for at least 6 months. 
• For M-proteins >50% of the total corresponding heavy-chain isotype, persistence was observed in 100% of cases. 
• For low-level M-proteins representing 1–10%, persistence was 93%. 
• When the M-protein represented >10% of the total immunoglobulin of its heavy-chain isotype, 99.8% persisted. 
• The lowest persistence was observed among low-level IgM M-proteins. 
• The percentage of M-protein relative to the polyclonal background increased over time on average. 
• Clinical progressions were observed in all isotype and M-protein-size groups except IgM M-proteins <50%. 
• Compared with a previous study of low-level M-proteins detected by IFE, persistence was 93% with Mass-Fix versus 70% with IFE; the study also references a reported 99.6% persistence with SPEP. 
• The authors note that low-level IgM M-proteins showed no clinical progression in both the current Mass-Fix study and the prior IFE study. 
• The study states that the clinical significance of detecting MGUS earlier with Mass-Fix remains uncertain, and screening asymptomatic patients for M-proteins by any method is not recommended. 
• The authors note that further studies are needed to determine whether the increased progression risk associated with non-IgG M-proteins also applies to low-level M-proteins. 
 
Limitations  
• The study was not population-based and did not use systematic patient sampling; therefore, it cannot be used to determine prevalence, progression rates, or absolute rates of persistent proteins. 
• Because the quantitative version of Mass-Fix was only clinically available beginning in early 2024, M-protein quantitation in this study was relatively quantitative and used the percentage of the relevant heavy-chain isotype spectrum as a surrogate for M-protein size. 
• The authors state that future studies could use the quantitative Mass-Fix assay, which has an analytical measuring range of 10–0.01 g/dL, once longer-term data are available. 
• The authors also note that their Mass-Fix data may overestimate persistence of small IgM M-proteins because low-level IgM M-proteins were not routinely reported. 
 
Why this study matters 
In this study, most low-level M-proteins detected by Mass-Fix persisted for at least 6 months, including 93% of M-proteins representing 1–10% of the corresponding immunoglobulin isotype. The authors conclude that these findings are consistent with low-level Mass-Fix-detected M-proteins being MGUS-related, while noting that the clinical utility of detecting very low-level M-proteins earlier remains uncertain and that further studies are needed, particularly for low-level non-IgG M-proteins. 
 
Reference: 
Murray, D.L., Coker, J., Kourelis, T. et al. Persistence of M-proteins detected by mass spectrometry. Blood Cancer J. 16, 140 (2026). https://doi.org/10.1038/s41408-026-01610-y 
 
 

Engineering a TACI × CD3 bispecific antibody to redirect T cells against multiple myeloma — Blood Advances (August 2026) 
 

What is the purpose of the study? 
To develop and evaluate a T-cell–redirecting bispecific antibody (bsAb) targeting transmembrane activator and CAML interactor (TACI) and CD3 as an alternative approach for treating multiple myeloma (MM), particularly when B-cell maturation antigen (BCMA) expression is reduced or lost. The investigators assess whether TACI × CD3 bsAb could activate T cells and kill MM cells, including cells resistant to BCMA-targeted treatment. 
 
Summary 
The TACI × CD3 bsAb induced T-cell activation, proliferation, cytokine production, and cytotoxicity against MM cells in vitro, in vivo, and in primary MM samples from patients. It retained activity against BCMA-knockdown (BCMA^KD) MM cells that were unresponsive to BCMA × CD3 bsAb treatment, although its tumor-suppressive effect in the MM xenograft model was somewhat lower against BCMA^KD than BCMA-wild-type (BCMA^WT) cells. The bsAb also induced cytotoxicity against primary MM cells and promoted CD8+ T-cell activation in patient-derived bone marrow samples, with responses varying among specimens. 
 
Key points 
• Target: TACI × CD3 bispecific antibody, designed to redirect T cells toward MM cells. 
• Rationale: Loss or downregulation of BCMA is a major mechanism associated with relapse and resistance after BCMA-directed therapies. 
• Antitumor activity: TACI × CD3 bsAb produced T-cell activation, proliferation, cytokine production, and cytotoxicity against MM cells. 
• BCMA-low/knockdown cells: The bsAb remained effective against BCMA^KD MM cells, including cells that did not respond to BCMA × CD3 bsAb treatment. 
• In vivo findings: In an MM xenograft model, TACI × CD3 bsAb significantly suppressed tumor growth, but its efficacy was somewhat reduced against BCMA^KD compared with BCMA^WT MM cells. 
• Primary patient samples: The bsAb induced cytotoxicity against primary MM cells and promoted CD8+ T-cell activation in patient-derived bone marrow samples. 
• Variation in responses: Responses in patient-derived specimens varied; the study attributes this likely to interpatient heterogeneity and differences in the number and functional state of recovered T cells after thawing. 
• TACI expression: The study reports that TACI expression is independent of BCMA and that BCMA knockdown did not alter TACI levels in the investigators' CRISPR-Cas9 experiments. 
• Unresolved questions: TACI expression across clinically relevant MM subgroups has not been systematically defined, including in cells with irreversible BCMA and/or GPRC5D loss. 
• Future studies identified by the authors: Patient-based studies, particularly in patients whose disease has relapsed after BCMA- or GPRC5D-directed immunotherapy, are needed to further evaluate TACI × CD3 bsAb. 
 
Strengths
Activity was demonstrated across in vitro, in vivo, and primary patient-derived MM models. 
 
Limitations 
TACI expression across clinically relevant MM subsets remains incompletely characterized; responses among primary samples varied; the reason for the reduced activity against BCMA^KD tumors requires further investigation; and the clinical relevance of TACI expression after BCMA/GPRC5D loss remains unknown. 
 
Why this study matters 
The study found that TACI × CD3 bsAb can redirect T cells to exert cytotoxic effects against MM cells, including BCMA-low/knockdown cells that were resistant to BCMA × CD3 bsAb treatment. The findings support further investigation of TACI as a target for MM immunotherapy, while the authors identify the need to characterize TACI expression across clinically relevant MM populations and evaluate the approach in patient-based studies, particularly after BCMA- or GPRC5D-directed therapy. 
 
 
Reference: 
Minchuan Zhang, Wai Fook Leong, Jianxin Huo, Eve Zi Xian Ngoh, Hanping Loh, Qingfeng Chen, Sabrina H. M. Toh, Sanjay De Mel, Melissa Ooi, Cinnie Soekojo, Wee Joo Chng, Yuansheng Yang, Kong-Peng Lam, Shengli Xu; Engineering a TACI × CD3 bispecific antibody to redirect T cells against multiple myeloma. Blood Adv 2026; 10 (16): 5669–5682. doi: https://doi.org/10.1182/bloodadvances.2025018210 
 

Real-world treatment patterns and outcomes of patients treated with commercial chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma — Current Medical Research and Opinion (August 2026) 
 

What is the purpose of the real-world study? 
To characterize physician-reported prescribing and referral patterns for chimeric antigen receptor T-cell (CAR-T) therapy in patients with relapsed/refractory multiple myeloma (RRMM). It also describes treatment pathways and clinical outcomes among patients receiving commercial ciltacabtagene autoleucel (cilta-cel). 
 
Summary 
This two-part study combined a descriptive survey of 17 physicians with a retrospective medical chart review of 72 adults with RRMM who received commercial cilta-cel between February 28, 2022, and June 30, 2024; safety data were not captured. Physicians reported that 31%–50% of eligible patients were not referred for CAR-T therapy in 52.9% of practices, with efficacy (76.5%) and good performance status/low frailty (64.7%) among the leading reasons for referral, while patient choice (52.9%), poor performance status/high frailty (47.1%), comorbidity burden (41.2%), and older age (41.2%) were reported as primary reasons for nonreferral. Among patients receiving cilta-cel, 55.6% traveled >30 miles to treatment centers and 27.8% relocated; among those with a response assessment, the overall response rate was 95.2% and 60.3% achieved at least a complete response, while at a median follow-up of 5.6 months, 86.1% were alive and 43.5% were in remission without active treatment. 
 
Key points 
• Study design: Descriptive physician survey plus retrospective medical chart review within the Cardinal Health Oncology Provider Extended Network (OPEN). 
• Physician survey: 17 physicians participated; 82.4% practiced in private community settings and 17.6% in academic centers. 
• Referral patterns: Physicians reported treating 289 patients eligible for CAR-T therapy in the preceding year; 52.9% reported that 31%–50% of eligible patients were not referred. 
• Reported reasons for referral: Efficacy (76.5%) and good performance status/low frailty (64.7%) were the most frequently reported reasons. 
• Reported reasons for nonreferral: Patient choice (52.9%), poor performance status/high frailty (47.1%), comorbidity burden (41.2%), and older age (41.2%). 
• Treatment access: Among 72 patients receiving cilta-cel, 55.6% traveled >30 miles to a treatment center and 27.8% relocated for treatment. 
• Response: Among patients with a response assessment, the overall response rate was 95.2%, and 60.3% achieved at least a complete response. 
• Status at follow-up: At a median follow-up of 5.6 months, 86.1% of patients were alive; 43.5% were in remission and not receiving active treatment. 
 
Strengths 
Physician-abstracted chart data provided detailed clinical context and were intended to minimize misclassification and abstractor/responder bias; the geographically diverse OPEN network provided representation across community oncology settings; combining physician perspectives with patient chart data provided information on the treatment pathway. 
 
Limitations 
Participating physicians had prior experience referring patients for CAR-T, so their views may not represent all hematologic oncologists. The chart-review population consisted of patients selected for referral and subsequent cilta-cel infusion, limiting generalizability of post-infusion outcomes; clinical-variable completeness varied. The study was conducted within the US healthcare system, the physician survey may have recall and reporting bias, socioeconomic and other patient characteristics were not fully evaluated, and treatment practices may differ from contemporary practice. The relatively short median follow-up prevented assessment of long-term outcomes and multivariate or subgroup analyses, and safety data were not captured. 
 
Why this study matters 
The study describes physician-reported barriers and referral patterns for CAR-T therapy and treatment pathways among patients with RRMM receiving commercial cilta-cel in the US healthcare system. In the chart-reviewed population, the overall response rate was 95.2% among patients with a response assessment, 60.3% achieved at least a complete response, and 86.1% were alive at a median follow-up of 5.6 months; the authors state that the findings may inform clinical best practices and guidelines, payer decisions, and health-system planning, while noting the study's limited follow-up, selected patient population, variable data completeness, and absence of safety data. 
 
Reference: 
Fonseca, R., Brunner, M. J., Fanning, S., Nahas, G., Nagar, S. P., De Wiest, D., … Qureshi, Z. P. (2026). Real-world treatment patterns and outcomes of patients treated with commercial chimeric antigen receptor T-cell therapy for relapsed/refractory multiple myeloma. Current Medical Research and Opinion, 1–7. https://doi.org/10.1080/03007995.2026.2717477 

Real-world outcomes of daratumumab, bortezomib, thalidomide and dexamethasone (Dara-VTd) induction and lenalidomide maintenance in transplant-eligible multiple myeloma — British Journal of Haematology (August 2026) 
 

What is the purpose of the study? 
To evaluate the efficacy and survival outcomes of lenalidomide maintenance after Dara-VTd induction, autologous haematopoietic stem cell transplantation (AHSCT), and post-transplant consolidation in transplant-eligible patients with newly diagnosed multiple myeloma (TENDMM). It also explores overall survival (OS) compared with patients receiving daratumumab maintenance in the CASSIOPEIA trial. 
 
Summary 
This real-world analysis included 183 adults from 17 Brazilian centers and one Argentine centre who received Dara-VTd induction; 161 (88%) underwent AHSCT, and 137 patients who completed the specified treatment sequence were included in the landmark outcome analysis. Among 113 patients evaluable for response, 37.2% achieved complete response (CR) or better after consolidation, increasing to 58.4% at last follow-up; after a median follow-up of 42 months, the estimated 36-month time-to-next-treatment (TTNT) rate was 81.1% and OS rate was 94.1%. 
 
An exploratory comparison found no statistically significant difference in OS between the Dara-VTd–lenalidomide cohort and the CASSIOPEIA population receiving Dara-VTd followed by daratumumab maintenance, although the study populations differed in baseline characteristics. 
 
Key points 
• Population: 183 patients with newly diagnosed multiple myeloma and intent to undergo AHSCT; 88% ultimately underwent AHSCT. 
• Treatment sequence: Dara-VTd induction → AHSCT → two post-transplant consolidation cycles → continuous lenalidomide maintenance. 
• Maintenance timing: Median 11 months from diagnosis and 5 months after AHSCT to initiation of lenalidomide maintenance. 
• Responses among 113 evaluable patients: 
 - After consolidation: 37.2% CR or better, 40.1% VGPR, 4.4% PR. 
 - At last follow-up: 58.4% CR or better, 24.1% VGPR, 4.4% PR. 
• After median 42 months of follow-up: estimated 36-month TTNT 81.1% and 36-month OS 94.1% in the landmark analysis. 
• Intention-to-treat population (n=183): estimated 36-month OS was 88.8%. 
• Deaths: 10 patients died; 6 deaths were attributed to disease progression. Among four patients who had achieved CR or VGPR, one death was due to acute myeloid leukaemia and three to infection. 
• Exploratory comparison: OS did not differ statistically between the Dara-VTd–lenalidomide cohort and the CASSIOPEIA population receiving Dara-VTd followed by daratumumab maintenance. 
• MRD: MRD data were excluded because testing was performed in very few patients and assay sensitivity was not standardized. 
• CR assessment: The authors stated that CR rates were likely underestimated because anti-CD38 antibody therapy can interfere with immunofixation-based response assessment. 
 
Strengths 
The study provides a real-world assessment of a treatment sequence for which the authors state that randomized evidence is lacking. 
 
Limitations 
• Non-randomized design with inherent real-world biases. 
• Indirect cross-trial comparison, which the authors state cannot replace head-to-head randomized evidence. 
• Differences in baseline characteristics between the present cohort and CASSIOPEIA, particularly ECOG performance status and ISS stage distribution. 
• Limited and non-standardized MRD assessment, resulting in exclusion of MRD data. 
 
Why this study matters 
In this real-world cohort, sequential Dara-VTd induction followed by lenalidomide maintenance was associated with deepening responses and estimated 36-month OS of 94.1% among patients completing the treatment sequence, with 81.1% remaining without subsequent treatment at 36 months. The exploratory comparison with CASSIOPEIA found no statistically significant difference in OS versus daratumumab maintenance, but the non-randomized design, baseline differences, and indirect cross-trial comparison limit conclusions about comparative efficacy; the authors state that direct comparative studies are needed to define the optimal maintenance strategy. 
 
Reference: 
Crusoé, E.Q., Ribeiro, G., Souto Filho, J.T.D., Schmidt Filho, J., Schutz, N., Aranha, M.A.F., Costa, A., Hallack, A., Pericole, F.V., Lima, J.S., Gusmão, B., Ribeiro, E.F.O., Vaz, J.P., Bittencourt, R., Cunha, R., Ovigli, D., Berg, L., Mattos, E.R., Maiolino, A., Hungria, V. and GBRAM (2026), Real-world outcomes of daratumumab, bortezomib, thalidomide and dexamethasone (Dara-VTd) induction and lenalidomide maintenance in transplant-eligible multiple myeloma. Br J Haematol. https://doi.org/10.1111/bjh.70775 

 
Interim analysis in clinical trials: caution against premature conclusions—the SWOG multiple myeloma S0777 case study — Trials (August 2026) 
 

What is the purpose of the study? 
To examine how pre-planned interim efficacy and futility analyses can guide decisions about whether to stop randomized clinical trials early. Using the SWOG S0777 trial as a case study, it illustrates the potential consequences of stopping a trial prematurely when interim results do not show an early treatment benefit. 
 
Summary 
SWOG S0777 was a multicenter, open-label, randomized phase III trial comparing bortezomib, lenalidomide, and dexamethasone (VRd) with lenalidomide and dexamethasone (Rd) in 525 patients with newly diagnosed multiple myeloma. Although two pre-planned interim analyses showed minimal and seemingly diminishing evidence of improvement in progression-free survival (PFS), neither the pre-specified futility boundaries nor retrospectively evaluated alternative futility boundaries were crossed, and the trial continued to its planned final analysis. At final analysis, VRd significantly improved PFS (HR 0.71, p=0.0018) and overall survival (OS; HR 0.71, p=0.025) compared with Rd. 
 
Key points 
• Study design: Randomized phase III trial; 525 patients were randomized 1:1 to VRd (264) or Rd (261). 
• Primary objective: Determine whether adding bortezomib to lenalidomide and dexamethasone improved PFS in newly diagnosed multiple myeloma. 
• Interim monitoring: Two pre-planned interim analyses evaluated both efficacy and futility using PFS. 
• Interim findings: The accumulating data showed minimal and seemingly diminishing evidence of treatment benefit, but the pre-specified futility stopping boundaries were not crossed. 
• Final findings: VRd significantly improved: 
 - PFS: HR 0.71, p=0.0018 
 - OS: HR 0.71, p=0.025 
• Clinical relevance stated by the study: The final results contributed to establishing VRd as a standard of care. 
 
Strengths 
The study used pre-specified interim efficacy and futility analyses, allowing the trial to continue in accordance with its planned stopping rules despite unfavorable-looking interim results. 
 
Limitations 
The authors note early discontinuation of VRd due to neuropathy and difficulty assessing the prognostic contribution of age because age was not a stratification factor. 
 
Why this study matters 
The SWOG S0777 case study shows that interim analyses with pre-specified efficacy and futility boundaries can provide structured criteria for decisions about early trial termination. Despite limited and seemingly diminishing evidence of benefit at interim analyses, the trial continued because the futility boundaries were not crossed, and the final analysis demonstrated significant improvements in PFS and OS with VRd compared with Rd. 
 
Reference: 
Goren, E., Sexton, R., Orlowski, R.Z. et al. Interim analysis in clinical trials: caution against premature conclusions—the SWOG multiple myeloma S0777 case study. Trials 27, 550 (2026). https://doi.org/10.1186/s13063-026-09969-w 
 

Practical recommendations for the implementation of shared decision-making in multiple myeloma care — PLoS One (August 2028) 
 

What is the purpose of the study? 
To develop practical, stakeholder-informed recommendations for implementing shared decision-making (SDM) in multiple myeloma (MM) care. It focuses on translating SDM principles into guidance that addresses the complex and evolving treatment decisions experienced by patients with MM. 
 
Summary 
This European mixed-methods study, initiated by Myeloma Patients Europe, developed 24 initial recommendations from empirical research involving MM patients and healthcare professionals, then refined them through two online multi-stakeholder workshops involving patients, carers, hematologists, oncology nurses, and patient organization representatives from multiple European countries. The final set contained 10 core recommendations covering personalized patient involvement, tailored information, discussion of all treatment options including no treatment, multidisciplinary communication, patient preparation and partnership, continuity of care, and structural, educational, and organizational support for SDM. 
 
Key points 
• Study design: European mixed-methods research project combining empirical studies, multi-stakeholder workshops, qualitative thematic analysis, and iterative consensus discussions. 
• Participants: Patients, carers, hematologists, oncology nurses, and patient organization representatives from multiple European countries. 
• Recommendations: The final output comprised 10 core recommendations for implementing SDM in MM care. 
• Main areas addressed: 
 - Personalized and preference-sensitive patient involvement
 - Tailored provision of information
 - Open discussion of all treatment options, including no treatment
 - Stronger multidisciplinary communication
 - Patient preparation and partnership
 - Continuity of care 
 - Structural, educational, and organizational support. 

• Implementation requirements: Meaningful SDM may require sufficient consultation time, follow-up discussions, opportunities for patients to reflect on information, communication skills and training for healthcare professionals, staffing, privacy, documentation systems, care coordination, and organizational support. 
    
• Roles: SDM implementation involves healthcare professionals, nurses, healthcare organizations, patient organizations, and researchers, with different responsibilities for communication, continuity of care, structural support, educational materials, decision aids, and awareness-raising. 
    
• Context dependence: The authors state that applicability, feasibility, and relevance may vary across countries and healthcare systems because of differences in resources, professional roles, and the maturity of SDM implementation. The recommendations are intended as a best-practice guide rather than a rigid protocol. 

• Acute care: The authors note that SDM may not always be feasible during acute situations in which immediate treatment is required. 

Strengths
The study's mixed-methods design and active involvement of diverse stakeholders were identified by the authors as major strengths, supporting the relevance and credibility of the recommendations. 
 
Limitations 
• Workshop participation was limited to English-speaking stakeholders, which may have affected participant diversity. 
• Stakeholder representation was not optimal in each workshop because not every workshop included at least one participant from every stakeholder group. 
• Although the Nominal Group Technique (NGT) supported balanced participation and consensus building, the findings reflect the perspectives of study participants and do not necessarily represent consensus among all MM care stakeholders. 
• Participants considered prioritization of the recommendations infeasible because all were viewed as equally important; therefore, the 10 recommendations are presented in no specific order. 
• The real-world impact of the recommendations has not yet been evaluated in MM care trajectories. 
 
Why this study matters 
The study produced 10 multi-level recommendations intended to support implementation of SDM in MM care, addressing patient involvement, information provision, treatment-option discussions, communication, continuity, and organizational support. The authors state that applying these recommendations will require context-sensitive implementation and coordinated action across healthcare-system levels, and that their real-world impact and practical integration into routine MM care remain to be evaluated. 
 
Reference: 
Broekmans J, Schoefs E, Verbeke C, De Proost L, Ten Seldam S, Duncan E, Aviv A, Shoham V, Delforge M, Vanhellemont A, Huys I. Practical recommendations for the implementation of shared decision-making in multiple myeloma care. PLoS One. 2026 Aug 28;21(8):e0355283. doi: 10.1371/journal.pone.0355283. 
 
 

Bone Marrow Fibrosis as a Predictor of Extramedullary Disease in Multiple Myeloma — European Journal of Haematology (August 2026) 
 

What is the purpose of the study? 
To determine how often bone marrow fibrosis (BMF) occurs in patients with newly diagnosed multiple myeloma (NDMM) and to evaluate its relationship with synchronous soft-tissue extramedullary disease (EMD) at diagnosis. 
 
Summary 
This retrospective single-center study analyzed 356 patients with multiple myeloma; BMF was graded using World Health Organization criteria, with Grade 2–3 classified as fibrosis and Grade 0–1 as non-fibrosis. Grade 2–3 BMF was present in 146 patients (41%), while EMD was identified in 52 (14.6%) and paraskeletal plasmacytoma in 54 (15.2%). Among patients with EMD, 40/52 had Grade 2–3 BMF, and multivariable logistic regression identified BMF status (OR 3.200, 95% CI 1.010–10.141; p=0.048) and elevated serum lactate dehydrogenase (LDH) (OR 1.003, 95% CI 1.000–1.005; p=0.037) as independent predictors of synchronous EMD. 
 
Key points 
• Study population: 356 patients with multiple myeloma. 
• BMF: 146 patients (41%) had Grade 2–3 BMF. 
• Extramedullary disease: EMD was present in 52 patients (14.6%); paraskeletal plasmacytoma was present in 54 (15.2%). 
• Association with EMD: Grade 2–3 BMF was observed in 40 of 52 patients with EMD (p<0.01). 
• Among 210 patients without BMF, EMD was absent in 198 (p<0.01). 
• Multivariable analysis: BMF status (OR 3.200, 95% CI 1.010–10.141; p=0.048) and elevated serum LDH (OR 1.003, 95% CI 1.000–1.005; p=0.037) were independently associated with synchronous EMD. 
• The study reports that patients with increased BMF also had advanced ISS stages, higher bone marrow plasma cell burden, elevated LDH, hypercalcemia, increased β2-microglobulin, accelerated erythrocyte sedimentation rate, lower hemoglobin, and lower platelet counts. 
• In the IgD myeloma subgroup, 6 of 9 patients had EMD, and all 6 had concurrent advanced BMF. 
 
Strengths 
The authors describe the study as one of the largest single-center cohorts examining the relationship between BMF and EMD and state that its larger population provided greater statistical power than previously published small series. 
 
Limitations  
The study was retrospective and single-center, which may limit generalizability. BMF grading may have interobserver variability. Because baseline parameters were evaluated retrospectively, the study demonstrates a cross-sectional association with synchronous EMD, rather than predicting later EMD development. The authors state that prospective studies with longitudinal follow-up are needed for validation. 
 
Why this study matters 
In this cohort of 356 patients with multiple myeloma, advanced BMF was associated with synchronous EMD at diagnosis, with BMF status and elevated serum LDH independently associated with EMD in multivariable analysis. The authors conclude that systematic assessment and grading of BMF at initial diagnosis may provide a surrogate marker for identifying patients with concurrent extramedullary involvement, while noting that prospective longitudinal studies are needed to validate the findings. 
 
 
Reference: 
H. Senkal, A. Y. Altay, E. G. Isik, et al., “Bone Marrow Fibrosis as a Predictor of Extramedullary Disease in Multiple Myeloma,” European Journal of Haematology (2026): 1–6, https://doi.org/10.1111/ejh.70314. 

Dynamic Prediction of Survival Outcomes in Multiple Myeloma — Cancers (September 2026) 

What is the purpose of the study? 
To develop and validate a gene-expression–based risk score for predicting survival in patients with multiple myeloma (MM) at diagnosis and at later stages of disease. The model was designed to account for changes in disease biology over time and complement established risk measures such as the International Staging System (ISS) and FISH-defined cytogenetic risk. 
 
Summary 
Researchers used transcriptomic data from 762 newly diagnosed MM patient samples in the MMRF CoMMpass study (NCT01454297) to evaluate activity across 469 cancer-relevant pathways and construct a Bayesian network associated with survival. The resulting score incorporated five pathways—unfolded protein response (UPR), FLT3 signaling through SRC family kinases, G2M DNA replication checkpoint, metabolism of selenium compound (SeMet), and nicotinate metabolism—and was validated in 1,255 patients from five independent diagnostic cohorts and 319 patients from two post-treatment or relapsed/refractory cohorts. High-risk patients had shorter survival (median 1170 days vs. not reached; p<0.0001), and the score remained independently associated with survival after adjustment for age, sex, ISS stage, and KRAS, TP53, and UBR5 mutation status (HR 4.93, 95% CI 2.96–8.19; p<0.001). 
 
Key points 

• Study population and validation 
 - Discovery cohort: 762 newly diagnosed MM samples from MMRF CoMMpass (NCT01454297). 
 - Five independent diagnostic cohorts: 1,255 patients. 
 - Two independent previously treated or relapsed/refractory cohorts: 319 patients. 
 - Longitudinal analysis: 46 patients with serial pre- and post-treatment samples. 
    
• Risk model 
 - The model evaluated 469 non-redundant cancer-relevant pathways using transcriptomic data and a Bayesian network. 
 - Five pathways were directly associated with the survival outcome: UPR, FLT3/SRC-family kinase signaling, G2M DNA replication checkpoint, SeMet metabolism, and nicotinate metabolism. 
 - The continuous score was used as the prognostic index; cohort-specific cutoffs were used for risk-group visualization. 
    
• Survival findings 
 - 76 patients (10%) were classified as high risk. 
 - Median survival was 1170 days in the high-risk group versus not reached in the standard-risk group (p<0.0001). 
 - The score remained independently associated with survival after adjustment for clinical and molecular factors: HR 4.93 (95% CI 2.96–8.19; p<0.001). 
 - Prognostic discrimination was replicated across all five independent diagnostic cohorts. 
 - The score also retained prognostic discrimination in previously treated (GSE57317; p<0.0001) and relapsed/refractory disease (GSE9782; p<0.0001). 
    
• Longitudinal findings 
 - Patients whose risk classification changed from standard risk to high risk after treatment had significantly poorer survival than patients who remained standard risk. 
 - Patients with stable high-risk status did not have significantly different survival from those transitioning from standard to high risk; however, the stable high-risk group contained only four patients, limiting statistical power. 
 
Strengths  
• The model was evaluated across multiple independent cohorts and different treatment settings. 
• The score retained prognostic validity in diagnostic, post-treatment, and relapsed/refractory settings. 
• The model provided information complementary to ISS and FISH-defined cytogenetic risk. 
 
Limitations  
• The discovery and most validation cohorts used CD138-selected bulk RNA-sequencing or microarray platforms, and cross-platform applicability requires further methodological harmonization. 
• Treatment regimens differed across cohorts and eras, which may confound post-treatment analyses. 
• The serial cohort was small, so the dynamic-tracking findings are considered exploratory and require confirmation in larger longitudinal studies. 
• All analyses were retrospective and require prospective evaluation. 
• The available cohorts did not include patients treated with daratumumab or other CD38-targeted quadruplet regimens. 
• The study lacked MRD measurements and sufficiently structured longitudinal treatment-response data, so whether the score predicts MRD persistence, early relapse, or frontline treatment resistance remains unknown. 
• Serial samples were collected at clinically defined time points rather than according to a prespecified surveillance schedule; therefore, the study could not establish whether molecular risk classification provides earlier information than conventional measures of disease progression. 
• The biological evidence for the five pathways was not uniform; the roles of FLT3/SRC, selenium metabolism, and nicotinate metabolism in MM were described as less established and hypothesis-generating. 
 
Why this study matters 
The study developed a five-pathway Bayesian network–based survival score that showed reproducible prognostic associations in newly diagnosed, previously treated, and relapsed/refractory MM cohorts. The score also identified changes in risk status after treatment, but the longitudinal findings are exploratory because of the small serial cohort and retrospective study design. Prospective validation, including serial transcriptomic profiling together with MRD and treatment-response measurements, is required to determine its clinical utility and whether it provides information beyond established risk measures. 
 
Reference: 
Quek, K., Lee, C. H., Zhang, Y., McClure, B. J., Chen, R., Scott, H. S., Vandyke, K., Zannettino, A. C. W., & Kok, C. H. (2026). Dynamic Prediction of Survival Outcomes in Multiple Myeloma. Cancers, 18(17), 2864. https://doi.org/10.3390/cancers18172864 
 

Real-world minimal residual disease assessment in multiple myeloma using a standardized flow cytometry approach: feasibility, clinical implications, and immune correlates from a single-center experience — Haematologica (September 2026) 

 
What is the purpose of the study? 
To assess whether standardized EuroFlow-based next-generation flow cytometry (NGF) using two CE-IVD-approved tubes could feasibly detect minimal residual disease (MRD) in routine clinical practice in patients with multiple myeloma (MM). It also examines the relationship between bone marrow (BM) immune-cell profiles and MRD status and clinical outcomes. 
 
Summary 
Between December 2021 and February 2024, 74 patients with MM underwent 97 MRD assessments after achieving at least a very good partial response (VGPR); 58 patients were transplant-eligible. Using at least 2 million events per sample, NGF achieved a median sensitivity of 10⁻⁵, and 45% of assessments were MRD-undetectable (uMRD). After a median follow-up of 19 months, there was 1 relapse among uMRD patients, compared with 15 relapses and 3 deaths among patients with persistent MRD (pMRD). 
 
Key points 
• MRD method: Two CE-IVD-approved EuroFlow tubes were used for standardized NGF-based MRD assessment in a real-world clinical setting. 
• Patients/assessments: 74 patients with MM; 97 MRD evaluations performed after achievement of at least VGPR. 
• Transplant eligibility: 58 patients were classified as transplant-eligible. 
• Analytical sensitivity: A median sensitivity of 10⁻⁵ was achieved using ≥2 million events/sample; the reported limit of detection (LOD) was 1 × 10⁻⁵. 
• MRD status: 45% of assessments showed uMRD. 
• Clinical outcomes: During a median 19-month follow-up, 1 relapse occurred in the uMRD group, compared with 15 relapses and 3 deaths in the pMRD group. 
• Bone marrow immune profile: uMRD patients had a higher granulocyte-to-lymphocyte ratio and a lower proportion of CD56dim natural killer (NK) cells than patients with persistent MRD. 
• Exploratory analysis: The immune-profiling analysis was a post-hoc analysis of a limited patient subset with available flow-cytometry data (FCS files). The observed immune associations were described by the authors as hypothesis-generating rather than definitive predictive biomarkers. 
• Reproducibility: No significant differences in marker mean fluorescence intensity (MFI) were observed between samples processed within 24 hours and those processed between 24 and 48 hours after collection, with lymphocyte populations used as internal biological controls. 
• NGF versus NGS: The authors describe NGF and next-generation sequencing (NGS) as having different advantages and limitations: NGS provides high sensitivity and patient-specific molecular-marker detection, whereas NGF provides rapid turnaround and immune-profile information. The authors note that the methods may be complementary. 
• Treatment implications discussed: The authors relate standardized MRD assessment to current and potential MRD-driven treatment strategies, including treatment de-escalation, and cite the PERSEUS trial as an example of an MRD-guided treatment approach. This study itself did not establish such a treatment strategy. 
 
Strengths 
• Use of standardized, CE-IVD-approved commercial EuroFlow tubes for NGF-based MRD assessment in a real-world clinical setting. 
• Assessment of MRD using a standardized workflow with a reported LOD of 1 × 10⁻⁵. 
• Inclusion of bone marrow immune profiling and a semi-automated computational approach for single-cell-level characterization. 
• Evaluation of sample-processing robustness across ≤24 hours versus 24–48 hours after collection. 
 
Limitations 
• Single-center study with both prospective and retrospective components, potentially introducing selection and reporting biases and limiting generalizability. 
• Relatively small sample size, limiting statistical power, particularly for subgroup and longitudinal analyses. 
• MRD assessments occurred at different clinical timepoints, including post-induction, post-ASCT, and follow-up, introducing heterogeneity in MRD interpretation. 
• The sample size and clinical heterogeneity prevented robust comparisons across treatment strategies and comprehensive assessment of sustained MRD negativity over time. 
• 19-month median follow-up may be insufficient to evaluate long-term outcomes, particularly overall survival. 
• The small number of progression events among uMRD patients prevented definitive conclusions about durability of response in this subgroup. 
• Immune-profiling analyses were limited by the available sample size and their exploratory nature, restricting immediate generalizability. 
• A trend between IgG isotype and MRD persistence did not reach statistical significance and therefore requires validation in independent cohorts. 
 
Why this study matters 
The study found that standardized NGF using two CE-IVD-approved EuroFlow tubes was feasible for MRD assessment in routine clinical practice, with a reported LOD of 1 × 10⁻⁵ and uMRD identified in approximately 45% of assessments. uMRD was associated with fewer observed relapses during the 19-month median follow-up, while exploratory BM immune profiling identified differences in the granulocyte-to-lymphocyte ratio and CD56dim NK-cell proportion; however, the authors emphasize that these immune findings are hypothesis-generating. Larger prospective multicenter studies with longer follow-up are needed to further establish the prognostic and therapeutic implications of NGF-based MRD assessment and its integration with immune profiling and NGS. 
 
Reference: 
Botta C, Rizzuto A, Speciale M, Gigliotta E, Corsale AM, Romano F, Mussotto I, Aquilina C, Romano A, Biondo M, Tofacchi E, Di Simone M, Sciortino M, Brucato F, Guercio G, Di Caro M, Merenda A, Vasta S, Scazzone C, Bivona G, Calò V, La Manna MP, Caccamo N, Dieli F, Siragusa S, Meraviglia S. Real-world minimal residual disease assessment in multiple myeloma using a standardized flow cytometry approach: feasibility, clinical implications, and immune correlates from a single-center experience. Haematologica; https://doi.org/10.3324/haematol.2026.300864 [Early view]. 
 
 

Outcomes of CAR T-cell Therapy and Bispecific Antibodies as Single-Modality and Sequential Strategies in Relapsed/Refractory Multiple Myeloma — Blood Cancer Discovery (September 2026) 
 

What is the purpose of the study? 
To evaluate how treatment sequencing with chimeric antigen receptor (CAR) T-cell therapies and bispecific antibodies (BsAbs) was associated with clinical outcomes in 640 patients with relapsed/refractory multiple myeloma (RRMM). It specifically examines whether starting with CAR T or BsAb treatment, and subsequently receiving the other modality, was associated with differences in remission, progression-free survival (PFS), and overall survival (OS). 
 
Summary 
This retrospective, multicenter European real-world study analyzed 640 patients with RRMM who received CAR T-cell therapies—idecabtagene vicleucel (ide-cel), ciltacabtagene autoleucel (cilta-cel), or cesnicabtagene autoleucel (cesni-cel)—or BsAbs, using statistical methods to adjust for treatment-selection bias. Starting with CAR T was associated with longer remission and better PFS than starting with BsAbs, with the strongest product-level outcomes observed with cilta-cel and cesni-cel; however, mortality after progression was similar regardless of the initial treatment modality. Sequential treatment with both modalities appeared favorable in unadjusted analyses, but landmark analysis did not demonstrate a statistically significant sequential benefit (HR, 0.82 for CAR T→BsAb vs CAR T alone), and the authors state that prospective trials are needed to establish the independent effect of treatment sequencing. 
 
Key points 
• Population: 640 patients with relapsed/refractory multiple myeloma in a large, multicenter European real-world cohort. 
• Treatments evaluated: CAR T-cell therapies (ide-cel, cilta-cel, cesni-cel) and bispecific antibodies (BsAbs), including their sequencing. 
• Initial treatment: 
 - Starting with CAR T was associated with longer remission and better PFS than starting with BsAbs. 
 - The reported PFS advantage remained after adjustment for factors including age, extramedullary disease (EMD), ECOG performance status, cytogenetics, penta-refractoriness, and time from diagnosis to treatment. 
    
• CAR T products: 
 - Cilta-cel: CR rate 69%; 12-month PFS 86%. 
 - Cesni-cel: CR rate 60%; 12-month PFS 69%. 
 - The discussion states that the observed CAR T benefit appeared to be driven by cilta-cel and cesni-cel, while BsAbs had at least comparable outcomes with ide-cel. 
    
• After disease progression: The hazard of death was reported to be virtually identical regardless of whether CAR T or BsAb was given first. The OS advantage of CAR T-first strategies was primarily attributed to better first-line disease control (HR for progression, 0.79). 
    
• Access to subsequent treatment: 48% of CAR T-first patients received BsAb after progression, compared with 17% of BsAb-first patients who subsequently received CAR T. In the BsAb-first group, 22% remained progressed without second-line immunotherapy, compared with 5% in the CAR T-first group. 
    
• High-risk patients: Patients with EMD and those with ECOG ≥2 had worse outcomes with both modalities; the relative PFS benefit associated with CAR T over BsAbs was nevertheless maintained in these groups. 
    
• Safety: BsAbs were generally better tolerated, with lower rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cesni-cel had a toxicity profile described as comparable with BsAbs, whereas CAR T treatment overall involved logistical and safety considerations including leukapheresis, manufacturing delays, bridging therapy, CRS, ICANS, and delayed neuro- and gastrointestinal toxicities. 
    
• Nonrelapse mortality: Despite lower acute toxicity, BsAb treatment was not associated with lower nonrelapse mortality in this cohort; the authors caution that this finding may be confounded by relatively small sample sizes and other factors. 
    
• Treatment access: More than 80% of BsAb-treated patients had no access to CAR T because of systemic limitations rather than clinical ineligibility. 
 
Strengths  
• Large, multicenter, real-world European cohort. 
• Statistical adjustment using inverse probability of treatment weighting (IPTW), multistate modeling, landmark analyses, and rank-preserving structural failure time model (RPSFTM) sensitivity analysis. 
• Inclusion of patients who received BsAbs without access to CAR T because of treatment barriers, providing data on real-world treatment patterns without CAR T crossover. 
• Different analytical approaches converged on the reported association between CAR T exposure and survival. 
 
Limitations 
• Retrospective, nonrandomized design with potential selection bias and residual confounding from unmeasured factors, including prior treatment history, disease biology, and physician preference. 
• Treatment allocation was largely access-driven. 
• Immortal time bias could not be completely excluded. 
• First-line PFS was used as a proxy for resistance because granular molecular data, such as BCMA expression and T-cell functionality, were unavailable. 
• Product-level comparisons may be affected by differences in patient characteristics, dosing schedules, and institutional experience. 
• Lower BsAb CR rates may partly reflect less frequent confirmatory bone marrow assessment in routine practice. 
• The BsAb→CAR T subgroup was relatively small (n=41), limiting estimates for this treatment trajectory. 
• Follow-up may have been insufficient to capture long-term outcomes or late toxicities. 
• The BsAb cohort's infection-related mortality may have been influenced by enrollment during the later phases of the COVID-19 pandemic. 
• The landmark analysis did not establish a statistically significant sequential benefit, and prospective validation is required. 
 
Why this study matters 
In this real-world cohort, initiating treatment with CAR T was associated with longer remission and better first-line disease control than initiating treatment with BsAbs, with the observed CAR T benefit particularly associated with cilta-cel and cesni-cel. Although sequential use of CAR T and BsAbs appeared favorable in some analyses, the independent benefit of a specific treatment sequence was not established, and the authors conclude that prospective trials are needed to determine optimal sequencing. The study also identified treatment access and logistical barriers to CAR T as important factors affecting subsequent therapy and observed outcomes. 
 
Reference: 
Maximilian Merz, Tomas Jelinek, Thomas Pabst, Raphael Teipel, Anca-Maria Albici, Bastian von Tresckow, Marcel Teichert, Uta Margareta Demel, Antonia Busse, Marie Christine Wesener, Tobias A.W. Holderried, Friederike Schmitz, Friedrich-Linus Rößiger, Fabian Müller, Michele Hoffmann, Friedrich Stölzel, Natalia Tovar, Ben-Niklas Baermann, Martin Stork, Alexandra Jungova, Jiri Minarik, Jakub Radocha, Ivan Spicka, Ludek Pour, Polona Novak, Klara Slajpah, Karla Rener, Ulrich Keller, Stephan Bohl, David Fandrei, Patrick Born, Vladan Vučinić, Nicolaus Kröger, Irene Strassl, Natalie Schub, Roman Hájek, Matjaž Sever, Carlos Fernández de Larrea, Nico Gagelmann; Outcomes of CAR T-cell Therapy and Bispecific Antibodies as Single-Modality and Sequential Strategies in Relapsed/Refractory Multiple Myeloma. Blood Cancer Discov 1 September 2026; 7 (5): 697–710. https://doi.org/10.1158/2643-3230.BCD-25-0461 
 
 

Exposure-response and dose simulation of belantamab mafodotin in combination with standards of care in patients with relapsed/refractory multiple myeloma — Haematologica (September 2026) 

What is the purpose of the study? 
To evaluate the relationship between belantamab mafodotin exposure, efficacy, and ocular safety in relapsed/refractory multiple myeloma (RRMM) to inform dosing strategies. It also uses simulations to assess whether starting at 2.5 mg/kg followed by dose reductions and/or extended dosing intervals could balance efficacy and tolerability. 
 
Summary 
Exposure-response analyses using data from DREAMM-6, DREAMM-7, and DREAMM-8 found that higher Cycle 1 belantamab mafodotin exposure was associated with higher probabilities of overall response and very good partial response or better (≥VGPR), shorter time to response, and increased ocular events, including grade ≥2/≥3 ophthalmic exam findings (OEFs) and best-corrected visual acuity (BCVA) worsening to 20/50 or worse in both eyes. Multivariate modeling predicted a ≥VGPR probability of 70.4% with a 2.5 mg/kg starting dose versus 54.3% with 1.9 mg/kg, while the 2.5 mg/kg dose was associated with modest increases in some ocular outcomes. Simulations indicated that starting at 2.5 mg/kg followed by step-down dosing to 1.9 mg/kg and/or schedule extensions could retain meaningful efficacy while improving tolerability. 
 
Key points 
• Efficacy 
 - Higher first-dose belantamab mafodotin exposure was significantly associated with deeper responses, including ≥VGPR, and shorter time to response. 
 - The modeled probability of ≥VGPR was 70.4% with a 2.5 mg/kg starting dose versus 54.3% with a 1.9 mg/kg starting dose. 
 - In the analysis discussed, lowering the starting dose from 2.5 mg/kg to 1.9 mg/kg was associated with reductions in modeled efficacy without substantial improvements in ocular safety. 
    
• Ocular safety 
 - Higher exposure was associated with higher probabilities of grade ≥2/≥3 OEFs and BCVA worsening to 20/50 or worse in both eyes. 
 - Compared with 1.9 mg/kg, the 2.5 mg/kg starting dose was predicted to have no difference in grade ≥3 ocular adverse events, a 6% higher probability of BCVA worsening to 20/50 or worse in both eyes, and an 8% higher probability of grade ≥3 OEFs. 
 - In DREAMM-7 and DREAMM-8, ocular adverse-event rates were similar in patients with and without baseline ocular conditions: 74% vs 79% in DREAMM-7 and 87% vs 91% in DREAMM-8. 
    
• Dosing simulations 
 - Simulations of the DREAMM-7 regimen produced results similar to observed DREAMM-7 data: ≥VGPR 61.5% vs 66.0%, 12-month PFS 80.3% vs 78.0%, and grade ≥3 OEFs 85.5% vs 74.0% (simulated vs observed). 
 - Alternative regimens using a 2.5 mg/kg first dose, followed by step-down dosing and/or schedule extensions, showed meaningful efficacy with reduced ocular-event rates in simulations. 
 - The FDA-approved BVd regimen described in the study uses 2.5 mg/kg every 3 weeks (Q3W), with reduction to 1.9 mg/kg Q3W after a grade ≥2 OEF and extension to 1.9 mg/kg every 8 weeks (Q8W) after a second grade ≥2 OEF. 

Strengths  
• The exposure-response analysis included data from three combination regimens across two phase 3 trials and a dose-optimization study, allowing evaluation across multiple treatment settings. 
• Multiple safety endpoints were evaluated. 
• The simulation models incorporated data from several studies and were verified against results from DREAMM-7 and DREAMM-8. 
 
Limitations  
• The exposure-response analyses did not account for exposure to the combination-treatment partners. 
• The efficacy models did not separately evaluate the contribution of individual combination agents; therefore, efficacy could have been underpredicted for regimens with longer dosing intervals. 
• The simulation results are hypothesis-generating only, and clinical studies are required to confirm alternative dosing regimens. 
• Baseline ocular conditions were not assessed as part of the exposure-response analysis. 
 
Why this study matters 
In RRMM, higher first-dose belantamab mafodotin exposure was associated with deeper responses, including ≥VGPR, as well as increased probabilities of certain ocular events. The analyses and simulations supported a 2.5 mg/kg starting dose, with subsequent dose reduction and/or schedule extension as approaches to manage tolerability while maintaining meaningful efficacy; prospective studies, including DREAMM-15, are ongoing to evaluate lower dose intensities and alternative schedules. 
 
Reference: 
Lonial S, Richardson PG, Ferron-Brady G, Carreño F, Papathanasiou T, Ho YL, McKeown A, Brock K, Roy-Ghanta S, Melhem M, Mukhopadhyay P, Abdullah HA, Mateos M-V, Dimopoulos MA. Exposure-response and dose simulation of belantamab mafodotin in combination with standards of care in patients with relapsed/refractory multiple myeloma. Haematologica; https://doi.org/10.3324/haematol.2026.301229 [Early view]. 
 
 

Construction and Validation of a Progression-Free Survival Prediction Model for Newly Diagnosed Multiple Myeloma Patients With 1q21 Gain/Amplification — Cancer Medicine (September 2026) 

What is the purpose of the study? 
To identify clinical and genetic factors associated with progression-free survival (PFS) in newly diagnosed multiple myeloma (NDMM) patients with 1q21 gain/amplification (1q21+), and to develop and internally validate a prediction model, the HLBP nomogram, for individualized PFS risk stratification. 
 
Summary 
This single-center retrospective study included 186 patients with 1q21+ NDMM diagnosed between 2018 and 2024. Multivariable Cox regression identified hemoglobin (Hb), lactate dehydrogenase (LDH), β2-microglobulin (β2-MG), and TP53 deletion as prognostic factors, which were incorporated into the HLBP model; its time-dependent AUCs at 6, 12, and 24 months were 0.805, 0.885, and 0.847 in the training cohort and 0.747, 0.827, and 0.712 in the internal validation cohort. High- and low-risk groups defined by the model had significantly different PFS outcomes, while treatment-related analyses of induction regimens and autologous stem cell transplantation (ASCT) were exploratory. 
 
Key points 
• Study population: 186 NDMM patients with FISH-confirmed 1q21+, treated at a single center from August 2018 to August 2024; median follow-up was 31.5 months (range, 4.2–59.0 months). 
• Model development: Patients were randomly divided into a training cohort (n=131) and an internal split-sample validation cohort (n=55). 
• Independent prognostic factors: 
 - Higher Hb was associated with more favorable PFS. 
 - Higher LDH was associated with less favorable PFS. 
 - Higher β2-MG was associated with less favorable PFS. 
 - TP53 deletion was associated with less favorable PFS. 
    
• HLBP model performance: 
 - Training cohort AUC: 0.805 at 6 months, 0.885 at 12 months, and 0.847 at 24 months. 
 - Internal validation cohort AUC: 0.747 at 6 months, 0.827 at 12 months, and 0.712 at 24 months. 
 - Calibration and bootstrap analyses were performed, and a LASSO Cox sensitivity analysis showed generally consistent variable-selection results. 
    
• Risk stratification: The HLBP score separated patients into high- and low-risk groups with significantly different PFS outcomes. 
• Treatment-related exploratory findings: Associations between induction regimens or ASCT and PFS differed across HLBP-defined risk groups. These analyses were conducted after model development and were not designed to establish causal treatment effects or definitive treatment recommendations. 
 
Strengths 
The study used bootstrap resampling and an internal validation cohort for model evaluation, and LASSO Cox regression was used as a sensitivity analysis to assess the robustness of variable selection. 
 
Limitations 
• Single-center, retrospective design. 
• Relatively limited cohort size. 
• No independent external validation. 
• The internal validation cohort was small, potentially making AUC estimates and subgroup analyses less stable. 
• Univariate screening before multivariable modeling may introduce variable-selection instability and exclude clinically relevant factors that were not statistically significant in univariate analysis. 
• Treatment heterogeneity and potential treatment-allocation bias may have influenced PFS. 
• Treatment-related subgroup analyses were exploratory. 
 
Why this study matters 
The HLBP nomogram, incorporating Hb, LDH, β2-MG, and TP53 deletion, demonstrated preliminary ability to predict PFS and distinguish risk groups among patients with 1q21+ NDMM in this cohort. Its performance was reported as superior to conventional staging systems and previously published prognostic models within the study, but the findings require confirmation through larger, multicenter prospective studies with independent external validation. 
 
Reference: 
Y. Rao, S. Li, A. Yu, et al., “Construction and Validation of a Progression-Free Survival Prediction Model for Newly Diagnosed Multiple Myeloma Patients With 1q21 Gain/Amplification,” Cancer Medicine 15, no. 9 (2026): e72077, https://doi.org/10.1002/cam4.72077. 
 
 

Real-world outcomes with BCMA- and GPRC5D-targeting bispecific antibodies in plasma cell leukemia — Blood Advances (September 2026) 
 

What is the purpose of the study? 
To evaluate the effectiveness and safety of T-cell–redirecting bispecific antibodies (BsAbs) in patients with primary or secondary plasma cell leukemia (PCL), a population generally excluded from pivotal BsAb trials. It specifically examines outcomes according to PCL status at treatment and compared BCMA-directed therapies (teclistamab and elranatamab) with GPRC5D-directed therapy (talquetamab). 
 
Summary 
This multicenter retrospective study included 122 patients treated at 15 U.S. academic centers with teclistamab (37%), elranatamab (11%), or talquetamab as a line of therapy (Tal LOT, 42%) or as a bridge to CAR T-cell therapy (Tal Bridge, 11%). The overall response rate was 55%; grade 3–4 cytokine release syndrome occurred in 4% and grade 3–4 neurotoxicity in 5% of patients, with no deaths attributed to either complication.   With a median follow-up of 8.3 months, Tal LOT had a median progression-free survival (mPFS) of 5.5 months and median overall survival (mOS) of 11.5 months, compared with mPFS/mOS of 1.2/8.1 months for teclistamab and 1.6/3.6 months for elranatamab; among patients with active PCL, Tal LOT had mPFS/mOS of 6.9/12.2 months, versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab. 
 
Key points 
• Study population: 122 adults with primary or secondary PCL treated with BCMA- or GPRC5D-directed BsAbs across 15 U.S. academic centers. 
• Disease status: Patients were classified as having active PCL if ≥5% circulating plasma cells were present within 30 days before or after BsAb initiation; otherwise, prior PCL was classified as historical PCL. 
• Treatments: Teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (42%), and talquetamab as a bridge to CAR T-cell therapy (11%). 
• Response: Overall response rate was 55%: 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. 
• Safety: Grade 1–2 cytokine release syndrome (CRS) occurred in 56% and grade 3–4 CRS in 4%; grade 1–2 neurotoxicity occurred in 16% and grade 3–4 neurotoxicity in 5%. No deaths were attributed to CRS or neurotoxicity. 
• Overall survival outcomes: Tal LOT had mPFS/mOS of 5.5/11.5 months; both endpoints were unreached in the Tal Bridge group. Teclistamab had 1.2/8.1 months, and elranatamab had 1.6/3.6 months. 
• Active PCL: Tal LOT had mPFS/mOS of 6.9/12.2 months, compared with 0.7/1.4 months for teclistamab and 1.0/3.1 months for elranatamab. 
• Multivariable analysis: Active PCL was independently associated with worse PFS and OS, while definitive GPRC5D-directed therapy was associated with improved PFS and OS. 
 
Strengths  
The study included a relatively large real-world, multicenter cohort of 122 patients across 15 academic centers, addressing a population excluded from pivotal BsAb trials; sensitivity analyses excluding the Tal Bridge cohort yielded consistent results. 
 
Limitations  
The retrospective, multicenter design introduced variability in data collection, missing data, lack of randomization, and heterogeneity in dosing and schedules. The study also lacked translational data on soluble BCMA (sBCMA) levels, limiting assessment of their potential contribution to resistance to BCMA-directed therapies. 
 
Why this study matters 
In this real-world cohort of patients with PCL, BsAbs had an acceptable safety profile, with severe CRS and neurotoxicity occurring in 4% and 5% of patients, respectively. Talquetamab, particularly when used as a definitive line of therapy, was associated with longer PFS and OS than the BCMA-directed BsAbs teclistamab and elranatamab, with the difference most pronounced in patients with active PCL. 
 
Reference: 
Mahmoud R. Gaballa, Kelley Julian, Aimaz Afrough, Doris K. Hansen, Utkarsh Goel, Andre De Menezes Silva Corraes, Danai Dima, Masooma Rana, Hitomi Hosoya, Lekha Mikkilineni, Lindsay Fogel, Shahzad Raza, Rahul Banerjee, Saurabh S. Zanwar, Oren Pasvolsky, Aishwarya Sannareddy, Azra Borogovac, James Davis, Kimberly Green, Noa Biran, Eli Zolotov, Megan Herr, Leyla Shune, Evguenia Ouchveridze, Shaun DeJarnette, Shebli Atrash, Christopher Ferreri, Tiffany Richards, Muhammad Bilal Abid, Susan Bal, Hossam M. Ali, Jing Christine Ye, Shambavi Richard, Gurbakhash Kaur, Kenneth Shain, Omar Castaneda-Puglianini, Ken Harada, Gabriel De Avila, Adriana Rossi, Hamza Hassan, Larry D. Anderson, Peter M. Voorhees, Jack Khouri, Surbhi Sidana, Andrew J. Portuguese, Murali Janakiram, Hans C. Lee, Yi Lin, Ariel Grajales-Cruz, Krina K. Patel, Douglas W. Sborov; Real-world outcomes with BCMA- and GPRC5D-targeting bispecific antibodies in plasma cell leukemia. Blood Adv 2026; 10 (17): 5938–5950. doi: https://doi.org/10.1182/bloodadvances.2026020826 

TNFRSF17 genomic profiling guides retreatment with alternative BCMA-directed immunotherapies in multiple myeloma — Blood Advances (September 2026) 
 

What is the purpose of the study? 
To evaluate whether targeted next-generation sequencing of TNFRSF17 (BCMA) at clinical relapse after BCMA-directed therapy could identify tumor-intrinsic genetic resistance mechanisms in patients with multiple myeloma (MM). It also examines whether these genomic findings could inform the selection and sequencing of subsequent BCMA-directed treatments in routine clinical practice. 
 
Summary 
This case series included 5 patients with MM who developed clinical relapse after BCMA-directed therapy, including teclistamab, elranatamab, idecabtagene vicleucel, and linvoseltamab. Targeted sequencing at relapse identified acquired TNFRSF17 alterations, including extracellular-domain mutations, focal monoallelic deletions, and, in one patient, complete biallelic loss of the TNFRSF17 locus; these alterations had not been detected at diagnosis. In 2 patients, the genomic findings directly informed subsequent treatment: one patient without a detectable BCMA alteration achieved a very good partial response (VGPR) with linvoseltamab after idecabtagene vicleucel, while another with an acquired p.Y13N mutation received elranatamab and achieved a VGPR lasting 4 months before progression coincided with biallelic TNFRSF17 deletion. 
 
Key points 
• Study population: 5 patients with MM who had received 1–8 previous lines of therapy before BCMA-directed treatment. 
• BCMA-directed treatments received: teclistamab, elranatamab, idecabtagene vicleucel, and linvoseltamab. 
• Genomic findings at relapse: 
 - Acquired TNFRSF17 alterations were identified in all 5 patients. 
 - Alterations included extracellular-domain point mutations, focal monoallelic deletions, and complete biallelic TNFRSF17 loss in 1 patient. 
 - Mutations/indels clustered in exon 1, involving residues Y13, S30, P34, and C37, which are located in the extracellular domain relevant to antibody or CAR binding. 
 - In one patient, p.S30X and p.P34del were detected on separate sequencing reads, compatible with independent subclones, although a trans configuration within a shared subclone could not be excluded without single-cell DNA sequencing. 
    
• Treatment implications: 
 - In UPN4, no detectable BCMA alteration was found after idecabtagene vicleucel, supporting retreatment with a different BCMA-directed modality; linvoseltamab subsequently produced a VGPR. 
 - In UPN1, an acquired TNFRSF17 p.Y13N mutation after linvoseltamab exposure was followed by treatment with elranatamab, based on functional data showing preserved sensitivity; this produced a VGPR lasting 4 months. 
 - Subsequent progression in UPN1 coincided with biallelic TNFRSF17 deletion, consistent with complete BCMA antigen loss. 
    
• Additional genomic findings: At late relapse with biallelic TNFRSF17 loss, alterations involving CYLD, TRAF3, and TRAF2 were also observed, including three distinct CYLD mutations in UPN1 and biallelic TRAF3 deletion in UPN1 and a TRAF2 missense mutation in UPN3. 
    
• Patient characteristics: All 5 patients had high-risk cytogenetic profiles according to the cited International Myeloma Working Group/International Myeloma Society criteria. 
 
Limitations 
• Soluble BCMA levels were unavailable, preventing assessment of their correlation with TNFRSF17 genomic alterations and relapse dynamics. 
• The study was a 5-patient case series, and the authors state that prospective studies are needed to establish standardized resistance-guided treatment strategies. 
 
Why this study matters 
In this 5-patient case series, targeted TNFRSF17 sequencing at relapse identified acquired genetic alterations associated with resistance to BCMA-directed therapy, including extracellular-domain mutations and biallelic BCMA loss. The genomic findings directly informed treatment selection in 2 patients, while the absence of a detectable BCMA alteration supported sequential BCMA targeting in another patient. The authors conclude that BCMA sequencing should be considered at relapse after BCMA-directed therapy, while noting that prospective studies incorporating longitudinal genomic and functional analyses are needed to establish standardized treatment-selection strategies. 
 
Reference: 
Benjamin Podvin, Holly Lee, Rémi Tilmont, Gauthier Decool, Doriane Cavalieri, Hélène Demarquette, Nicolas Gower, Morgane Nudel, Emmanuelle Bourgeois, Daniela Robu, Sabine Tricot, Inès Arib, Victoria Cacheux, Aurélie Caillault-Venet, Claude Preudhomme, Nicolas Duployez, Thierry Facon, Paola Neri, Nizar Bahlis, Salomon Manier; TNFRSF17 genomic profiling guides retreatment with alternative BCMA-directed immunotherapies in multiple myeloma. Blood Adv 2026; 10 (17): 5934–5937. doi: https://doi.org/10.1182/bloodadvances.2026020518 

 
Routine Laboratory-Based Machine Learning for Discriminating Multiple Myeloma from Clinical Mimickers: Development and Internal Validation of a Diagnostic Prediction Model — Diagnostics (September 2026) 
 

What is the purpose of the study? 
To develop and internally validate statistical and machine-learning (ML) models that can distinguish multiple myeloma (MM) from clinically similar conditions using only routine demographic and laboratory parameters. The goal is to address potential diagnostic delays when specialized MM testing is not readily available. 
 
Summary 
This retrospective study included 422 consecutive patients referred to hematology for suspected MM at a tertiary care center from 2017–2025; 203 patients (48.1%) were diagnosed with MM. Using 15 routine variables, seven ML algorithms and two ensemble methods were evaluated, with Random Forest, Gradient Boosting, and Ensemble Stacking showing AUCs of 0.950–0.955 on the held-out test set; at a ≥95% sensitivity threshold, Random Forest had 77.3% specificity. Total protein, calcium, hemoglobin, and albumin were the strongest independent predictors, while Ensemble Stacking had the best calibration (Brier score 0.084; calibration slope 1.14). 
 
Key points 
• Study population: 422 patients referred to hematology for suspected MM; 203 (48.1%) had MM. 
• Model inputs: 15 routine demographic and laboratory variables; no myeloma-specific biomarkers, imaging findings, or clinical symptoms were included. 
• Model performance: 
 - Random Forest, Gradient Boosting, and Ensemble Stacking had test-set AUCs of 0.950–0.955. 
 - At ≥95% sensitivity, Random Forest maintained 77.3% specificity. 
 - Observed MM rates ranged from 2.4% in the very-low-risk group to 97.2% in the very-high-risk group. 
    
• Strongest predictors: Total protein (OR 11.95), calcium (OR 9.62), hemoglobin (OR 4.34), and albumin (OR 0.16). 
• Calibration: Ensemble Stacking had the best calibration, with a Brier score of 0.084 and calibration slope of 1.14. 
• Globulin gap: Alone, it had a test-set AUC of 0.769. Ensemble Stacking improved AUC by 0.194 versus the globulin gap (95% CI 0.111–0.281), while its improvement over standard logistic regression was smaller (ΔAUC 0.023). 
• Sensitivity analysis: After excluding calcium, creatinine, and hemoglobin, all models retained AUCs >0.93, with reductions of only 0.004–0.009. 
• Internal validation: Repeated 10-fold cross-validation and bootstrap optimism correction using 1,000 resamples supported the stability of the performance estimates. 
 
Limitations 
• Retrospective, single-center design, with potential selection and information bias and limited generalizability. 
• The cohort was a hematology referral population with a high MM prevalence (48.1%); performance and predictive values may differ in lower-prevalence settings. 
• The 70/30 random train–test split did not assess temporal changes in clinical practice or referral patterns. 
• Incorporation bias could not be excluded because the laboratory variables may have influenced the original referral decision. 
• External validation in independent cohorts was not performed. 
• Residual overfitting, particularly in tree-based models, could not be fully excluded. 
• The sample and test-set sizes may limit precision, and some estimates had wide confidence intervals. 
• Performance and fairness across demographic subgroups were not evaluated separately. 
• The models excluded myeloma-specific biomarkers, imaging, and symptoms, which may limit discrimination compared with more comprehensive diagnostic models. 
• The models provide information about MM diagnosis but not prognosis or staging. 
 
Why this study matters 
In this hematology referral cohort, ML models based exclusively on routine laboratory parameters showed high discrimination between MM and clinically similar conditions, with test-set AUCs above 0.95 for the best-performing models. The findings indicate potential utility for triage and prioritization of patients already being evaluated for suspected MM, but external validation and prospective evaluation are required before clinical implementation, and use in lower-prevalence settings would require recalibration and dedicated validation. 
 
Reference: 
Erdoğdu, B., Gül, D., Aylı, B. I., Karadeniz, M., Yıldırım, M., & Cömert, M. (2026). Routine Laboratory-Based Machine Learning for Discriminating Multiple Myeloma from Clinical Mimickers: Development and Internal Validation of a Diagnostic Prediction Model. Diagnostics, 16(18), 2928. https://doi.org/10.3390/diagnostics16182928 

Clinical Trials 
 

Blood-based MALDI-TOF mass spectrometry versus bone marrow MRD for monitoring multiple myeloma: CASSIOPEIA study results — Blood (August 2026) 
 

What is the purpose of the study? 
To evaluate whether serum mass spectrometry (MS) can provide prognostic information comparable to bone marrow minimal residual disease (MRD) testing in patients with multiple myeloma. Additionally, the study assesses whether serial serum MS could support non-invasive, phase-adapted MRD monitoring alongside bone marrow assessment. 
 
Summary 
This retrospective post-hoc analysis included 237 patients from the CASSIOPEIA trial and compared serum MS with bone marrow MRD assessed by next-generation flow cytometry (NGF) and next-generation sequencing (NGS) at predefined time points from post-induction through maintenance. At all assessed time points, MRD negativity by MS, NGF, or NGS was associated with longer progression-free survival (PFS), with comparable landmark prognostic performance across methods. Agreement between serum MS and bone marrow MRD improved during maintenance; serum MS showed high positive and negative predictive values relative to a 10⁻⁵ marrow reference, but had more limited rule-out performance compared with NGS at 10⁻⁶. 
 
Key points 
• Study population: 237 patients from the CASSIOPET companion study of the CASSIOPEIA trial; paired serum and bone marrow samples were prospectively collected at predefined time points. 
• Methods compared: Serum mass spectrometry (MS), bone marrow next-generation flow cytometry (NGF), and next-generation sequencing (NGS). 
• Prognostic value: MRD negativity by any of the three methods was associated with longer PFS at all assessed time points. 
• Method comparison: Landmark prognostic performance was comparable across platforms. 
• During maintenance: Agreement between serum MS and bone marrow MRD improved. 
• Reference sensitivity: Serum MS had high positive and negative predictive values relative to a 10⁻⁵ bone marrow MRD reference, but its ability to rule out disease was more limited when compared with NGS at 10⁻⁶. 
• Sustained MRD: Sustained MRD negativity for 1 or 2 years identified patients with favorable outcomes, irrespective of the assessment method. 
• Clinical role described by the study: The findings support using serum MS alongside, rather than in place of, bone marrow MRD assessment, particularly for more frequent non-invasive monitoring during maintenance. 
• Trial registration: CASSIOPEIA, ClinicalTrials.gov NCT02541383. 
 
Why this study matters 
Serum MS and bone marrow MRD demonstrated comparable prognostic value for PFS in this analysis of patients with multiple myeloma. The findings support a complementary, phase-adapted role for serial serum MS for non-invasive monitoring during maintenance, while bone marrow assessment remains part of evaluation when maximum sensitivity is required. 
 
Reference: 
Thomas Dejoie, Neila Rebouh, Jill Corre, Soraya Wuilleme, Françoise Kraeber-Bodere, Cyrille Hulin, Aurore Perrot, Cyrille Touzeau, Xavier P. Leleu, Bertrand Arnulf, Lionel Karlin, Philippe Moreau, Helene Caillon; Blood-based MALDI-TOF mass spectrometry versus bone marrow MRD for monitoring multiple myeloma: CASSIOPEIA study results. Blood 2026; blood.2026033773. doi: https://doi.org/10.1182/blood.2026033773 

Daratumumab plus bortezomib, lenalidomide, and dexamethasone in transplant-deferred newly diagnosed multiple myeloma: Frailty subgroup analysis of CEPHEUS — Leukemia (August 2026) 
 

What is the purpose of the study? 
To evaluate the efficacy, safety, and patient-reported outcomes of daratumumab, bortezomib, lenalidomide, and dexamethasone (DVRd) versus bortezomib, lenalidomide, and dexamethasone (VRd) in patients with newly diagnosed multiple myeloma (NDMM) who were transplant-ineligible or had transplantation deferred, across frailty subgroups defined by the International Myeloma Working Group (IMWG) and Intergroupe Francophone du Myélome (IFM) frailty indices. 
 
Summary 
CEPHEUS (NCT03652064) was a randomized, phase 3 trial in which 395 patients were assigned to DVRd (n=197) or VRd (n=198), with a median follow-up of 58.7 months. Across the evaluated frailty subgroups, MRD-negativity at ≥CR, sustained MRD-negativity, ≥CR rates, and progression-free survival (PFS) were higher with DVRd than VRd; the trial was not powered for overall survival, although a trend favored DVRd. Frailer patients had higher rates of grade 3/4 and serious treatment-emergent adverse events (TEAEs), particularly infections, while no detriment in health-related quality of life was observed across frailty subgroups. 
 
Key points 
• Population and design 
 - 395 patients with NDMM were randomized 1:1 to DVRd (n=197) or VRd (n=198). 
 - Median follow-up was 58.7 months (range, 0.1–64.7). 
 - Patients were transplant-ineligible or had transplantation deferred and had an ECOG performance status of 0–2. 
 - Patients with an IMWG frailty score ≥2 were excluded; therefore, patients classified as frail by IMWG criteria were not included. 
    
• Frailty classification 
 - By the IMWG index, 256 patients were fit and 139 were intermediate-fit. 
 - By the IFM simplified index, 297 patients were nonfrail and 98 were frail. 
 - 24.8% of patients had discordant frailty classifications between the IMWG and IFM approaches. 
 - Among IFM-defined frail patients, 85% were classified as intermediate-fit by IMWG. 
    
• Efficacy 
 - MRD-negativity at ≥CR was consistently higher with DVRd than VRd at both 10⁻⁵ and 10⁻⁶ thresholds across frailty subgroups. 
 - Results were also consistent for ≥12-month and ≥24-month sustained MRD-negativity. 
 - PFS and ≥CR rates were higher with DVRd than VRd across all evaluated frailty subgroups. 
 - CEPHEUS was not powered for overall survival; a trend favored DVRd across subgroups. 
 - The treatment effect of DVRd strengthened in all subgroups when deaths related to COVID-19 were censored. 
    
• Safety and quality of life 
 - Grade 3/4 and serious TEAEs were more frequent in frailer subgroups in both treatment arms. 
 - Serious infections were mainly pneumonia or COVID-19. 
 - Serious infection rates in the IMWG intermediate-fit subgroup were 46.6% with DVRd and 41.3% with VRd; in the IFM frail subgroup, they were 47.4% and 53.8%, respectively. 
 - Treatment discontinuation of all study drugs because of TEAEs was lower with DVRd than VRd across frailty subgroups. 
 - Bortezomib discontinuation due to TEAEs was lower with DVRd in the frailer subgroups, and discontinuation because of peripheral sensory neuropathy was lower with DVRd across frailty subgroups. 
 - No detriment in health-related quality of life was observed across frailty subgroups. 
 
Strengths 
The analysis was conducted within the randomized, phase 3 CEPHEUS trial and assessed efficacy, safety, and patient-reported outcomes by treatment and frailty status. 
 
Limitations  
• CEPHEUS excluded patients who were frail according to IMWG criteria and patients aged >80 years, so the efficacy and feasibility of DVRd in patients meeting IMWG frailty criteria remain to be established. 
• The authors state that the IFM index may overestimate frailty, and discordance between IMWG and IFM classifications occurred in 24.8% of patients. 
• The authors state that additional prospective studies are warranted. 
 
Why this study matters 
In this CEPHEUS analysis, DVRd showed clinical benefit compared with VRd across the evaluated frailty subgroups, including higher MRD-negativity and ≥CR rates and improved PFS. Frailer patients had higher rates of grade 3/4 and serious TEAEs, particularly infections, but no detriment in health-related quality of life was observed; because patients who were IMWG-frail and those aged >80 years were excluded, the efficacy and feasibility of DVRd in these populations remain to be established. The findings, together with previously reported DRd results in frailty subgroups, were described by the authors as informing daratumumab regimen selection for patients with NDMM who do not receive frontline transplant, with treatment tailored according to patient fitness, bortezomib eligibility, treatment goals, and treatment access. 
 
Reference: 
Zweegman, S., Usmani, S.Z., Hungria, V. et al. Daratumumab plus bortezomib, lenalidomide, and dexamethasone in transplant-deferred newly diagnosed multiple myeloma: Frailty subgroup analysis of CEPHEUS. Leukemia (2026). https://doi.org/10.1038/s41375-026-03111-0 
 
 

Daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis — Leukemia (August 2026) 
 

What is the purpose of the study? 
To evaluate whether adding daratumumab to lenalidomide/dexamethasone (D-Rd) improves long-term overall survival (OS) and delays the need for subsequent antimyeloma treatment compared with lenalidomide/dexamethasone (Rd) in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). 
 
Summary 
In the final analysis of the MAIA study, 737 patients were randomized to D-Rd (n=368) or Rd (n=369), with a median follow-up of 89.3 months (7.4 years), median OS was 90.3 months with D-Rd versus 64.1 months with Rd (HR 0.67; 95% CI, 0.55–0.82), and estimated 7-year OS was 53.1% versus 39.3%, respectively. Median time to subsequent antimyeloma treatment was not reached with D-Rd versus 42.4 months with Rd (HR 0.51; 95% CI, 0.41–0.63; P<0.0001). Death due to adverse events occurred in 12% of patients receiving D-Rd and 11% receiving Rd. 
 
Key points 
• Population: 737 patients with transplant-ineligible NDMM were randomized to D-Rd or Rd. 
• Follow-up: Median 89.3 months (range, 0.0–102.2 months). 
• Overall survival: 
 - D-Rd: 90.3 months (7.5 years); 95% CI, 80.8–NE. 
 - Rd: 64.1 months (5.3 years); 95% CI, 56.0–70.8. 
 - HR for death: 0.67 (95% CI, 0.55–0.82). 
 - Estimated 7-year OS: 53.1% with D-Rd versus 39.3% with Rd. 
    
• Subsequent antimyeloma treatment: 
 - 38% of D-Rd patients versus 55% of Rd patients received at least one subsequent antimyeloma therapy. 
 - Median time to subsequent treatment was not reached with D-Rd versus 42.4 months with Rd (HR, 0.51; 95% CI, 0.41–0.63; P<0.0001). 
 - 29% of patients initially treated with Rd received a subsequent daratumumab-based regimen, compared with 6% of those initially treated with D-Rd. 
    
• Safety/deaths: Deaths primarily attributed to adverse events occurred in 44/364 (12%) patients in the D-Rd group and 40/365 (11%) in the Rd group. No new safety concerns related to death were identified in the final analysis. 
• Subgroups: The OS benefit generally remained consistent across prespecified subgroups, including age groups and patients with high cytogenetic risk. 
• MRD: Rates of MRD negativity and sustained MRD negativity of at least 12 months were higher with D-Rd; however, no additional MRD data were collected after the previous analysis. 
• Subsequent therapies: Treatment choices were affected by differences in regimen approvals and reimbursement across countries and study periods. No patients received BCMA- or GPRC5D-targeted therapy, and only two patients in each group received investigational drugs in subsequent lines. 
 
Strengths
The study provides long-term OS follow-up of more than 7 years from the MAIA trial and includes analyses of subsequent antimyeloma therapies. 
 
Limitations
• The study was open-label, which might have introduced bias toward earlier withdrawal in the Rd group. 
• Some prespecified OS subgroups had small sample sizes, limiting interpretation of those subgroup results. 
• After the protocol amendment, updated efficacy data beyond survival and adverse-event data were not collected; missing data were also identified as a limitation. 
• Safety data in the final analysis were limited to death-related data, rather than comprehensive adverse-event collection. 
• Differences in subsequent-treatment approvals and reimbursement across countries may have affected subsequent therapy choices and OS. 
 
Why this study matters 
At a median follow-up of approximately 7.5 years, the MAIA final analysis found median OS of 90.3 months with D-Rd versus 64.1 months with Rd in transplant-ineligible patients with NDMM, with an OS hazard ratio of 0.67 (95% CI, 0.55–0.82). D-Rd was also associated with a longer time to subsequent antimyeloma treatment, while the final analysis identified no new death-related safety concerns; interpretation is subject to the study's stated limitations, including its open-label design, limited subgroup sizes, and restricted safety data collection. 
 
Reference: 
Facon, T., Kumar, S.K., Orlowski, R.Z. et al. Daratumumab, lenalidomide, and dexamethasone in transplant-ineligible newly diagnosed multiple myeloma: MAIA final survival analysis. Leukemia (2026). https://doi.org/10.1038/s41375-026-03097-9 

BiRD Regimen Followed by Anti-BCMA CAR-T Cell Immunotherapy as First-Line Therapy for Newly Diagnosed Multiple Myeloma: A Prospective, Single-Arm, Phase 2 Trial — American Journal of Hematology (August 2026) 
 

What is the purpose of the study? 
To evaluate the preliminary efficacy, safety, and quality of life (QoL) of first-line BiRD (clarithromycin, lenalidomide, and dexamethasone) followed by BCMA CAR-T cell therapy, with or without subsequent autologous stem cell transplantation (ASCT), in patients with newly diagnosed multiple myeloma (NDMM). The treatment strategy was designed to reduce tumor burden with BiRD and subsequently achieve deep remission, including MRD-negative CR, while assessing safety and QoL. 
 
Summary 
This prospective study enrolled 18 patients with NDMM at the First Affiliated Hospital of Soochow University from October 2017 to November 2023. Patients received a median of 2 cycles of BiRD, followed by BCMA CAR-T cell infusion; 12 subsequently underwent ASCT, and lenalidomide maintenance was administered after CAR-T therapy or ASCT. After BiRD, the overall response rate (ORR) was 100%; after BCMA CAR-T therapy, 14/18 (77.8%) achieved stringent CR (sCR) and MRD-negative CR, 1/18 (5.6%) achieved CR, and 3/18 (16.7%) achieved VGPR. 
 
With a median follow-up of 22.5 months (range, 5.8–76.8 months), one patient relapsed and one patient died of COVID-19. The estimated 3-year OS and PFS were both 100%, while estimated 5-year OS was 80.00% ± 17.89% and PFS was 75.00% ± 21.65%; median OS, PFS, and DOR were not reached. Grade 1–2 cytokine release syndrome (CRS) occurred in 17/18 (94%) patients, with no grade ≥3 CRS or ICANS; grade III–IV neutropenia, anemia, and thrombocytopenia occurred in 94%, 39%, and 61%, respectively, and improvement was observed in most assessed QoL domains after BCMA CAR-T therapy. 
 
Key points 
• Clinical Trial NCT04287660 
• Population: 18 patients with NDMM; median age 58 years (range, 43–69). 
• Disease risk: 8 patients were classified as high-risk according to mSMART 3.0; 4 of these 8 were double-hit. 
• Induction: BiRD for a median of 2 cycles (range, 1–4). 
• Response after BiRD: 100% ORR 
 - CR: 2/18 (11.1%) 
 - VGPR: 11/18 (61.1%) 
 - PR: 5/18 (27.8%) 
    
• Response after BCMA CAR-T: 
 - sCR and MRD-negative CR: 14/18 (77.8%) 
 - CR: 1/18 (5.6%) 
 - VGPR: 3/18 (16.7%) 
 - All patients achieved at least VGPR
    
• ASCT: 12 patients underwent ASCT 3.8–8.7 months after CAR-T infusion. Three patients did not undergo ASCT, while three had recently completed BCMA CAR-T therapy at the time of reporting. 
• Follow-up: Median 22.5 months (range, 5.8–76.8 months). 

• Disease outcomes: 
 - 1 patient relapsed 18 months after ASCT
 - 1 patient died of COVID-19 33 months after ASCT
 - Estimated 3-year OS: 100% 
 - Estimated 3-year PFS: 100% 
 - Estimated 5-year OS: 80.00% ± 17.89% 
 - Estimated 5-year PFS: 75.00% ± 21.65% 
 - Estimated 3-year and 5-year CIR: 11.11% ± 10.47% 
 - Median OS, PFS, and DOR were not reached. 
    
• Safety after BiRD: Thromboembolic events occurred in 16.7%, pulmonary infection in 5.6%, and significant fatigue in 5.6%; these events resolved. No neurotoxicity was reported. 
• Safety after CAR-T: Grade 1–2 CRS occurred in 94% (17/18); no patient experienced grade ≥3 CRS, and no ICANS was observed. 
• Hematologic toxicity: Grade III–IV neutropenia, anemia, and thrombocytopenia occurred in 94%, 39%, and 61%, respectively. The reported adverse events recovered. 
• QoL: Improvement was observed in most QLQ-C30 and QLQ-MY20 domains from baseline to after BCMA CAR-T therapy, particularly in pain and disease symptoms. 
• Limitation: The authors state that the small sample size requires further validation in a larger study, particularly for conclusions regarding the role of ASCT after BCMA CAR-T therapy. 
• Study characteristic: The study was prospective and evaluated efficacy, safety, and QoL in the first-line setting for NDMM. 
 
Why this study matters 
In this prospective study of 18 patients with NDMM, the ORR after BiRD was 100%, and after BCMA CAR-T therapy, 77.8% (14/18) achieved sCR and MRD-negative CR. At a median follow-up of 22.5 months, one relapse and one COVID-19-related death were reported; estimated 3-year OS and PFS were both 100%, while grade 1–2 CRS and hematologic toxicities were the main reported adverse events, with no grade ≥3 CRS or ICANS. The authors reported improvement in most assessed QoL domains and noted that the small sample size requires larger studies to further evaluate the treatment strategy, including the role of ASCT after BCMA CAR-T therapy. 
 
Reference: 
Y. Zhou, J. Chen, Q. Cui, et al., “BiRD Regimen Followed by Anti-BCMA CAR-T Cell Immunotherapy as First-Line Therapy for Newly Diagnosed Multiple Myeloma: A Prospective, Single-Arm, Phase 2 Trial,” American Journal of Hematology (2026): 1–6, https://doi.org/10.1002/ajh.70485. 

Autologous Chimeric Antigen Receptor (CAR) T-cells Targeting the Kappa Myeloma Antigen (KMA) in Kappa Restricted Multiple Myeloma Patients With Relapsed/ Refractory Disease (KOALA) — HaemaLogiX Ltd (August 2026) 
 

What is the purpose of the study? 
The Phase 1 KOALA trial (NCT07541391) is evaluating the safety and preliminary efficacy of KMCAR™ T-cell therapy (PMCC-COE-KMA) in patients with relapsed/refractory kappa-restricted multiple myeloma who are no longer responding to standard treatments and are not eligible for other CAR-T therapies. The dose-escalation study is also assessing how patients tolerate different dose levels of this first-in-human KMCAR™ T-cell therapy. 
 
Summary 
The first patient in the KOALA trial was treated with KMCAR™ T-cell therapy and, according to the study announcement, experienced no serious adverse events and was considered to have tolerated the treatment. A second patient has been enrolled and is scheduled to receive a higher dose level. KMCAR™ T-cells are genetically modified from a patient's own T cells to recognize the Kappa Myeloma Antigen (KMA), a receptor described as being present on kappa-type malignant plasma cells and absent from healthy immune cells. 
 
Key points 
• Trial: Phase 1 KOALA study, ClinicalTrials.gov identifier NCT07541391. 
• Study site: Peter MacCallum Cancer Centre's Centre of Excellence in Cellular Immunotherapy. 
• Population: Patients with relapsed/refractory multiple myeloma who no longer respond to standard treatment options and are not eligible for other CAR-T therapies. 
• Treatment: KMCAR™ T-cell therapy (PMCC-COE-KMA), a first-in-human T-cell immunotherapy. 
• Target: Kappa Myeloma Antigen (KMA), described in the study announcement as a tumour-specific receptor on kappa-type myeloma cells and absent from healthy immune cells. 
• Initial treatment: The first patient was treated and reported to have no serious adverse events and to have tolerated the treatment. 
• Next patient: A second patient has been enrolled and is scheduled to receive a higher dose level. 
• Treatment process: A patient's own T cells are collected, genetically modified to produce KMCAR™ T-cells, and then infused back into the patient. 
• Study objective: The dose-escalation trial assesses safety and preliminary efficacy. 
• Strengths explicitly described: The study is a first-in-human clinical evaluation and uses a dose-escalation design to assess safety across dose levels. 
• Limitations explicitly described: The announcement does not explicitly state study limitations; therefore, none are added here. 
 
Why this study matters 
The KOALA Phase 1 trial has treated its first patient with KMCAR™ T-cell therapy, with no serious adverse events reported after the initial infusion and the treatment described as well tolerated. The trial is continuing with a second patient scheduled for treatment at a higher dose level while evaluating the therapy's safety and preliminary efficacy in relapsed/refractory kappa-restricted multiple myeloma. 
 
Reference: 
HaemaLogiX Announces Major Milestone with First Patient Successfully Dosed with KMCAR™ T-Cell. HaemaLogiX press release. August 26, 2026. 

 
Clinical features and management of GPRC5D-associated adverse events in novel GPRC5D × CD3 bispecific talquetamab-treated relapsed/refractory multiple myeloma patients: the MonumenTAL-1 China cohort experience — Hematology (September 2026) 
 

What is the purpose of the study? 
To evaluate the safety profile of talquetamab, a G-protein–coupled receptor class C group 5 member D (GPRC5D) × CD3 bispecific antibody, in Chinese adults with heavily pretreated relapsed/recurrent multiple myeloma (RRMM), with particular focus on GPRC5D-associated on-target/off-tumor adverse events (AEs). It assessed the incidence, time to onset, duration, recovery, and management of these AEs in the China cohort of the phase I/II MonumenTAL-1 study. 
 
Summary 
This post-hoc analysis included 41 Chinese patients with RRMM: 29 received subcutaneous talquetamab 0.4 mg/kg once weekly (QW) and 12 received 0.8 mg/kg every 2 weeks (Q2W). Median treatment duration was 7.7 months and 7.1 months, respectively, with median follow-up of 16.3 and 13.9 months. GPRC5D-associated AEs were predominantly grade 1–2 and most commonly involved the mouth (dysgeusia and dry mouth), skin (rash and non-rash skin toxicity), and nails; 50%–100% had resolved by the respective data cutoffs, and supportive treatments were used for management. One grade 3 non-rash skin toxicity occurred in the QW cohort, and talquetamab dose modification was required in one patient for grade 2 weight decrease. 
 
Key points 
• Study population: 41 adult Chinese patients with heavily pretreated RRMM; 29 in the QW cohort and 12 in the Q2W cohort. 
• Treatment: Subcutaneous talquetamab 0.4 mg/kg QW or 0.8 mg/kg Q2W, with step-up dosing and prophylactic treatment to mitigate cytokine release syndrome (CRS). 
• Most common GPRC5D-associated AEs: 
 - Oral: dysgeusia, dry mouth 
 - Skin: rash, non-rash skin toxicity 
 - Nail: nail disorders 
    
• Severity: AEs were predominantly grade 1–2. One grade 3 non-rash skin toxicity was reported in the QW cohort. 
• Recovery: 50%–100% of GPRC5D-associated AEs had resolved by the applicable data cutoff. 
• Dose modification: Required in one case, for grade 2 weight decrease; GPRC5D-associated AEs rarely led to dose modification or discontinuation. 
• Efficacy data reported in the discussion: Objective response rates were 69.0% in the QW cohort and 66.7% in the Q2W cohort; the authors noted that detailed long-term efficacy findings were planned for a separate publication. 
• Comparison with the global MonumenTAL-1 population: Dysgeusia occurred in 36.6% of the Chinese patients versus 72% globally, and nail toxicity in 19.5% versus 54.2%, respectively. The authors stated that further investigation is warranted to understand population-specific safety profiles. 
• Management: GPRC5D-associated AEs were generally managed with supportive therapies and standard treatments, allowing patients to remain on treatment in most cases. 
• Limitations: The authors identified the relatively small number of patients, short follow-up, and descriptive nature of the analyses as limitations that restrict interpretation and comparisons with other studies. They also noted that AE-management approaches included local practices in addition to standardized protocols. 
• Further research: The authors stated that larger patient samples are needed to confirm the findings. 
 
Why this study matters 
In this Chinese cohort of heavily pretreated patients with RRMM, GPRC5D-associated AEs during talquetamab treatment were predominantly mild, with 50%–100% resolving by the relevant data cutoffs and very few requiring dose modification. The authors reported that the findings were consistent with the known safety profile of talquetamab in the global MonumenTAL-1 population and emphasized patient education and timely management of these AEs before and during treatment. 
 
 
Reference: 
An, G., Jin, J., Cai, Z., Jing, H., Fu, C., He, P., … Qiu, L. (2026). Clinical features and management of GPRC5D-associated adverse events in novel GPRC5D × CD3 bispecific talquetamab-treated relapsed/refractory multiple myeloma patients: the MonumenTAL-1 China cohort experience. Hematology, 31(1). https://doi.org/10.1080/16078454.2026.2702681 
 

Teclistamab and Daratumumab Immune-Based Doublet Therapy for Relapsed/Refractory Multiple Myeloma: the TRIMM-2 Study — Blood Advances (September 2026) 
 

What is the purpose of the study? 
To evaluate the safety and efficacy of weight-based teclistamab combined with daratumumab in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). The primary endpoint is safety, while secondary endpoints include overall response rate (ORR) and duration of response (DOR), with progression-free survival (PFS) assessed as an exploratory endpoint. 
 
Summary 
In the phase 1b TRIMM-2 study (NCT04108195), 61 patients received weight-based recommended phase 2 doses (RP2D) of subcutaneous teclistamab (1.5 mg/kg once weekly or 3.0 mg/kg every 2 weeks) plus subcutaneous daratumumab; the median number of prior lines of therapy was 5 (range, 1–14), and median follow-up was 12.0 months. The ORR was 68.9%, including 44.3% with complete response or better, median DOR was not reached, and median PFS was 26.3 months. The most common treatment-emergent adverse events (TEAEs) were infections, cytokine release syndrome, neutropenia, and anemia; grade 3/4 TEAEs occurred in 93.4% of patients, 7 patients died from TEAEs, and no dose-limiting toxicities occurred. 
 
Key points 
• Treatment: Weight-based teclistamab plus daratumumab in patients with RRMM who had received ≥3 prior lines of therapy or were double-refractory to a proteasome inhibitor and immunomodulatory drug. 
• Prior treatment: Median 5 prior lines of therapy (range, 1–14); prior anti-CD38 treatment was permitted. 
• Response: ORR was 68.9%; 44.3% achieved a complete response or better. 
• Duration of response: Median DOR was not reached at the reported follow-up. 
• Progression-free survival: Median PFS was 26.3 months. 
• Safety: Common TEAEs included infections, cytokine release syndrome, neutropenia, and anemia. 
• Serious safety findings: Grade 3/4 TEAEs occurred in 93.4% of patients, and 7 patients died from TEAEs; no dose-limiting toxicities occurred. 
• Fixed-dose cohort: The fixed-dose teclistamab cohort (100–300 mg) was stopped early after a safety signal involving fatal infections; patients were switched to weight-based dosing as a precaution. 
• Infection management: The study findings emphasized infection monitoring, prophylaxis, and early immunoglobulin replacement. 
 
Strengths 
The study explicitly describes a well-characterized safety profile and reports both response and PFS outcomes in this patient population. 
 
Why this study matters 
In the TRIMM-2 study, weight-based RP2D teclistamab combined with daratumumab produced an ORR of 68.9% and a median PFS of 26.3 months in patients with heavily pretreated RRMM, while median DOR was not reached at a median follow-up of 12.0 months. Safety findings included frequent infections and other treatment-emergent adverse events, including grade 3/4 events and treatment-emergent deaths, supporting the study's stated emphasis on infection monitoring, prophylaxis, and early immunoglobulin replacement. 
 
Reference: 
Paula Rodriguez-Otero, Daniel Morillo, Anita D'Souza, Donna Reece, Niels van de Donk, Ajai Chari, Bhagirathbhai Dholaria, K. Martin Kortüm, Maria-Victoria Mateos, John T. Mckay, Laura Rosiñol, Anna Sureda, Ralph Wäsch, Manisha Bhutani, Katja C Weisel, Nizar J Bahlis, Deeksha Vishwamitra, Sheri Skerget, Kalpana K Bakshi, Yue Guo, Weili Sun, Jenna D. Goldberg, Tara Stephenson, Thomas J Prior, Lien Vandenberk, Sangmin Lee, M. Damiette Smit, Raluca I. Verona, Albert Oriol, Amrita Krishnan; Teclistamab and Daratumumab Immune-Based Doublet Therapy for Relapsed/Refractory Multiple Myeloma: the TRIMM-2 Study. Blood Adv 2026; bloodadvances.2026020648. doi: https://doi.org/10.1182/bloodadvances.2026020648 

Patient-Reported Outcomes and Healthcare Provider Perspectives on Subcutaneous Isatuximab Delivery via On-Body Injector vs Manual Injection: Results From the Phase 2 IZALCO Study in Relapsed/Refractory Multiple Myeloma — Clinical Lymphoma Myeloma and Leukemia (September 2026) 
 

What is the purpose of the study? 
To evaluate patient-reported outcomes and healthcare provider (HCP) experiences with subcutaneous (SC) isatuximab administered by an on-body injector (Isa SC OBI) compared with manual injection, in combination with carfilzomib-dexamethasone, in adults with relapsed/refractory multiple myeloma. 
 
Summary 
The phase 2 IZALCO study (NCT05704049) included 74 adults and 19 HCPs. In part 2, patients received both administration methods during cycles 1–6 and, at cycle 6 Day 15, 35/47 patients (74.5%) preferred Isa SC OBI, mainly citing comfort, convenience, and reduced injection-site pain; 47/52 patients (90.4%) subsequently chose Isa SC OBI from cycle 7 onward. Fewer patients reported discomfort, pain, and side effects with Isa SC OBI at most assessed time points, while mean EORTC QLQ-C30 global health status/quality-of-life scores were maintained over time; 15/19 HCPs (78.9%) preferred Isa SC OBI. 
 
Key points 
• Study: Phase 2 IZALCO study (NCT05704049). 
• Participants: 74 adults with relapsed/refractory multiple myeloma and 19 HCPs. 
• Treatment: SC isatuximab with carfilzomib-dexamethasone, administered by manual injection or Isa SC OBI. 
• Patient preference: At cycle 6 Day 15, after experiencing both methods, 74.5% (35/47) preferred Isa SC OBI. 
• Reasons for preference: Comfort, convenience, and reduced injection-site pain. 
• Patient experience: Fewer patients reported discomfort, pain, and side effects with Isa SC OBI at most time points. 
• Later treatment choice: 90.4% (47/52) of patients selected Isa SC OBI from cycle 7 onward. 
• Quality of life: Mean EORTC QLQ-C30 global health status/quality-of-life score was maintained over time. 
• HCP preference: 78.9% (15/19) of HCPs preferred Isa SC OBI. 
 
Strengths 
The study assessed patient-reported outcomes and HCP experiences, and patients in part 2 experienced both administration methods before reporting their preference. 
 
Why this study matters 
After experiencing both administration methods, most evaluated patients preferred Isa SC OBI to manual injection, with comfort, convenience, and reduced injection-site pain reported as the main reasons. Most patients subsequently selected Isa SC OBI when given a choice, and 78.9% of participating HCPs also preferred it; mean EORTC QLQ-C30 global health status/quality-of-life scores were maintained over time. 
 
Reference: 
Gurdeep Parmar, Marcelo Capra, Vania Hungria, Fernanda Salles Seguro, Meletios-Athanasios Dimopoulos, Sosana Delimpasi, Ivan Špička, Jiří Minařík, Herlander Marques, Ludĕk Pour, Jana Mihályová, Junichiro Yuda, Kazutaka Sunami, Graça Esteves, Cynthia Chmielewski, Christine Soufflet, Disa Yu, Erin Comerford, Florence Suzan, Paul Cordero, Rick Zhang, Hang Quach, Patient-Reported Outcomes and Healthcare Provider Perspectives on Subcutaneous Isatuximab Delivery via On-Body Injector vs Manual Injection: Results From the Phase 2 IZALCO Study in Relapsed/Refractory Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.08.019.  
 
 

Phase 3 CERVINO Trial: Positive Topline Results Show Etentamig Significantly Improved Response Rate and Progression-Free Survival in Relapsed/Refractory Myeloma — AbbVie (September 2026) 
 

What is the purpose of the study? 
To evaluate whether etentamig, an investigational BCMA × CD3 bispecific T-cell engager, improves treatment outcomes compared with investigators’ choice of standard available therapies (SAT) in patients with triple-class exposed relapsed/refractory multiple myeloma (RRMM). The study assesses objective response rate (ORR) and progression-free survival (PFS) as its dual primary endpoints. 
 
Summary 
The Phase 3 CERVINO trial is a global, randomized, open-label Phase 3 study involving 393 patients with RRMM who had received at least two prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody; patients received etentamig once every four weeks (Q4W) or investigator’s choice of SAT. At a median follow-up of 11.4 months, etentamig produced a higher ORR than SAT (74.0% vs. 45.7%; P<0.0001) and improved PFS (HR 0.40; 95% CI, 0.29–0.54; P<0.0001); 12-month overall survival (OS) was 87.9% vs. 72.0%, although the prespecified OS efficacy boundary was not crossed at the data cutoff. 
 
Etentamig was administered with a single step-up dose followed by monthly Q4W dosing from initiation; among patients receiving the single step-up dose, cytokine release syndrome (CRS) occurred in 28.3%, predominantly grade 1 (23.9%), with no grade ≥3 CRS, while grade 3/4 infections occurred in 27.7% of etentamig-treated patients versus 19.2% with SAT, and grade 5 infections occurred in 1.5% vs. 3.1%, respectively. 
 
Key points 
• Study: Phase 3 CERVINO (NCT06158841), randomized, open-label, multicenter study. 
• Population: 393 patients with RRMM who were triple-class exposed and had received a median of 3 prior lines of therapy. 
• Treatment: Etentamig Q4W after a single step-up dose versus investigator’s choice of SAT. 
• Primary endpoints: ORR and PFS. 
• ORR: 74.0% with etentamig vs. 45.7% with SAT (P<0.0001). 
• PFS: Etentamig was associated with a PFS hazard ratio of 0.40 (95% CI, 0.29–0.54; P<0.0001). 
• Overall survival: 12-month OS was 87.9% with etentamig vs. 72.0% with SAT (HR, 0.48; 95% CI, 0.29–0.77; nominal P=0.0012). The prespecified OS efficacy boundary was not crossed at the data cutoff. 
• CRS: Among patients receiving a single step-up dose, CRS occurred in 28.3%, with 23.9% grade 1 and no grade ≥3 events reported. 
• ICANS: One patient (0.9%) experienced grade 1 ICANS; no grade ≥2 events were reported. 
• Infections: Grade 3/4 infections occurred in 27.7% with etentamig vs. 19.2% with SAT; grade 5 infections occurred in 1.5% vs. 3.1%. 
• Treatment discontinuation: Treatment-emergent adverse-event-related discontinuations were 3.6% with etentamig vs. 9.6% with SAT. 
• Interim analysis: This was the first planned efficacy interim analysis; following the observed benefit, the Independent Data Monitoring Committee recommended unblinding. 
 
Strengths 
The study was global, randomized, multicenter, Phase 3, and evaluated dual primary endpoints of ORR and PFS with prespecified subgroup analyses. 
 
Why this study matters 
In the CERVINO study, etentamig demonstrated a higher ORR and longer PFS than investigators’ choice of SAT in patients with triple-class exposed RRMM, with ORR of 74.0% vs. 45.7% and a PFS hazard ratio of 0.40 at a median follow-up of 11.4 months. With a single step-up dose followed by Q4W dosing, CRS was predominantly grade 1 and no grade ≥3 CRS was reported among patients receiving the single step-up dose; however, grade 3/4 infections were more frequent with etentamig than SAT, and the prespecified OS efficacy boundary had not been crossed at the data cutoff. 
 
Reference: 
AbbVie Announces Positive Topline Results from the Phase 3 CERVINO Trial Showing Etentamig Significantly Improved Response Rate and Progression-Free Survival in Patients with Relapsed/Refractory Multiple Myeloma. Abbvie press release. September 3, 2026. 
 
 

Induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in patients with high-risk multiple myeloma (OPTIMUM/MUKnine): 5-year follow-up of a multicentre, externally controlled, phase 2 trial — The Lancet Oncology (September 2026) 
 

What is the purpose of the study? 
To evaluate whether intensified induction, extended consolidation, and daratumumab–lenalidomide maintenance after autologous stem-cell transplantation (ASCT) could improve long-term outcomes in patients with newly diagnosed high-risk multiple myeloma or plasma cell leukemia. 
 
Summary 
In the OPTIMUM/MUKnineb multicentre, phase 2 trial, 107 patients with high-risk multiple myeloma received a risk-stratified treatment regimen including daratumumab, bortezomib, lenalidomide, cyclophosphamide, dexamethasone, ASCT with melphalan–bortezomib, extended consolidation, and daratumumab–lenalidomide maintenance; outcomes were compared with 120 genetically matched patients from the Myeloma XI trial. At a median follow-up of 71.1 months, median progression-free survival and overall survival had not been reached with OPTIMUM/MUKnine versus 24.4 months and 57.4 months, respectively, with Myeloma XI; progression-free survival 2 was also not reached versus 43.9 months. 
 
Key points 
• Study design: Multicentre, externally controlled, phase 2 OPTIMUM/MUKnineb trial conducted at 22 UK centres. 
• Clinical Trial: NCT03188172  
• Participants: 108 patients with high-risk multiple myeloma were recruited; 107 were included in the analysis, alongside 120 genetically matched patients from Myeloma XI. 
• Follow-up: Median follow-up was 71.1 months for OPTIMUM/MUKnineb and 117.8 months for Myeloma XI. 
• Progression-free survival: Median was not reached (NR) with OPTIMUM/MUKnineb versus 24.4 months with Myeloma XI (HR 0.32, 95% CI 0.22–0.45; p<0.0001). 
• Overall survival: Median was not reached with OPTIMUM/MUKnineb versus 57.4 months with Myeloma XI (HR 0.43, 95% CI 0.28–0.65; p<0.0001). 
• Progression-free survival 2: Median was not reached with OPTIMUM/MUKnineb versus 43.9 months with Myeloma XI (HR 0.26, 95% CI 0.17–0.41; p<0.0001). 
• Molecular subgroups: The survival benefit was consistent across the reported high-risk multiple myeloma subgroups except in patients with three or more high-risk cytogenetic abnormalities (HRCAs). 
 
Why this study matters 
At 5-year follow-up, the OPTIMUM/MUKnine treatment strategy was associated with longer progression-free survival, progression-free survival 2, and overall survival than the genetically matched Myeloma XI external control cohort in patients with newly diagnosed high-risk multiple myeloma. The reported survival benefit was consistent across the specified molecular subgroups except for patients with three or more HRCAs. 
 
 
Reference: 
Kaiser MF, Phillip RH, Brown SR, Holroyd A, Ferris E, de Tute RM, Roberts S, Clayton L, Bowles K, Garg M, Lokare A, Messiou C, Houlston RS, Jackson G, Cook G, Owen RG, Drayson MT, Pratt G, Hall A, Jenner MW. Induction and extended consolidation with daratumumab, cyclophosphamide, bortezomib, lenalidomide, and dexamethasone in patients with high-risk multiple myeloma (OPTIMUM/MUKnine): 5-year follow-up of a multicentre, externally controlled, phase 2 trial. Lancet Oncol. 2026 Sep 7:S1470-2045(26)00286-X. doi: 10.1016/S1470-2045(26)00286-X. Epub ahead of print. 
 
 

Phase 2 QUINTESSENTIAL Trial Results: Arlo-cel Showed Significant Overall Response Rate in RRMM — Bristol Myers Squibb (September 2026) 
 

What is the purpose of the study? 
To evaluate the efficacy and safety of arlocabtagene autoleucel (arlo-cel; BMS-986393), an autologous GPRC5D-directed CAR T-cell therapy, in adults with quadruple-class exposed relapsed and refractory multiple myeloma (RRMM), including patients previously treated with BCMA-targeted therapies. 
 
Summary 
The QUINTESSENTIAL trial (NCT06297226) is a Phase 2, open-label, multicenter, single-arm registrational study in patients with quadruple-class exposed RRMM, defined as prior treatment with an immunomodulatory drug (IMiD), proteasome inhibitor (PI), anti-CD38 therapy, and BCMA-targeted therapy; some participants had also received prior CAR T-cell therapy. The study met its primary endpoint of overall response rate (ORR) in patients who had received ≥4 prior lines of therapy and its key secondary endpoint of complete response rate (CRR) in this population, as well as the ORR and CRR endpoints in patients who had received ≥3 prior lines of therapy; the reported safety profile was consistent with that of other CAR T-cell therapies and GPRC5D-targeting therapies in multiple myeloma. 
 
Key points 
• Phase/design: Phase 2, open-label, multicenter, single-arm, registrational study. 
• Population: Adults with quadruple-class exposed relapsed and refractory multiple myeloma (RRMM). 
• Quadruple-class exposure: Prior treatment with an IMiD, PI, anti-CD38 therapy, and BCMA-targeted therapy. 
• Prior CAR T-cell therapy: The trial included patients who had previously received CAR T-cell therapies. 
• Investigational therapy: Arlocabtagene autoleucel (arlo-cel; BMS-986393), an autologous GPRC5D-directed CAR T-cell therapy. 
• Primary endpoint: ORR, defined as a best overall response of partial response (PR) or better, among quadruple-class exposed patients with ≥4 prior lines of therapy. 
• Reported efficacy: The primary ORR endpoint was met with a statistically significant result; the study also met the specified CRR endpoint in patients with ≥4 prior lines and the ORR and CRR endpoints in patients with ≥3 prior lines. 
• Safety: The reported safety profile was described as consistent with other CAR T-cell therapies and other GPRC5D-targeting therapies in multiple myeloma. 
• Study limitation explicitly identifiable from the provided text: The study was single-arm and open-label; no randomized comparator group is described in the provided study information. 
• Important data not provided: The announcement does not provide the numerical ORR, CRR, statistical estimates, confidence intervals, duration of response, or detailed adverse-event rates in the supplied text. 
 
Why this study matters 
The QUINTESSENTIAL trial met its stated primary endpoint of ORR and key secondary CRR endpoint in quadruple-class exposed patients with RRMM after ≥4 prior lines of therapy, and it also met the reported ORR and CRR endpoints in patients after ≥3 prior lines. The reported safety profile of arlocabtagene autoleucel was consistent with that of other CAR T-cell therapies and GPRC5D-targeting therapies in multiple myeloma; detailed numerical efficacy and safety results were not included in the supplied announcement. 
 
Reference: 
Bristol Myers Squibb Announces Positive Topline Results from Registrational Phase 2 QUINTESSENTIAL Trial of the Potential First-in-Class GPRC5D-Directed CAR T Cell Therapy, Arlocabtagene Autoleucel. Bristol Myers Squibb press release. September 8, 2026. 
 
 

Pomalidomide plus bortezomib and dexamethasone for newly diagnosed multiple myeloma with renal impairment: Randomized phase II study (POM-MM-003) — Med (September 2026) 
 

What is the purpose of the study? 
To evaluate whether adding pomalidomide to bortezomib and dexamethasone (PVd) improves treatment response and renal recovery compared with bortezomib and dexamethasone (Vd) in patients with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI). 
 
Summary 
The POM-MM-003 trial was an open-label, randomized phase II study conducted at eight centers in China, enrolling 82 patients with symptomatic NDMM and creatinine clearance ≥15 to <60 mL/min. Patients were randomized 2:1 to PVd (n=58) or Vd (n=24) for two 21-day induction cycles, with two additional cycles of the same treatment for patients achieving a minor response. After four induction cycles, the ≥VGPR rate was 72.4% with PVd versus 20.8% with Vd (p<0.001), while renal response was 75.9% versus 45.8% (p=0.009), respectively. Median progression-free survival (PFS) and overall survival (OS) were not reached; grade 3–4 treatment-related adverse events occurred in 41.4% and 29.2% of patients, respectively, and one treatment-related death from ileus occurred in the PVd group. 
 
Key points 
• Study design: Open-label, randomized, phase II trial at eight centers in China; 82 patients were randomized to PVd (n=58) or Vd (n=24). 
• Population: Patients with symptomatic NDMM and RI, defined as creatinine clearance ≥15 to <60 mL/min. 
• Hematologic response: After four induction cycles, ≥VGPR was achieved in 72.4% (42/58) with PVd versus 20.8% (5/24) with Vd (p<0.001). 
• Overall hematologic response: 84.5% with PVd versus 45.8% with Vd. 
• Renal response: 75.9% (44/58) with PVd versus 45.8% (11/24) with Vd (p=0.009). 
• Minimal residual disease (MRD): Among patients assessed who achieved CR or better, the MRD negativity rate was 69.2% with PVd versus 50.0% with Vd; the study notes that the small number assessed limits interpretation. 
• PFS: The 12-month PFS rate was 84.4% with PVd versus 62.5% with Vd; the risk of progression or death was lower with PVd (HR 0.36, 95% CI 0.15–0.88). 
• OS: Median OS was not reached in either group; the 24-month OS rate with PVd was 91.0%. The study states that mature long-term survival outcomes require further follow-up. 
• Safety: Grade 3–4 treatment-related adverse events occurred in 41.4% (24/58) of PVd-treated patients and 29.2% (7/24) of Vd-treated patients. Most adverse events were managed with dose modifications; one treatment-related death from ileus occurred with PVd. 
 
Strengths 
The study used the same response criteria and tumor-assessment frequency in both groups. The randomized, head-to-head design provided a direct comparison of PVd with Vd in this population. 
 
Limitations 
• Open-label design and potential investigator bias. 
• Exploratory phase II design and relatively small sample size, limiting robustness and generalizability. 
• Few patients had severe RI and none were receiving hemodialysis, so applicability may be greatest to patients with moderate RI. 
• Low transplantation rates may limit generalizability to transplant-eligible populations in regions where transplantation is routinely used. 
• MRD testing methods varied between centers, and the number of patients assessed for MRD was small. 
• The study did not require renal biopsy or systematic 24-hour urine protein electrophoresis and did not prospectively record precipitating factors for RI, limiting characterization of the underlying renal cause. 
• Participants were recruited only in China; exclusion of pregnant or lactating women and other population characteristics may limit generalizability. 
• The subgroup and survival analyses were limited by the small sample size and low number of events; subgroup analyses were exploratory and not prespecified. 
• Long-term and mature survival outcomes require additional follow-up. 
• Vd is recognized by the authors as a limitation of the contemporary comparator, and larger studies comparing PVd with more contemporary regimens, including CD38 antibody-based quadruplets, are needed. 
 
Why this study matters 
In this randomized phase II study of patients with NDMM and RI, PVd produced higher ≥VGPR and renal response rates than Vd after four induction cycles, with a 12-month PFS rate of 84.4% versus 62.5%. The safety findings were described as manageable, with no new safety signals identified, but the small, open-label phase II design, limited representation of severe RI and hemodialysis, and immature survival data limit the strength and generalizability of the findings; larger prospective studies are needed to further evaluate PVd and compare it with contemporary treatment regimens. 
 
Reference: 
Fei Xiao, Liru Wang, Fei Li, Fang Wang, Yuping Zhong, Xiaoyan Qu, Chunkang Chang, Zhenyu Li, Yang Liu, Xuelin Dou, Lei Wen, Nan Peng, Jin Lu, Jian Hou, Pomalidomide plus bortezomib and dexamethasone for newly diagnosed multiple myeloma with renal impairment: Randomized phase II study (POM-MM-003), Med, 2026, 101293, ISSN 2666-6340, https://doi.org/10.1016/j.medj.2026.101293.  

Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial — Nature Medicine (September 2026) 
 

What is the purpose of the study? 
The randomized phase 2 ImmunoPRISM trial (NCT05469893) evaluates the efficacy and safety of fixed-duration teclistamab, a B cell maturation antigen (BCMA)-targeting bispecific antibody, compared with lenalidomide–dexamethasone (Rd) in patients with high-risk smoldering multiple myeloma (HR-SMM). The primary endpoint is the rate of complete response (CR). 
 
Summary 
After a six-patient safety run-in, 59 patients were treated: 45 received teclistamab and 14 received Rd. Teclistamab treatment resulted in CR in 77.8% of patients versus 0% with Rd, while 82.2% achieved minimal residual disease (MRD) negativity at 10⁻⁵, meaning no detectable residual disease at the specified sensitivity level. At a median follow-up of 24.5 months, 2-year progression-free survival (PFS)—the proportion of patients who remained alive without disease progression—was 92% with teclistamab versus 49% with Rd; response rates, duration of response, and time to progression were also significantly improved with teclistamab. 
 
Key points 
• Study design: Multicenter, randomized phase 2 ImmunoPRISM trial. 
• Participants: 59 treated adults with HR-SMM; 45 received teclistamab and 14 received Rd. 
• Treatment duration: Teclistamab was administered for a maximum of 12 cycles (15 months) after a protocol amendment; Rd was administered for 2 years. 
• Complete response (CR): 
 - Teclistamab: 77.8% 
 - Rd: 0% 
    
• Overall response rate with teclistamab: 93.3%. 
• MRD negativity at 10⁻⁵: 82.2% of teclistamab-treated patients. 
• 2-year PFS: 
 - Teclistamab: 92% 
 - Rd: 49% 
• Response durability: At a median follow-up of 24.5 months, the study reported durable responses, and patients who achieved MRD negativity had sustained MRD negativity at the data cutoff. 
• Safety: Teclistamab was associated with grades 1–2 cytokine release syndrome (CRS), with no high-grade CRS events and no observed neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS). 
• Grade 3 infections: 20% with teclistamab versus 21% with Rd. 
• Deaths: None occurred in either treatment arm. 
• Primary nonresponse: Three patients had primary nonresponse. The study reported no identified prior BCMA exposure, BCMA mutations, or structural variants affecting the BCMA locus in these patients. 
• Biomarkers: Higher baseline soluble BCMA was associated with inferior response depth and persistent MRD positivity, but the authors stated that soluble antigen burden alone was unlikely to fully explain primary nonresponse. 
• Sex/gender analyses: The study was not designed or powered to detect sex- or gender-based differences in efficacy, toxicity, or correlative biomarkers; therefore, no formal sex- or gender-stratified analyses were performed. 
 
Strengths 
• The study was a randomized phase 2 trial directly comparing teclistamab with Rd in HR-SMM. 
• The authors reported durable responses and sustained MRD negativity at the data cutoff among patients who achieved MRD negativity. 
 
Limitations 
• The study included a small sample of 59 treated participants and a limited number of outcome events. 
• Prior SMM-directed therapy introduced some heterogeneity between treatment arms, although sensitivity analyses did not suggest a meaningful effect on outcomes. 
• Potential tumor-extrinsic factors, including baseline T-cell fitness, effector-to-target ratio, and immune microenvironmental suppression, were not comprehensively assessed. 
• The study was not designed or powered for sex- or gender-based analyses. 
• Longer follow-up is required to determine whether the deep responses and observed improvement in PFS translate into durable prevention of progression to symptomatic myeloma. 
• The current follow-up does not support conclusions regarding overall survival benefit or disease eradication. 
 
Why this study matters 
In this randomized phase 2 study, the authors concluded that teclistamab was superior to Rd, with higher rates of CR, MRD negativity, and PFS in patients with HR-SMM. At a median follow-up of 24.5 months, teclistamab was associated with frequent deep responses and a manageable safety profile, but longer follow-up is required to determine whether these findings translate into durable prevention of progression to symptomatic myeloma; no conclusions regarding overall survival benefit or disease eradication can be drawn from the current follow-up period. 
 
Reference: 
Nadeem, O., Cordas dos Santos, D.M., Magidson, S. et al. Teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma: a randomized phase 2 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04642-w 
 

National Institute for Health and Care Excellence (NICE) 
 

NICE recommends daratumumab-based quadruplet therapy for transplant-eligible multiple myeloma 

On Thursday, September 10, Johnson & Johnson announced via press release that the National Institute for Health and Care Excellence (NICE) has issued its Final Draft Guidance, recommending DARZALEX® (daratumumab) in combination with bortezomib, lenalidomide and dexamethasone (D-VRd) for adults with previously untreated multiple myeloma who are suitable for an autologous stem cell transplant (ASCT). 
 
Daratumumab is a human monoclonal antibody targeting CD38, a protein highly expressed on multiple myeloma cells. By binding to CD38, it triggers immune-mediated killing of myeloma cells and helps inhibit tumor growth. 
 
NICE’s guidance is a Final Draft Guidance rather than a final published technology appraisal recommendation. If implemented as proposed, D-VRd would add a daratumumab-based quadruplet regimen and MRD-guided maintenance strategy to the treatment pathway for ASCT-eligible adults with newly diagnosed multiple myeloma in England and Wales. 
 
The recommendation means eligible patients in England and Wales are set to gain access to D-VRd as an induction treatment before ASCT, followed by D-VRd consolidation and daratumumab plus lenalidomide maintenance. NICE also says the regimen can be used in patients who have received daratumumab, bortezomib, thalidomide and dexamethasone induction and consolidation but have not yet started maintenance treatment. 
 
Phase 3 PERSEUS Trial results 
NICE’s recommendation is based on results from the Phase 3 PERSEUS trial, a randomized, multicenter, open-label study involving patients with newly diagnosed multiple myeloma who were eligible for ASCT. 
 
At a median follow-up of 47.5 months, D-VRd followed by daratumumab plus lenalidomide maintenance reduced the risk of disease progression or death by 58% compared with bortezomib, lenalidomide and dexamethasone (VRd) followed by lenalidomide maintenance. 
 
The hazard ratio for progression-free survival (PFS) was 0.42 (95% confidence interval [CI], 0.30–0.59; P<0.001). Median PFS had not been reached in either treatment group. At 48 months, estimated PFS was 84.3% with D-VRd versus 67.7% with VRd. 
 
The trial also reported deeper responses with D-VRd. Minimal residual disease (MRD) negativity at a sensitivity of 10^-5 was achieved by 75.2% of patients receiving D-VRd compared with 47.5% receiving VRd. Complete response (CR) or better occurred in 87.9% versus 70.1%, while sustained MRD negativity for at least 12 months was reported in 64.8% versus 29.7%, respectively. 
 
Overall survival (OS) data remained immature at the reported follow-up, with deaths in 34 patients (9.6%) in the D-VRd group and 44 patients (12.4%) in the VRd group. 
 
NICE has also recommended an MRD-guided approach during maintenance treatment. Patients will undergo MRD testing using bone marrow samples. According to the Final Draft Guidance, daratumumab may be stopped after at least 24 months of maintenance if MRD has remained negative for at least 12 months, while lenalidomide maintenance can continue. 
 
NICE described the use of MRD status to guide treatment decisions as a “step change” in myeloma management. The approach could reduce treatment burden and hospital visits for eligible patients while continuing disease monitoring. 
 
Safety findings 
The safety profile of D-VRd was consistent with the known safety profiles of daratumumab and VRd in this population. 
 
Grade 3 or 4 adverse events occurred frequently in both groups. The most common were neutropenia, reported in 62.1% of patients receiving D-VRd versus 51.0% with VRd, and thrombocytopenia, reported in 29.1% versus 17.3%. 
 
Other grade 3 or 4 adverse events included diarrhoea (10.5% versus 7.8%), pneumonia (10.5% versus 6.1%), and febrile neutropenia (9.4% versus 10.1%). Grade 3 or 4 peripheral neuropathy occurred in 6.0% of patients receiving D-VRd and 4.9% receiving VRd. 
 
Serious adverse events occurred in 57.0% of patients in the D-VRd group and 49.3% in the VRd group, with pneumonia the most common serious adverse event (11.4% versus 6.1%). 
 
Despite the higher incidence of some adverse events with D-VRd, treatment discontinuation because of adverse events occurred in 8.8% of patients in the D-VRd group compared with 21.3% in the VRd group. 
 
Thalidomide-sparing treatment option 
NICE’s recommendation also provides a thalidomide-sparing quadruplet treatment option for patients eligible for ASCT. The committee noted that replacing thalidomide with lenalidomide is associated with a lower risk of peripheral neuropathy. 
 
NICE highlighted the particular importance of additional first-line options for ASCT-eligible patients, who tend to be younger and may be more likely to be working or have caring responsibilities. 
 
Reference: 
NICE issues Final Draft Guidance recommending DARZALEX® (daratumumab) plus bortezomib, lenalidomide and dexamethasone for untreated multiple myeloma when a stem cell transplant is suitable. Johnson & Johnson press release. September 10, 2026. 
 

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.