A summary of some notable key multiple myeloma research from May-June 2026  

Scope and Methodology   
This week’s blog summarizes key multiple myeloma research published in several peer-reviewed publications and medical journals from May-June 2026. Content was developed by the International Myeloma Foundation medical editorial team using various medical abstracts on new guidelines, recommendations, 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 June 24, 2026. The blog reflects medical guidance available at the time of review and is not routinely updated.  

  
Guidelines and Recommendations

European Recommendations for Transitioning the Care of Patients With Multiple Myeloma Treated With B-Cell Maturation Antigen Bispecific Antibodies From Academic Hospitals to Community-Based Centers and for Outpatient Step-Up Dosing — eJHaem (May 2026)

What is the purpose of the study? 
To develop European expert recommendations for the safe outpatient step-up dosing (SUD) of B-cell maturation antigen–targeting bispecific antibodies (BCMA-BsAbs) and for transitioning care of patients with multiple myeloma (MM) from academic to community centers, using a modified Delphi consensus process. The aim is to provide standardized guidance for patient selection, toxicity management, infection prevention, monitoring, and institutional preparedness in outpatient and community practice settings.

Summary 
A multidisciplinary panel of 53 clinicians from six European countries (including hematologists, nurses, and pharmacists) participated in a three-round modified Delphi process to establish consensus recommendations for outpatient SUD and transition of care for patients receiving BCMA-BsAbs for relapsed/refractory MM (RRMM). Consensus (defined as ≥75% agreement) was achieved for 84 statements addressing patient eligibility, center infrastructure, staff training, infection prophylaxis, remote monitoring, escalation pathways, and communication between academic and community centers.

The panel recommended that only clinically stable patients should transition to community care or undergo outpatient SUD. Recommended criteria included being afebrile for at least 24 hours, having ASTCT Grade 0 toxicity, stable organ function, low tumor burden, Eastern Cooperative Oncology Group (ECOG) performance status 0–2, reliable caregiver support, and residence within 60 minutes of an inpatient facility. Community centers were advised to have staff trained in cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) management, urgent laboratory access, on-site tocilizumab and corticosteroids, and 24/7 escalation protocols.

The consensus also emphasized proactive infection prevention. Recommendations included baseline cytomegalovirus testing, routine immunoglobulin monitoring, antiviral and Pneumocystis jirovecii pneumonia prophylaxis, and prophylactic intravenous/subcutaneous immunoglobulin (IgG) therapy for patients with IgG <400 mg/dL or recurrent infections. Specifically, 97% of panelists supported initiating and maintaining IgG prophylaxis in these patients, while 82% agreed that all patients could be considered for IgG therapy before the first BCMA-BsAb dose.

Key points

1. The study developed a European consensus framework specifically for: 
• outpatient step-up dosing (SUD) of BCMA-BsAbs 
• transition of care from academic to community centers in multiple myeloma 
• A modified Delphi methodology was used: 
 - 53 clinicians participated 
 - representation included physicians, nurses, and pharmacists 
 - clinicians came from France, Germany, Italy, Portugal, Spain, and the United Kingdom 
 - consensus threshold was ≥75% 
 - 84 statements achieved consensus

2. Recommended patient criteria for outpatient SUD or community transition included: 
• afebrile for ≥24 hours 
• ASTCT Grade 0 CRS/ICANS toxicity 
• stable organ function 
• ECOG performance status 0–2 
• low tumor burden 
• reliable, trained caregiver available 24/7 
• residence within 60 minutes of inpatient care

3. Recommended community center requirements included: 
• staff trained in CRS and ICANS recognition and management 
• urgent laboratory testing capability 
• onsite access to tocilizumab and corticosteroids 
• formalized 24/7 escalation and emergency protocols 
• coordination with intensive care and academic centers

4. Infection prevention recommendations included: 
• baseline cytomegalovirus testing 
• routine immunoglobulin monitoring 
• antiviral prophylaxis 
• Pneumocystis jirovecii pneumonia prophylaxis 
• individualized antibacterial and antifungal strategies

5. Immunoglobulin prophylaxis findings: 
• 97% agreement for prophylactic intravenous/subcutaneous IgG in patients with IgG <400 mg/dL or recurrent infections 
• 82% agreement that all patients could be considered for IgG therapy before first BCMA-BsAb dosing

6. CRS findings discussed in the paper:

• Elranatamab: 
 - 57.9% overall CRS incidence 
 - Grade 1: 43.7% 
 - Grade 2: 13.7% 
 - Grade 3: 0.5% 
 - CRS occurred mainly during SUD

• Teclistamab 
 - 72% overall CRS incidence 
 - Grade 1: 50% 
 - Grade 2: 21% 
 - Grade 3: 0.6% 
 - CRS also occurred predominantly during SUD

• Median CRS onset and duration for both agents were 2 days

The paper reported that remote monitoring strategies, including daily symptom calls, telemedicine oversight, and remote vital-sign tracking, have been used successfully for early detection of CRS and infections and may reduce the need for inpatient hospitalization during SUD.

Strengths 
• Rigorous modified Delphi methodology with predefined consensus criteria 
• Multidisciplinary and multinational European participation 
• Practical operational guidance for real-world outpatient and community implementation 
• Expanded upon prior European Myeloma Network and International Myeloma Working Group recommendations by addressing staffing, escalation pathways, infrastructure, and communication processes

Limitations 
• Recommendations were based on expert consensus rather than prospective real-world clinical studies 
• Geographic representation may not fully reflect practice variation across all European healthcare systems 
• All participating countries were high-income nations, potentially limiting applicability to low- and middle-income settings 
• Recommendations were primarily designed for subcutaneous BCMA-BsAbs and may not fully apply to intravenous BCMA-BsAbs or other bispecific antibody targets

Why this consensus matters 
This European Delphi consensus provides a structured and pragmatic framework for outpatient step-up dosing of BCMA-BsAbs and transition of care from academic to community settings for patients with multiple myeloma. The recommendations define practical standards for patient eligibility, infection prevention, toxicity management, monitoring, and institutional infrastructure to support safer implementation of outpatient and community-based care models. Although the guidance is based on expert opinion rather than prospective clinical data, it establishes a foundation for future real-world validation studies and further guideline development.

Reference: 
M. Mateos, E. Zamagni, M. Gentile, et al. “European Recommendations for Transitioning the Care of Patients With Multiple Myeloma Treated With B-Cell Maturation Antigen Bispecific Antibodies From Academic Hospitals to Community-Based Centers and for Outpatient Step-Up Dosing.” eJHaem7, no. 3 (2026): e70290. https://doi.org/10.1002/jha2.70290 (https://onlinelibrary.wiley.com/doi/10.1002/jha2.70290)

Review 

Smoldering Multiple Myeloma: Early Intervention or Structured Surveillance? A Comprehensive Review of Evidence for and Against Early Therapy — Cancers (May 2026)

What is the purpose of the review? 
To examine whether early treatment of high-risk smoldering multiple myeloma (HRSMM) improves clinical outcomes compared with active surveillance. The review evaluates evidence from clinical trials and observational studies assessing progression-free survival, overall survival, treatment-related toxicity, quality of life, and evolving risk-stratification approaches.

Summary 
Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder with variable risk of progression to active multiple myeloma. Historically, observation was the standard management approach because earlier cytotoxic therapies did not improve survival. More recent studies, including the QuiRedex, ECOG-E3A06, and phase III AQUILA trials, showed that early treatment with lenalidomide- or daratumumab-based therapy can significantly delay progression in selected patients with HRSMM, although much of the reported benefit reflects delayed biochemical or imaging-defined progression rather than confirmed prevention of symptomatic organ damage or clear long-term survival benefit.

The narrative review also highlighted that combination regimens such as KRd-based and daratumumab-containing approaches demonstrated high response rates and measurable residual disease (MRD) negativity in phase II studies, but long-term survival and quality-of-life data remain immature. The authors emphasized that risk stratification remains imperfect, treatment-related toxicity and the theoretical risk of clonal selection are ongoing concerns, and individualized decision-making remains important when considering early intervention.

Key points 
• SMM is an asymptomatic but biologically heterogeneous plasma cell disorder with variable progression risk. 
• Traditional management has been active in surveillance until progression to symptomatic myeloma. 
• Updated International Myeloma Working Group (IMWG) criteria reclassified some previously defined “HRSMM” patients as active myeloma requiring treatment. 
• The QuiRedex and ECOG-E3A06 trials showed reduced progression risk with lenalidomide-based therapy. 
• The phase III AQUILA trial demonstrated delayed progression with daratumumab in HRSMM and contributed to the November 2025 FDA approval of subcutaneous daratumumab for this indication. 
• Current evidence supports considering selective early treatment in carefully defined HRSMM populations, while acknowledging uncertainty regarding long-term survival benefit. 
• Many reported treatment benefits involve delaying biochemical or imaging-defined progression rather than confirmed prevention of irreversible organ damage. 
• MRD negativity is a promising endpoint but has not been validated as a surrogate for survival outcomes in SMM and should not currently be interpreted as evidence of cure. 
• Potential risks of early treatment include hematologic toxicity, infections, thromboembolism, hypertension, treatment burden, and the theoretical possibility of clonal selection. 
• Emerging approaches include dynamic risk models such as PANGEA and biomarkers including serum BCMA, circulating tumor DNA, and genomic profiling.

Strengths 
• Comprehensive review of historical and contemporary clinical trials in SMM. 
• Discussed evolving diagnostic criteria, risk stratification, and emerging biomarkers. 
• Included consideration of treatment toxicity, quality of life, and patient-centered outcomes. 
• Provided a balanced discussion of both benefits and limitations of early intervention.

Limitations 
• Narrative review design rather than a systematic review or meta-analysis. 
• Many cited studies had immature overall survival and long-term follow-up data. 
• Variability in risk-stratification models and evolving diagnostic criteria complicates comparison across studies. 
• Some benefits may reflect lead-time bias due to reclassification of patients under updated IMWG criteria.

Why this review matters 
Current evidence suggests that early lenalidomide- or daratumumab-based therapy can delay progression in selected patients with HRSMM, although it remains uncertain whether this translates into consistent long-term survival benefit or prevention of symptomatic organ damage. Active surveillance continues to be appropriate for many patients, and treatment decisions should be individualized using validated risk assessment, serial disease monitoring, and patient preferences. Future research should focus on survival outcomes, quality of life, molecular risk prediction, MRD-guided treatment strategies, and the long-term effects of early intervention on disease biology and treatment resistance.

Reference: 
Arora, K., Soueid, L., Williams, L., Grover, J., Basali, D., Khouri, J., Kaushal, Y., Mazzoni, S., Dahiya, R., Faiman, B., Valent, J., Anwer, F., & Raza, S. (2026). Smoldering Multiple Myeloma: Early Intervention or Structured Surveillance? A Comprehensive Review of Evidence for and Against Early Therapy. Cancers, 18(10), 1505. https://doi.org/10.3390/cancers18101505 (https://www.mdpi.com/2072-6694/18/10/1505)

Treatment Intensity in the Frontline Setting for Transplant-Ineligible Patients With Multiple Myeloma — JADPRO (May 2026)

What is the purpose of the review? 
To evaluate data from the phase III IMROZ and CEPHEUS trials to assess the efficacy and safety of CD38-based quadruplet therapy compared with triplet therapy in patients with newly diagnosed, transplant-ineligible multiple myeloma (TI-NDMM), including frailty-defined subgroups. The analysis focused on progression-free survival (PFS), minimal residual disease (MRD) negativity, tolerability, and the challenges of treating frail patients using different frailty assessment models.

Summary 
The IMROZ and CEPHEUS phase III randomized trials compared CD38-based quadruplet regimens with standard VRd (bortezomib, lenalidomide, dexamethasone) triplet therapy in newly diagnosed multiple myeloma. IMROZ evaluated isatuximab-VRd (Isa-VRd) versus VRd in a strictly transplant-ineligible population, while CEPHEUS evaluated daratumumab-VRd (D-VRd) versus VRd in a broader frontline population that included transplant-ineligible patients and patients who deferred autologous stem cell transplantation (ASCT). Subgroup analyses from both trials reported longer PFS and higher MRD negativity rates with quadruplet therapy compared with triplet therapy, including in frail and intermediate-fit patient subgroups.

Both trials also reported substantial treatment-related toxicity, particularly among frail patients. Frail patients generally experienced lower PFS, lower MRD negativity rates, and higher toxicity rates than non-frail patients. Rates of grade ≥3 adverse events exceeded 90% across treatment arms in both studies, with hematologic toxicities such as neutropenia occurring more frequently with quadruplet therapy. The review also emphasized that differing frailty scoring systems and restrictive eligibility criteria limited cross-trial comparisons and reduced the applicability of findings to older and medically vulnerable patients commonly encountered in routine practice.

Key points 
• IMROZ evaluated Isa-VRd versus VRd in TI-NDMM patients. 
• CEPHEUS evaluated D-VRd versus VRd in a broader frontline population that included transplant-ineligible patients and patients who deferred ASCT. 
• Subgroup analyses from both trials reported longer PFS and higher MRD negativity rates with quadruplet therapy compared with triplet therapy. 
• Improved PFS and MRD negativity outcomes with quadruplet therapy were also reported in frail and intermediate-fit patient subgroups. 
• Frail patients generally experienced lower PFS, lower MRD negativity rates, and higher toxicity rates than non-frail patients. 
• Rates of grade ≥3 adverse events exceeded 90% across treatment arms in both studies. 
• Hematologic toxicities, particularly neutropenia, occurred more frequently with quadruplet therapy. 
• Both studies excluded many patients commonly seen in practice, including patients older than 80 years and those with substantial comorbidities or poor performance status. 
• Frailty assessment methods differed between studies, limiting direct cross-trial comparisons.

Strengths 
• Included data from two phase III randomized clinical trials. 
• Evaluated treatment outcomes within frailty-defined subgroups, an understudied population in multiple myeloma research. 
• Examined both efficacy and toxicity outcomes.

Limitations 
• The review summarized subgroup analyses rather than reporting prespecified primary analyses focused on frailty. 
• Differences in trial populations and frailty assessment tools limited direct comparison between IMROZ and CEPHEUS. 
• Trial eligibility criteria excluded many older and medically vulnerable patients, limiting applicability to real-world populations. 
• Additional real-world data are needed to better characterize tolerability and patient selection.

Why this review matters 
Data from the IMROZ and CEPHEUS trials suggest that CD38-based quadruplet therapy was associated with improved PFS and higher MRD negativity rates compared with triplet therapy in NDMM, including among clinically selected frail patient subgroups enrolled in the trials. However, treatment-related toxicity remained substantial, particularly in frail populations, and the enrolled trial populations may not fully reflect patients commonly encountered in clinical practice. Additional real-world and prospective studies are needed to clarify patient selection, tolerability, and the role of treatment modifications in vulnerable patient groups.

Reference: 
Davis M. Treatment Intensity in the Frontline Setting for Transplant-Ineligible Patients With Multiple Myeloma. J Adv Pract Oncol. 2026 May 6:1-8. doi: 10.6004/jadpro.2026.17.7.14. (https://jadpro.com/online-first/2026/treatment-intensity-in-the-frontline-setting-for-transplant-ineligible-patients-with-multiple-myeloma/)

 
Melflufen in Multiple Myeloma: Clinical Limitations, Biological Rationale, and Future Perspectives — Cancers (May 2026)

What is the purpose of the review? 
This narrative review summarizes the biological rationale, preclinical findings, clinical trial results, and regulatory history of melflufen (melphalan flufenamide) in relapsed or refractory multiple myeloma (RRMM). It also examines its outcomes across key studies, including the phase III OCEAN trial, and describes its current, more limited role in treatment.

Summary  
Melflufen is a peptide–drug conjugate designed to deliver the chemotherapy agent melphalan into myeloma cells using aminopeptidase activity, leading to increased intracellular drug exposure and cancer cell death in laboratory studies, although patient-level predictive biomarkers have not yet been established. Early clinical trials (O-12-M1 and HORIZON) showed modest response rates in heavily pretreated RRMM, including in triple-class refractory disease, but were also associated with frequent blood-related side effects such as low platelets, low white blood cells, and anemia, which sometimes required treatment adjustments and supportive care. In the phase III OCEAN trial, melflufen plus dexamethasone improved progression-free survival compared with pomalidomide plus dexamethasone (6.8 vs 4.9 months) but was associated with lower overall survival (19.8 vs 25.0 months); the reasons for this survival difference are not fully understood and may relate to differences in patient subgroups (such as timing of relapse after transplant), subsequent treatments received after disease progression, and other study-related factors, leading to withdrawal of approval in the United States and more restricted use in Europe.

Key points

• Mechanism: Melflufen is designed to enter cells and release melphalan inside tumor cells through aminopeptidase activity; this targeted activation is supported by laboratory studies but not yet validated using clinical biomarkers.

• Preclinical findings: Shows activity against multiple myeloma cells, including drug-resistant models, and may also affect the bone marrow environment, including stromal cells and pathways involved in blood vessel formation and bone remodeling.

• Early clinical trials (O-12-M1, HORIZON): Demonstrated response rates of roughly 29–31% in heavily pretreated RRMM, with median progression-free survival around 4–6 months; blood-related toxicities were common and sometimes clinically significant.

• Phase III OCEAN trial: Improved progression-free survival but showed lower overall survival compared with pomalidomide; the survival difference remains incompletely explained and may be influenced by patient characteristics, especially prior transplant status and timing of relapse, as well as differences in subsequent therapies and study context.

• Regulatory outcomes: Initially received accelerated FDA approval (2021), later withdrawn after OCEAN results; in Europe, approval was more limited to selected patients without early relapse after transplant.

• Combination studies: Early studies combining melflufen with agents like daratumumab or bortezomib showed encouraging response rates, but these findings come from small, non-randomized studies and are not confirmatory.

• Real-world evidence: Suggests the drug may have activity in heavily pretreated patients, but available data are limited by small sample sizes, differences between studies, and retrospective design.

• Safety profile: Most side effects involve the blood system (low platelets, white blood cells, and red blood cells); these can be clinically important and may require dose delays, reductions, transfusions, or growth factor support.

• Limitations: No validated biomarkers to identify which patients benefit most, and uncertainty remains about the overall survival findings and optimal place of the drug in modern multiple myeloma treatment.

Why this review matters 
Melflufen is a chemotherapy-based approach that uses a targeted delivery system to increase melphalan activity inside myeloma cells, with early studies showing modest clinical benefits in heavily pretreated disease. However, a large phase III trial showed improved disease control time but reduced overall survival compared with standard therapy, and the reason for this difference has not been fully clarified. As a result, its use is now more limited, and future development would depend on better patient selection strategies and clearer understanding of which patients, if any, may benefit.

Reference: 
Garibotto, M., Soncini, D., Lemoli, R. M., Cagnetta, A., & Cea, M. (2026). Melflufen in Multiple Myeloma: Clinical Limitations, Biological Rationale, and Future Perspectives. Cancers, 18(10), 1551. https://doi.org/10.3390/cancers18101551 (https://www.mdpi.com/2072-6694/18/10/1551)

Talquetamab: Mechanism of Action, Clinical, and Translational Science — Clinical and Translational Science (May 2026)

What is the purpose of the review? 
To review the clinical pharmacology, mechanism of action, dosing rationale, efficacy, safety, and immunogenicity of talquetamab in patients with relapsed/refractory multiple myeloma (RRMM). The objective is to evaluate how talquetamab targets GPRC5D-expressing malignant plasma cells, support dose selection, and characterize its benefit–risk profile in heavily pretreated patients.

Summary 
Talquetamab is a first-in-class bispecific antibody that targets GPRC5D on malignant plasma cells and CD3 on T cells, promoting T-cell activation and lysis of GPRC5D-expressing cells. Clinical development was primarily based on the Phase I/II MonumenTAL-1 Study study, which evaluated intravenous and subcutaneous dosing regimens in adults with heavily pretreated RRMM. Recommended subcutaneous regimens of 0.4 mg/kg weekly and 0.8 mg/kg every 2 weeks produced overall response rates (ORR) of 74% (95% CI 66–81) and 69% (95% CI 62–77), respectively, while patients previously treated with T-cell redirection therapies had an ORR of 67% (95% CI 55–77).

Common adverse events included predominantly grade 1–2 cytokine release syndrome (CRS), infections, dysgeusia (taste alterations), and hematologic toxicities such as neutropenia, anemia, and lymphopenia. Most CRS events occurred during step-up dosing or the first full treatment dose and were commonly managed with supportive measures including tocilizumab and corticosteroids. Anti-drug antibodies developed in 35.8% of participants, including neutralizing antibodies in 18.2%, but no clinically meaningful effects on pharmacokinetics, efficacy, or safety were observed. Pharmacokinetic and exposure–response analyses supported both approved subcutaneous dosing schedules.

Key points 
• Talquetamab is a bispecific antibody targeting GPRC5D and CD3 to redirect T cells against GPRC5D-expressing malignant plasma cells. 
• GPRC5D expression is primarily restricted to malignant plasma cells and certain keratinized tissues, supporting its potential as a therapeutic target with limited off-tumor effects. 
• Recommended dosing regimens: 
 - 0.4 mg/kg subcutaneous weekly (QW) 
 - 0.8 mg/kg subcutaneous every 2 weeks (Q2W)

• In the MonumenTAL-1 Study: 
 - ORR was 74% (95% CI 66–81) with 0.4 mg/kg QW 
 - ORR was 69% (95% CI 62–77) with 0.8 mg/kg Q2W 
 - ORR was 67% (95% CI 55–77) in patients previously treated with T-cell redirection therapies

• Common adverse events: 
 - Cytokine release syndrome (73–79%), predominantly grade 1–2 
 - Dysgeusia/taste alterations (71–76%) 
 - Infections (59–76%)

• Most common grade 3–4 toxicities: 
 - Neutropenia 
 - Anemia 
 - Lymphopenia

• CRS events were mainly observed during step-up dosing and initial treatment doses and were commonly managed with tocilizumab and corticosteroids. 
• Anti-drug antibodies occurred in 35.8% of patients, including neutralizing antibodies in 18.2%, without clinically meaningful impact on efficacy, pharmacokinetics, or safety. 
• Pharmacokinetic analyses supported both weekly and every-2-week subcutaneous dosing schedules. 
• No fatal adverse events were considered related to talquetamab treatment. 
• Ongoing trials evaluate talquetamab in earlier treatment settings and combination regimens.

Strengths 
• Large multicenter Phase I/II clinical dataset in heavily pretreated RRMM patients. 
• Comprehensive assessment of pharmacokinetics, pharmacodynamics, immunogenicity, efficacy, and safety. 
• Included evaluation of both intravenous and subcutaneous administration approaches. 
• Exposure–response analyses supported evidence-based dose selection.

Limitations 
• The study was primarily open-label and non-randomized. 
• Long-term efficacy and safety data remain under ongoing evaluation. 
• CRS, infections, and hematologic toxicities remained common despite mitigation strategies. 
• Accelerated approval in the United States and conditional authorization in the European Union require confirmatory studies.

Why this review matters 
Talquetamab demonstrated clinically meaningful antitumor activity in heavily pretreated relapsed/refractory multiple myeloma, with overall response rates of 67–74% across evaluated patient groups and supported weekly or every-2-week subcutaneous dosing schedules. The safety profile was characterized by frequent but predominantly low-grade CRS, infections, dysgeusia, and hematologic toxicities, while immunogenicity did not show clinically meaningful effects on treatment outcomes. Ongoing clinical trials are further evaluating talquetamab in combination regimens and earlier lines of therapy to better define its long-term efficacy and safety profile.

Reference: 
Y. Wang, J. Gong, N. Au, et al., “Talquetamab: Mechanism of Action, Clinical, and Translational Science,” Clinical and Translational Science19, no. 5 (2026): e70574, https://doi.org/10.1111/cts.70574 (https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70574).

Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen–Directed CAR T-Cell Therapy — BioDrugs (May 2026)

What is the purpose of the review? 
To summarize the safety profile of B-cell maturation antigen (BCMA)-directed CAR T-cell therapies in patients with relapsed/refractory multiple myeloma. It describes common and rare toxicities, their timing and variability, and reports evidence on non-relapse mortality and potential management considerations.

Summary 
BCMA-directed CAR T-cell therapies, including idecabtagene vicleucel and ciltacabtagene autoleucel, are associated with cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS), hematotoxicity, and infections, as well as less frequent events such as parkinsonian-like movement disorders, immune-mediated enterocolitis, hemophagocytic lymphohistiocytosis, and secondary malignancies. Reported non-relapse mortality is approximately 8% in a meta-analysis and 9–10% in real-world cilta-cel data, with infections and cardiopulmonary or neurotoxicity-related events described as contributing causes. Differences in toxicity timing are reported, with earlier onset CRS for ide-cel and delayed onset CRS and delayed neurotoxicity, including movement disorders, more often described with cilta-cel; investigational agents such as anitocabtagene autoleucel are being evaluated in early-phase studies, where no delayed neurotoxicity has been reported so far.

Key points 
• Toxicities reported with BCMA CAR T-cell therapy 
 - Cytokine release syndrome (CRS) 
 - ICANS (immune effector cell-associated neurotoxicity syndrome) 
 - Hematotoxicity 
 - Infections

• Less frequent adverse events reported 
 - Parkinsonian-like movement disorders 
 - Immune-mediated enterocolitis 
 - Hemophagocytic lymphohistiocytosis 
 - Secondary malignancies

• Non-relapse mortality (NRM) 
 - ~8% in meta-analysis 
 - ~9–10% in real-world cilta-cel cohort 
 - Reported causes include infections and cardiopulmonary or neurotoxicity-related events

• Reported differences between products 
 - ide-cel: CRS onset typically 1–2 days after infusion 
 - cilta-cel: CRS onset median ~7 days after infusion 
 - cilta-cel: delayed neurotoxicity including movement disorders reported more frequently

• Bridging therapy (reported observations) 
 - Response to bridging therapy is reported to be associated with lower adverse events and lower NRM in some studies 
 - Deeper responses before infusion are reported to be associated with improved outcomes

• Investigational therapy 
 - anitocabtagene autoleucel is under evaluation in early-phase studies (e.g., iMMagine-1) 
 - No delayed neurotoxicity reported so far in these studies 
 - Longer follow-up is required to further characterize safety

Strengths 
• Summarizes reported toxicities across clinical trial and real-world data 
• Includes both common and less frequent adverse events 
• Reports observed differences in toxicity timing between products

Limitations 
• Based on heterogeneous studies and data sources 
• Limited long-term safety data for newer or investigational constructs 
• Mechanistic explanations are not fully established in the source

Why this review matters 
BCMA-directed CAR T-cell therapies are associated with a range of toxicities, including common inflammatory and neurologic events and less frequent serious complications. Reported differences in timing and type of toxicities exist between ide-cel and cilta-cel, while overall non-relapse mortality is approximately 8–10% in available studies. Investigational therapies such as anitocabtagene autoleucel are being evaluated in early-phase trials, but longer follow-up is needed to better define their safety profile.

Reference: 
Kuipers, M.T., Migchelbrink, J., Kramer, A.M. et al. Balancing Efficacy and Safety in Multiple Myeloma Patients Receiving B cell Maturation Antigen–Directed CAR T-Cell Therapy. BioDrugs (2026). https://doi.org/10.1007/s40259-026-00784-y (https://link.springer.com/article/10.1007/s40259-026-00784-y)

 
Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma — The FEBS Journal (May 2026)

What is the purpose of the review? 
To examine the biological mechanisms underlying resistance to immunomodulatory drugs (IMiDs) such as lenalidomide and pomalidomide in multiple myeloma (MM). It also evaluates investigational and emerging therapeutic strategies, including cereblon E3 ligase modulators (CELMoDs), immunotherapies, and epigenetic approaches, that may help address treatment resistance in relapsed and refractory disease.

Summary 
IMiDs remain central components of treatment for newly diagnosed (NDMM) and relapsed/refractory multiple myeloma (RRMM), often combined with proteasome inhibitors, dexamethasone, and anti-CD38 monoclonal antibodies. However, most patients eventually develop resistance. This review summarizes evidence showing that resistance arises through multiple mechanisms, including alterations in the cereblon (CRBN) pathway, genetic and epigenetic changes, activation of signaling pathways such as JAK/STAT and MEK/ERK, and dysfunction of the bone marrow immune microenvironment.

The authors discuss how newer CELMoDs, including iberdomide and mezigdomide, have shown promising activity in early-phase studies involving heavily pretreated and IMiD-refractory patients, potentially related to stronger CRBN binding and enhanced degradation of target proteins. The review also examines approved and investigational approaches involving CAR T-cell therapies, bispecific T-cell engagers, antibody–drug conjugates, BCL-2 inhibitors such as venetoclax in t(11;14) disease, and epigenetic therapies targeting EZH2, NSD2, and CBP/EP300 pathways. Several ongoing and early-phase clinical trials are highlighted as potential strategies to restore IMiD sensitivity or improve outcomes in resistant disease, although many approaches remain under clinical evaluation.

Key points 
• IMiDs such as lenalidomide and pomalidomide are foundational therapies for MM, but resistance commonly develops over time. 
• Resistance mechanisms are categorized into: 
 - CRBN-dependent mechanisms: reduced CRBN expression, CRBN mutations, splice variants, and alterations in the CRBN signaling complex. 
 - CRBN-independent mechanisms: activation of JAK/STAT, MEK/ERK, Wnt/β-catenin, CDK6, and MYC-related pathways.

• Immune dysfunction contributes substantially to resistance: 
 - Reduced NK-cell activity 
 - T-cell exhaustion markers (PD-1, TIGIT, LAG-3) 
 - Expansion of immunosuppressive cell populations such as regulatory T cells and myeloid-derived suppressor cells.

• Epigenetic alterations, including DNA methylation and histone modification changes, may contribute to resistant disease and are being investigated as potentially targetable mechanisms. 
• CELMoDs (iberdomide and mezigdomide) have shown promising activity in early-phase studies involving heavily pretreated RRMM and IMiD-refractory multiple myeloma. 
• Therapeutic approaches discussed include: 
 - CAR T-cell therapies 
 - Bispecific T-cell engagers targeting BCMA, GPRC5D, and FcRH5 
 - Antibody–drug conjugates 
 - Venetoclax for t(11;14) disease 
 - Epigenetic therapies combined with IMiDs or immunotherapy.

• Clinical studies discussed include: 
 - OPTIMISMM (NCT01734928) 
 - MANHATTAN (NCT03290950) 
 - CC-220-MM-001 
 - PERSEUS 
 - MIDAS 
 - IMROZ 
 - MonumenTAL-6 (NCT06208150)

Strengths 
• Comprehensive review integrating molecular, immunologic, genetic, and epigenetic mechanisms of IMiD resistance. 
• Includes both preclinical and clinical evidence across newly diagnosed and relapsed/refractory multiple myeloma. 
• Discusses ongoing therapeutic development and clinical trial strategies relevant to current treatment practice.

Limitations 
• Much of the evidence for resistance mechanisms and resensitization strategies remains preclinical or derived from early-phase clinical studies. 
• Some proposed therapeutic combinations and biomarkers have not yet been validated in randomized clinical trials. 
• As a narrative review, conclusions depend on available published literature and may evolve as new evidence emerges.

Why this review matters 
This review highlights that resistance to IMiD-based therapy in multiple myeloma is multifactorial, involving CRBN-related alterations, immune dysregulation, signaling pathway activation, and epigenetic changes. Several investigational strategies, including CELMoDs, immunotherapy combinations, and epigenetic-targeted approaches, are being studied to address resistance, though many require further clinical validation before their role in routine care can be established.

Reference: 
Fuentes-Lacouture MC, Nandana D, Ramasamy K, Thakurta A. Understanding and addressing resistance to IMiDs immunomodulatory compounds in multiple myeloma. FEBS J. 2026 May 21. doi: 10.1111/febs.70599. (https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.70599)  

Smoldering Multiple Myeloma: From Clinical to Immunogenomic Risk Stratification and Therapeutic Implications of Early Intervention — ASCO Educational Book (May 2026)

What is the purpose of the review? 
To examine current approaches to risk stratification and early intervention in smoldering multiple myeloma (SMM), focusing on how clinical, genomic, and immune profiling may improve prediction of progression to symptomatic multiple myeloma (MM). It also evaluates evidence from clinical trials assessing whether early treatment in selected patients with high-risk SMM can delay progression and potentially affect survival outcomes.

Summary 
Smoldering multiple myeloma is an asymptomatic precursor condition that exists along a biologic continuum between monoclonal gammopathy of undetermined significance (MGUS) and active MM. Traditional clinical risk models, particularly the International Myeloma Working Group (IMWG) 20/2/20 model, estimate progression risk using tumor burden markers such as serum M-protein, bone marrow plasma cells, and free light chain ratio, with high-risk disease associated with an approximately 40%–50% risk of progression within 2 years. Emerging genomic studies suggest that SMM may include biologically distinct subgroups, including patients with genomic features similar to active MM and others with lower-risk MGUS-like biology.

The review summarizes evidence from randomized phase III trials including QuiRedex, E3A06, and AQUILA, which used differing eligibility criteria and definitions of high-risk SMM but consistently demonstrated delayed progression to symptomatic MM with early intervention compared with observation. QuiRedex demonstrated an overall survival benefit with lenalidomide plus dexamethasone, while AQUILA demonstrated improved progression-free survival and a trend toward overall survival benefit with daratumumab. The article also discusses evolving genomic and immune biomarkers, dynamic risk models such as PANGEA, and investigational treatment approaches including daratumumab-based combinations, bispecific antibodies, and CAR T-cell therapies.

Key points 
• SMM is a heterogeneous precursor condition with variable risk of progression to active MM. 
• The IMWG 20/2/20 model identifies high-risk SMM using: 
 - Serum M-protein >2 g/dL 
 - Bone marrow plasma cells >20% 
 - Involved/uninvolved free light chain ratio >20

• Patients with ≥2 risk factors have an estimated 2-year progression risk of approximately 40%–50%. 
• Adverse cytogenetic abnormalities associated with higher progression risk include: 
 - del13q 
 - t(4;14) 
 - t(14;16) 
 - +1q gain

• Genomic alterations associated with increased progression risk include: 
 - KRAS and NRAS mutations 
 - TP53 and ATM abnormalities 
 - MYC alterations 
 - APOBEC mutational signatures

• Emerging genomic studies suggest that some patients with SMM have genomic profiles similar to active MM, while others demonstrate lower-risk MGUS-like biology. 
• Immune microenvironment alterations, including changes in T-cell populations and immune surveillance, may contribute to disease progression. 
• Three randomized phase III trials (QuiRedex, E3A06, and AQUILA) reported delayed progression with early intervention compared with observation, although study populations and progression criteria differed across trials. 
• QuiRedex demonstrated an overall survival benefit, while AQUILA showed a trend toward improved overall survival. 
• Daratumumab monotherapy is currently the only approved therapy for high-risk SMM in some regions. 
• Dynamic risk models such as PANGEA may improve individualized risk prediction by incorporating longitudinal biomarker changes.

Strengths 
• Integrates clinical, genomic, and immune-based evidence related to SMM progression and treatment. 
• Includes long-term follow-up data from major randomized phase III studies. 
• Discusses limitations of static clinical risk models and potential refinement through biologic profiling.

Limitations 
• Many genomic and immune profiling approaches are not yet routinely available in clinical practice. 
• Clinical trials differed in diagnostic criteria, eligibility definitions, and progression endpoints, limiting direct comparison across studies. 
• Several emerging therapies are supported primarily by early-phase or small-cohort studies with limited long-term follow-up. 
• Optimal treatment selection, treatment duration, and integration of genomic tools into routine care remain uncertain.

Why this review matters 
This review highlights the biologic heterogeneity of high-risk SMM and the potential role of integrating clinical, genomic, and immune profiling to improve risk stratification. Evidence from randomized trials indicates that early intervention can delay progression to symptomatic MM in selected patients with high-risk disease, although definitive overall survival evidence remains limited. Current evidence supports a risk-adapted and individualized approach using validated clinical models such as IMWG 20/2/20, with future refinement expected through incorporation of genomic and dynamic risk assessment strategies.

Reference: 
Nizar J. Bahlis et al. Smoldering Multiple Myeloma: From Clinical to Immunogenomic Risk Stratification and Therapeutic Implications of Early Intervention. Am Soc Clin Oncol Educ Book 46, e517488(2026). DOI:10.1200/EDBK-26-517488 (https://ascopubs.org/doi/10.1200/EDBK-26-517488)

 
Incorporating the Next Generation of Immunotherapies Into the Treatment of Multiple Myeloma — Journal of the National Comprehensive Cancer Network (May 2026)

What is the purpose of the review? 
This review summarizes the current landscape of immunotherapy in multiple myeloma (MM), including CAR T-cell therapies, bispecific antibodies (BsAbs), and antibody–drug conjugates (ADCs). It also discusses their clinical efficacy, safety profiles, and the rationale for moving these therapies into earlier lines of treatment and future investigational strategies.

Summary  
Standard frontline MM therapy using quadruplet regimens (anti-CD38 monoclonal antibody, immunomodulatory drug, proteasome inhibitor, and corticosteroid) followed by autologous stem cell transplantation (ASCT) can achieve deep and durable responses, with the PERSEUS trial reporting 4-year progression-free survival (PFS) of 84%. In relapsed/refractory MM, BCMA-directed CAR T-cell therapies such as idecabtagene vicleucel (ORR 84%, median PFS 11.8 months) and ciltacabtagene autoleucel (ORR up to 98%, median PFS 34.9 months) demonstrate high response rates but are associated with toxicities including cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), cytopenias, and infections. Bispecific antibodies (e.g., teclistamab, elranatamab, linvoseltamab) show ORRs of approximately 60%–70% with durable responses but carry risks of CRS and significant infectious complications, while belantamab mafodotin (BCMA-directed ADC) shows ORRs of ~30%–34% with notable ocular toxicity. 
 

Key points  
• Therapeutic advances 
 - CAR T-cell therapies (ide-cel, cilta-cel) produce deep responses, including high MRD negativity rates. 
 - Bispecific antibodies targeting BCMA and GPRC5D provide effective off-the-shelf immune engagement. 
 - ADCs like belantamab mafodotin offer non–T-cell–redirecting immune-based treatment options.

• Efficacy signals 
 - Cilta-cel: ORR up to 98%, median PFS 34.9 months. 
 - Ide-cel: ORR 84%, median PFS 11.8 months. 
 - BsAbs: ORR ~60%–70%, median duration of response 18–29 months. 
 - Belantamab mafodotin: ORR ~30%–34%.

• Safety considerations 
 - CAR T-cell therapy: CRS, ICANS, prolonged cytopenias, infections, rare delayed neurotoxicity. 
 - BsAbs: CRS, ICANS (less frequent), high infection risk requiring prophylaxis. 
 - Belantamab mafodotin: ocular toxicity (keratopathy, visual impairment).

Strengths 
• High response rates with multiple novel immune mechanisms. 
• Demonstrated durable remissions in heavily pretreated patients. 
• Expansion into earlier lines of therapy supported by emerging trials.

Limitations 
• Lack of established sequencing strategies for immunotherapies. 
• Risk of antigen loss (e.g., BCMA mutations/deletions) contributing to relapse. 
• Significant infectious and immune-related toxicities, especially with combination or early-line use. 
• Limited long-term comparative data in randomized settings for many newer approaches.

Why this review matters 
Immunotherapy, particularly CAR T-cell therapies and bispecific antibodies targeting BCMA and other antigens, has substantially improved outcomes in RRMM by inducing deep and sometimes durable responses. However, these benefits are accompanied by clinically meaningful toxicities, including infections and immune-related adverse events, and optimal sequencing and long-term management strategies remain undefined. Ongoing clinical trials are evaluating earlier use and combination approaches, but randomized data are still needed to determine their impact on long-term survival and treatment-related risk balance.

Reference: 
Miller, K. C., Firestone, R. S., & Hultcrantz, M. (2026). Incorporating the Next Generation of Immunotherapies Into the Treatment of Multiple Myeloma. Journal of the National Comprehensive Cancer Network (published online ahead of print 2026). https://doi.org/10.6004/jnccn.2026.7004 (https://jnccn.org/view/journals/jnccn/aop/article-10.6004-jnccn.2026.7004/article-10.6004-jnccn.2026.7004.xml)

High-Risk Multiple Myeloma: Redefining Risk and Rethinking Therapy — ASCO Educational Book (May 2026)

What is the purpose of the review? 
To provide a modern framework for defining, identifying, and understanding the biology of high-risk multiple myeloma (HRMM), a subgroup of multiple myeloma associated with early treatment resistance and poor survival. It also examines current and emerging treatment strategies, including targeted therapies and immunotherapies, to assess whether they may improve outcomes in patients with HRMM.

Summary 
HRMM accounts for approximately 15%–25% of newly diagnosed myeloma (NDMM) cases and is characterized by adverse genetic abnormalities, early treatment resistance, an increased risk of relapse, and shorter survival compared with standard-risk disease. The review describes the molecular and biological features of HRMM, including TP53 abnormalities, chromosome 1 alterations, adverse immunoglobulin heavy-chain translocations such as t(4;14) and t(14;16), immune evasion, enhanced proliferation, and genomic complexity, while emphasizing the biological heterogeneity within this patient population.

The authors discuss the recently developed Consensus Genomic System (CGS) for identifying HRMM, which incorporates combinations of high-risk cytogenetic and molecular abnormalities ("double-hit" disease). They also review evidence supporting intensive upfront treatment, autologous stem cell transplantation, risk-adapted maintenance therapy, minimal residual disease (MRD) monitoring, and emerging immunotherapies such as bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell (CAR-T) therapies. Although these newer therapies have improved response rates and progression-free survival, adverse disease biology—including extramedullary disease, advanced-stage disease, and high tumor burden—continues to contribute to early relapse and poorer long-term outcomes in many patients with HRMM.

Key points

Background 
• HRMM represents approximately 15%–25% of newly diagnosed multiple myeloma cases. 
• Outcomes for HRMM have improved less than those for standard-risk or intermediate-risk multiple myeloma despite major therapeutic advances. 
• The prevalence of HRMM increases with successive relapses.

Biological Features of HRMM 
• High-risk disease is commonly associated with abnormalities involving: 
 - del(17p) and/or TP53 abnormalities 
 - Adverse immunoglobulin heavy-chain translocations: t(4;14), t(14;16), and t(14;20) 
 - Chromosome 1q gain/amplification 
 - Chromosome 1p deletion

• In the CGS framework, combinations of these abnormalities are particularly associated with adverse outcomes. 
• HRMM is associated with: 
 - Extramedullary disease (EMD) 
 - Plasma cell leukemia (PCL) 
 - Immune evasion 
 - Increased genomic instability 
 - Enhanced proliferation 
 - Resistance to therapy

• HRMM is biologically heterogeneous and comprises multiple molecular subgroups that may respond differently to treatment.

Risk classification 
• The Consensus Genomic System (CGS) uses combinations of adverse molecular features to identify HRMM. 
• Approximately 23% of newly diagnosed patients meet CGS-defined high-risk criteria, increasing to about 30% when elevated β2-microglobulin is included. 
• In validation studies: 
 - Patients with adverse translocations plus at least one additional high-risk abnormality had median progression-free survival (PFS) of less than 30 months. 
 - Patients with more than one high-risk abnormality had a median PFS of 18 months. 
 - Patients with more than two high-risk abnormalities had a median PFS of 7 months. 
• Functional high-risk myeloma may occur in patients with clinically aggressive disease despite the absence of detectable high-risk molecular features.

Current treatment approaches 
• Four-drug induction regimens followed by high-dose melphalan and autologous stem cell transplantation remain standard treatment for eligible patients. 
• In the DETERMINATION trial: High-risk patients receiving transplantation had median PFS of 55.5 months versus 17.1 months in the non-transplant arm. 
• Maintenance therapy is considered a key component of treatment in HRMM and may require risk-adapted approaches rather than a uniform strategy for all patients.

Role of MRD 
• MRD negativity is associated with longer progression-free survival. 
• Sustained MRD negativity at a sensitivity of at least 10⁻⁶ is increasingly viewed as an important long-term treatment objective. 
• Evidence is insufficient to routinely use MRD results alone for treatment de-escalation in HRMM.

Emerging immunotherapies 
• The review describes BCMA-directed therapies including: 
 - teclistamab 
 - elranatamab 
 - linvoseltamab 
 - idecabtagene vicleucel (ide-cel) 
 - ciltacabtagene autoleucel (cilta-cel)

• Other targeted immunotherapies include: 
 - talquetamab (GPRC5D-directed) 
 - belantamab-based combinations

• In RRMM studies, these therapies have produced high response rates and deep responses, although outcomes remain less favorable in patients with: 
 - Extramedullary disease 
 - Advanced-stage disease (including R-ISS stage III) 
 - High tumor burden

• Dual-targeting and combination immunotherapy strategies may help address treatment resistance and antigen escape.

Future directions 
• Earlier integration of immunotherapies may improve outcomes and is being actively investigated. 
• Achieving durable MRD negativity and preventing clonal escape are major therapeutic goals. 
• Precision medicine approaches based on underlying disease biology are likely needed to further improve outcomes in HRMM.

Strengths 
• Provides a comprehensive overview of HRMM biology, classification, and treatment. 
• Integrates molecular, genomic, and clinical evidence into a unified framework. 
• Reviews contemporary clinical trial data and emerging immunotherapy strategies. 
• Highlights the importance of standardized definitions for future research and clinical trials.

Limitations 
• This is a narrative review rather than a prospective clinical study. 
• Many emerging therapies and treatment strategies discussed remain under investigation. 
• Some proposed biological mechanisms and molecular classifications require further validation in larger clinical datasets. 
• Long-term outcomes and optimal sequencing of newer immunotherapies remain uncertain.

Why this review matters 
HRMM is a biologically heterogeneous form of myeloma characterized by adverse molecular features, early treatment resistance, increased risk of relapse, and poorer survival outcomes. The Consensus Genomic System provides a more standardized approach to identifying patients at highest risk, while advances in transplantation, maintenance therapy, and immunotherapies have improved outcomes. MRD monitoring has become an important tool for disease assessment and treatment evaluation; however, adverse disease biology (including extramedullary disease, advanced-stage disease, and high tumor burden) continues to be associated with inferior outcomes, highlighting the need for precision medicine approaches and further evaluation of emerging immunotherapy strategies.

Reference: 
Gareth J. Morgan et al. High-Risk Multiple Myeloma: Redefining Risk and Rethinking Therapy. Am Soc Clin Oncol Educ Book 46, e517494(2026). DOI:10.1200/EDBK-26-517494  (https://ascopubs.org/doi/10.1200/EDBK-26-517494) 

Targeting BCMA in Patients with Relapsed/Refractory Multiple Myeloma in 1-3 Prior Lines of Therapy — Blood Advances (May 2026)

What is the purpose of the review? 
To examine the emerging role of B-cell maturation antigen (BCMA)-directed immunotherapies in patients with relapsed/refractory multiple myeloma (RRMM) who have received 1–3 prior lines of therapy. It summarizes evidence from recent phase 3 clinical trials and discusses how patient characteristics, disease features, treatment logistics, and access considerations may influence therapy selection.

Summary 
The review evaluates three major classes of BCMA-targeted therapies—antibody-drug conjugates (ADCs), chimeric antigen receptor (CAR) T-cell therapies, and bispecific T-cell engagers (TCEs)—that have recently been studied in early-relapse multiple myeloma. Clinical trial data showed improvements in progression-free survival (PFS) and response rates with agents such as belantamab mafodotin combinations, ciltacabtagene autoleucel (cilta-cel), idecabtagene vicleucel (ide-cel), and teclistamab-based regimens, although toxicity profiles, treatment administration, and patient eligibility differed across studies. The authors emphasize individualized treatment selection based on factors including age, frailty, comorbidities, disease biology, prior therapies, caregiver support, treatment accessibility, and patient preferences, while highlighting the importance of shared decision-making.

Key points

BCMA-directed therapies evaluated 
• Antibody-drug conjugates (ADCs): 
 - Belantamab mafodotin (belamaf) combinations improved progression-free survival and response rates in studies such as DREAMM-7 and DREAMM-8. 
 - Common adverse effects included thrombocytopenia and keratopathy, requiring ophthalmologic monitoring.

• CAR T-cell therapies: 
 - Cilta-cel was associated with prolonged progression-free survival in clinical trials, including a reported median PFS of 36.6 months and a 36-month PFS rate of approximately 57%. 
 - Ide-cel improved median PFS to 13.8 months in the reported study. 
 - Grade ≥3 cytokine release syndrome (CRS) occurred in approximately 1–4% of patients, and neurotoxicity occurred in approximately 5–15%.

• Bispecific T-cell engagers (TCEs): 
 - Teclistamab-based regimens were associated with improved outcomes in reported studies. 
 - Selected studies reported 3-year progression-free survival and overall survival rates of approximately 83%, although outcomes varied across studies and treatment regimens. 
 - Additional investigational agents include elranatamab, linvoseltamab, and etentamig. 
 - Grade ≥3 CRS occurred infrequently in reported studies. 

Factors Influencing treatment selection 
• Chronological age alone should not determine therapy choice. 
• Important considerations include: 
 - Frailty and physiologic fitness. 
 - Comorbidities and infection risk. 
 - Disease aggressiveness and tumor burden. 
 - Prior treatment exposure and refractoriness. 
 - Patient preferences and treatment goals. 
 - Availability of caregivers and proximity to treatment centers. 
 - Access to specialized cellular therapy programs.

Practical clinical considerations 
• CAR T-cell therapy is administered as a one-time treatment but requires specialized centers, manufacturing time, and intensive monitoring. 
• TCEs can often be administered in outpatient settings and have been used in older or medically complex patients. 
• ADCs may provide a less intensive treatment approach than cellular therapies but require monitoring for ocular toxicity. 
• The authors note that immediately available therapies such as TCEs may be considered for patients with rapidly progressing disease because CAR T-cell therapy requires manufacturing time.

Strengths 
• Provides a comprehensive synthesis of recent phase 3 clinical trial data across multiple BCMA-directed therapeutic classes. 
• Discusses treatment selection using clinical, patient-specific, and logistical considerations in addition to efficacy and safety outcomes. 
• Explores the applicability of available evidence to common clinical scenarios encountered in early-relapse multiple myeloma.

Limitations 
• This is a narrative review and does not report new clinical trial data. 
• Direct comparisons between therapies are limited because studies differed in patient populations, eligibility criteria, endpoints, follow-up duration, and trial design. 
• Real-world applicability may vary according to treatment availability, healthcare resources, and patient eligibility.

Why this review matters 
BCMA-directed therapies have increased the number of available treatment options for patients with relapsed/refractory multiple myeloma after 1–3 prior lines of therapy. Clinical trials have reported improvements in progression-free survival and response rates compared with standard regimens, but treatment selection remains dependent on patient characteristics, disease features, safety considerations, treatment logistics, and access. The review emphasizes individualized treatment selection and shared decision-making when choosing among BCMA-directed therapies.

Reference: 
Doris K Hansen, Maria-Victoria Mateos, Luciano J. Costa; Targeting BCMA in Patients with Relapsed/Refractory Multiple Myeloma in 1-3 Prior Lines of Therapy. Blood Adv 2026; bloodadvances.2026019699. doi: https://doi.org/10.1182/bloodadvances.2026019699 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2026019699/568812/Targeting-BCMA-in-Patients-with-Relapsed)

Research

 
Sustained MRD Negative for 4 Years Is a Significant Marker of Prognosis in Patients with High-Risk Multiple Myeloma — Cancers (May 2026)

What is the purpose of the study? 
To evaluate how the duration of sustained minimal residual disease (MRD) negativity influences prognosis in transplant-eligible newly diagnosed multiple myeloma (TE-NDMM), particularly in patients with high-risk cytogenetic abnormalities. It also seeks to identify a minimum duration of MRD negativity associated with progression-free survival (PFS) and overall survival (OS) outcomes.

Summary 
This single-center retrospective study included 223 TE-NDMM patients who achieved at least two consecutive MRD-negative assessments after initial treatment. High-risk patients who maintained MRD negativity for at least 2 years showed no statistically significant difference in PFS compared with standard-risk patients (70.77 vs. 67.38 months, p = 0.529), without evidence of equivalence between groups. In the overall cohort, MRD negativity duration >2 years was associated with superior overall survival. Exploratory analyses of longer durations (≥3 years in standard-risk and ≥4 years in high-risk patients) showed variable and non-significant differences in PFS across comparisons, with several results limited by small subgroup sizes.

Key points 
• Retrospective, single-center study of 223 TE-NDMM patients achieving sustained MRD negativity (sensitivity ~10⁻⁵). 
• Evaluated the relationship between MRD negativity duration and survival outcomes (PFS and OS) by a cytogenetic risk group. 
• In high-risk patients, ≥2 years of MRD negativity was associated with no statistically significant difference in PFS compared with standard-risk patients. 
• In the overall cohort, MRD negativity duration >2 years was associated with superior overall survival. 
• Longer MRD durations (≥3 years standard-risk; ≥4 years high-risk) showed non-significant and variable differences in PFS across exploratory subgroup analyses.

Strengths 
• Focus on duration of MRD negativity as a time-dependent prognostic variable rather than a single time-point assessment. 
• Stratification by cytogenetic risk (high-risk vs standard-risk multiple myeloma). 
• Use of clinically relevant endpoints including progression-free survival (PFS) and overall survival (OS). 
• Provides exploratory, hypothesis-generating evaluation of MRD dynamics over time.

Limitations 
• Retrospective, single-center design with potential selection bias and treatment heterogeneity. 
• Small subgroup sizes, particularly in long-duration MRD-negative cohorts (e.g., very limited ≥4-year high-risk group). 
• MRD assessment limited to ~10⁻⁵ sensitivity, with variability in testing schedules and methods. 
• Findings are exploratory and not validated for clinical decision-making. 
• Potential selection bias, as patients achieving prolonged MRD negativity may represent a biologically favorable subset.

Why this study matters 
Sustained MRD negativity was associated with improved survival outcomes in TE-NDMM, particularly in patients with high-risk cytogenetic abnormalities. MRD negativity duration >2 years was associated with superior overall survival in the overall cohort, while high-risk patients with ≥2 years of MRD negativity showed no statistically significant difference in progression-free survival compared with standard-risk patients. Longer durations of MRD negativity showed non-significant and variable associations with progression-free survival in exploratory analyses, and these findings require validation in larger prospective studies before clinical application.

Reference: 
Liu, H., Chen, M., Li, X., Kuang, L., Li, J., Li, Y., & Li, J. (2026). Sustained MRD Negative for 4 Years Is a Significant Marker of Prognosis in Patients with High-Risk Multiple Myeloma. Cancers, 18(10), 1569. https://doi.org/10.3390/cancers18101569 (https://www.mdpi.com/2072-6694/18/10/1569)

Triplet or Quadruplet Regimen Utilization and Overall Survival in Patients Diagnosed With Multiple Myeloma Between 2017 and 2023 — eJHaem (May 2026)

What is the purpose of the study? 
To evaluate the uptake of triplet or quadruplet therapy among patients with newly diagnosed multiple myeloma (NDMM) in routine clinical practice between 2017 and 2023, and to examine sociodemographic and clinical factors associated with treatment selection and overall survival (OS). The study also assesses real-world 5-year survival outcomes using electronic health record and mortality data from a large integrated healthcare system.

Summary 
In this retrospective cohort study, researchers analyzed 1,230 adults diagnosed with NDMM across Ohio and Florida between 2017 and 2023. Within 1 year of diagnosis, 57.5% of patients received triplet or quadruplet therapy, with utilization increasing from 57.1% in 2017 to 65.9% in 2023. The authors also noted that quadruplet regimens surpassed triplet regimens during 2023–2024 treatment trends discussed in the study. Older age, residence in more socioeconomically disadvantaged neighborhoods, and treatment at a Florida regional hospital were associated with lower odds of receiving triplet or quadruplet therapy, while poorer kidney function, higher comorbidity burden, treatment at an Ohio regional hospital, and diagnosis in 2023 were associated with higher odds. The estimated 5-year OS for the cohort was 62.1% (95% CI, 59.0%–65.4%), which appeared higher than historical survival estimates reported from 2000–2008.

Key points 
• Study population: 1,230 adults with newly diagnosed multiple myeloma diagnosed between 2017 and 2023. 
• Treatment uptake: 57.5% received triplet or quadruplet therapy within 1 year of diagnosis. 
• Trends over time: Use of combination therapy increased during the study period, and the authors reported that quadruplet regimens surpassed triplet regimens in treatment trends observed during 2023–2024. 
• Factors associated with lower treatment use: 
 - Older age 
 - Residence in more disadvantaged neighborhoods 
 - Treatment at a Florida regional hospital versus Taussig Cancer Center

• Factors associated with higher treatment use: 
 - Diagnosis in 2023 
 - Reduced kidney function (eGFR <60) 
 - Charlson Comorbidity Index ≥3 
 - Treatment at an Ohio regional hospital

• Survival outcomes: Estimated 5-year OS was 62.1% (95% CI, 59.0%–65.4%), compared with historical reports ranging from 31%–50%. 
• Possible contributors discussed by the authors: Financial burden, logistical barriers, and differences between clinical trial populations and real-world patients may influence treatment uptake and outcomes.

Strengths 
• Large and diverse real-world patient cohort. 
• Included multiple treatment locations and insurance types. 
• Long follow-up through 2025 using electronic health records and linked death records. 
• Captured treatment trends during a period of evolving multiple myeloma therapies.

Limitations 
• Conducted within a single healthcare system, which may limit generalizability. 
• Could not assess reasons for treatment refusal, delay, or clinician decision-making. 
• Some treatments received in clinical trials or outside facilities may not have been captured. 
• Limited availability of detailed prognostic clinical markers. 
• Treatment regimens could change over time, which may affect classification.

Why this study matters 
This real-world study found that use of triplet and quadruplet therapy for NDMM increased between 2017 and 2023, although treatment utilization differed according to age, socioeconomic status, treatment location, and clinical factors. The cohort’s estimated 5-year overall survival appeared higher than previously reported historical estimates, reflecting changes in treatment patterns over time. The findings also highlight potential disparities and practical barriers that may affect access to newer combination therapies in routine clinical practice.

Reference: 
E. R. Wesley, F. Anwer, M.B. Rothberg, et al. “Triplet or Quadruplet Regimen Utilization and Overall Survival in Patients Diagnosed With Multiple Myeloma Between 2017 and 2023.” eJHaem7, no. 3 (2026): e70309. https://doi.org/10.1002/jha2.70309 (https://onlinelibrary.wiley.com/doi/10.1002/jha2.70309)

Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma — Transplantation and Cellular Therapy (May 2026)

What is the purpose of the study? 
To evaluate clinical outcomes, CAR T-cell kinetics, and toxicity in patients with relapsed/refractory multiple myeloma (RRMM) treated with idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel). It examines the impact of chronic kidney disease (CKD) severity and lymphodepletion regimens (fludarabine/cyclophosphamide [Flu/Cy] versus bendamustine) on progression-free survival (PFS), overall survival (OS), immune cell dynamics, and treatment-related toxicity.

Summary 
The retrospective study included 87 patients, of whom 53 had none/mild CKD and 34 had moderate/severe CKD. CKD status alone was not significantly associated with OS or PFS, and lymphodepletion regimen was not independently associated with PFS in survival analyses. However, a significant interaction was observed between CKD status and CAR T-cell product, indicating that the effect of treatment differed by kidney function. In subgroup analyses, Cilta-cel was associated with significantly improved PFS compared with Ide-cel in patients with none/mild CKD, whereas no significant benefit was observed in patients with moderate/severe CKD. CAR T-cell expansion kinetics overall did not differ by CKD status or lymphodepletion regimen, although patients with none/mild CKD receiving Cilta-cel demonstrated significantly higher proportions of CD4 CAR T cells within the CD3 CAR T-cell population at days 7, 14, and 30 compared with Ide-cel recipients. Bendamustine-based lymphodepletion was used more frequently in patients with moderate/severe CKD and was associated with a later ALC nadir and higher ALC at infusion compared with full-dose Flu/Cy, along with lower early non–immune effector cell–associated hematotoxicity (N-ICAHT), higher absolute neutrophil count (ANC) nadirs, and similar rates of cytokine release syndrome (CRS) and ICANS.

Key points 
• Study included 87 RRMM patients treated with Ide-cel or Cilta-cel. 
• CKD status alone was not significantly associated with OS or PFS. 
• A statistically significant interaction was observed between CKD status and CAR T-cell product. 
• Cilta-cel showed improved PFS vs Ide-cel only in none/mild CKD, with no significant difference in moderate/severe CKD. 
• Overall, CAR T-cell expansion kinetics were not significantly different by CKD status or lymphodepletion regimen. 
• In none/mild CKD, Cilta-cel was associated with higher CD4 CAR T-cell proportions at days 7, 14, and 30 compared with Ide-cel. 
• Lymphodepletion regimen was not independently associated with PFS. 
• Bendamustine-based lymphodepletion was associated with: 
 - More frequent use in moderate/severe CKD patients 
 - Higher ALC at infusion and different ALC nadir timing compared with Flu/Cy 
 - Lower early N-ICAHT 
 - Higher ANC nadirs 
 - Similar CRS and ICANS rates vs Flu/Cy

Strengths 
• Detailed clinical and immunologic dataset with extensive longitudinal sampling (>2,000 patient-days and >20,000 data points). 
• Concurrent evaluation of clinical outcomes, CAR T-cell kinetics, and toxicity. 
• Inclusion of a clinically relevant RRMM population with varying degrees of renal impairment.

Limitations 
• Retrospective, non-randomized design limits causal inference. 
• Small sample size for bendamustine subgroup (n=9), limiting precision. 
• Significant subgroup findings may be influenced by confounding (e.g., baseline frailty, treatment selection based on renal function). 
• Wide confidence interval for the CKD–CAR T product interaction indicates uncertainty in effect size.

Why this study matters 
In this retrospective study of CAR T-cell therapy in RRMM, CKD status alone was not significantly associated with survival outcomes. However, a statistically significant interaction between CKD status and CAR T-cell product suggests that treatment effect differed by renal function, with cilta-cel showing improved PFS compared with ide-cel only in patients with none/mild CKD. Bendamustine-based lymphodepletion was associated with distinct hematologic and immune effects but did not significantly impact PFS. Overall, the findings indicate that both renal function and CAR T-cell product may influence outcomes, though several subgroup findings are limited by sample size and statistical uncertainty.

Reference: 
Nora Grieb, Thomas Wiemers, Patrick Born, David Fandrei, Luise Fischer, Maximilian Ferle, Stefan Franke, Johannes Keller, Song Yau Wang, Madlen Jentzsch, Carmen Herling, Klaus H. Metzeler, Marco Herling, Simone Heyn, Thomas Neumuth, Uwe Platzbecker, Vladan Vučinić, Georg-Nikolaus Franke, Maximilian Merz, Impact of Renal Impairment and Lymphodepletion Regimen on Outcomes after CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma, Transplantation and Cellular Therapy, 2026, ISSN 2666-6367, https://doi.org/10.1016/j.jtct.2026.05.022. (https://www.sciencedirect.com/science/article/pii/S2666636726004112?via%3Dihub)

Real-world outcomes of melflufen plus dexamethasone in heavily pretreated relapsed/refractory multiple myeloma after exposure to immunotherapies — Clinical Lymphoma Myeloma and Leukemia (May 2026)

What is the purpose of the study? 
To evaluate the effectiveness and safety of melphalan flufenamide plus dexamethasone (melf-dex) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM), including those previously treated with BCMA- and/or GPRC5D-directed immunotherapies. The study aims to assess outcomes outside clinical trials in a population with limited remaining treatment options.

Summary 
In this retrospective real-world study, data were collected from 19 patients with RRMM treated at 8 Spanish institutions between June 2024 and May 2025. Patients had received a median of 5 prior treatment lines, and most were triple-class refractory (95%), penta-class refractory (74%), and previously exposed to BCMA/GPRC5D-targeted therapies (74%). Melf-dex achieved an overall response rate (ORR) of 28% (5/18 evaluable patients) in the overall cohort and 33% (4/12) in the immunotherapy-exposed subgroup, with stable disease rates of 44% and 42%, respectively. Median progression-free survival (PFS) was 4.8 months (95% CI: 2.5–not reached).

Grade 3 or higher hematologic toxicities were common, including thrombocytopenia (68%), neutropenia (68%), and anemia (47%). Infections occurred in 10 patients, mostly grade 1–2, although one patient discontinued treatment because of severe thrombocytopenia and bleeding, and one patient died from sepsis. At a median follow-up of 5.75 months, median overall survival had not been reached, and three patients remained alive and responding beyond nine months.

Key points 
• First reported real-world series evaluating melf-dex after exposure to BCMA- and/or GPRC5D-directed immunotherapies in RRMM
• Included 19 heavily pretreated patients treated across 8 Spanish centers
• Median prior therapies: 5 lines. 
• High-risk disease characteristics: 
 - 95% triple-class refractory
 - 74% penta-class refractory 
 - 74% previously exposed to anti-BCMA/GPRC5D therapies

• Efficacy outcomes: 
 - ORR: 28% (5/18 evaluable patients) overall
 - ORR: 33% (4/12) in immunotherapy-exposed subgroup
 - Stable disease: 44% overall. 
 - Median PFS: 4.8 months (95% CI: 2.5–not reached)

• Safety findings: 
 - Grade ≥3 thrombocytopenia: 68%
 - Grade ≥3 neutropenia: 68% 
 - Grade ≥3 anemia: 47% 
 - Infections reported in 10 patients, mostly grade 1–2
 - One treatment discontinuation due to thrombocytopenia and bleeding
 - One death related to sepsis

Strengths
• Real-world multicenter data
• Included patients previously treated with newer immunotherapies
• Provides additional data in a difficult-to-treat population

Limitations
• Small sample size (19 patients) 
• Retrospective study design
• Short follow-up duration
• No comparator/control group

Why this study matters 
In this retrospective real-world study, melf-dex achieved an ORR of 28% and median PFS of 4.8 months in heavily pretreated RRMM, including patients previously exposed to BCMA- and GPRC5D-directed therapies. Hematologic toxicities and infections were common, including one treatment-related discontinuation and one death from sepsis. Larger studies with longer follow-up are needed to better characterize outcomes in this setting.

Reference: 
David Martínez-Campuzano, Clara Sopeña, María José Moreno, María Sánchez, Adriana Gascón, Pablo Lorente, Mario Montagud, Jaime Pascual Martí, Silvina Ríos, Mario Arnao, Javier de la Rubia, Real-world outcomes of melflufen plus dexamethasone in heavily pretreated relapsed/refractory multiple myeloma after exposure to immunotherapies, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.05.002. (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(26)00145-X/abstract)

Condensed vs. Standard Step-Up Dosing Schedule of Talquetamab in Relapsed/Refractory Multiple Myeloma — European Journal of Haematology (May 2026)

What is the purpose of the study? 
To compare the incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between standard and condensed step-up dosing (SUD) schedules of talquetamab in patients with relapsed/refractory multiple myeloma (RRMM).

Summary 
In this multicenter retrospective study, researchers analyzed 144 patients treated with talquetamab across seven academic medical centers in the U.S. Thirty-three patients received the standard SUD schedule (Days 1, 4, 7, and 10) and 111 received the condensed SUD schedule (Days 1, 3, 5, and 7). CRS occurred in 76% of patients receiving the standard schedule and 56% receiving the condensed schedule (p = 0.101), while ICANS occurred in 9% and 16% of patients, respectively (p = 0.41). No statistically significant differences were observed in the incidence or severity of CRS or ICANS between the two dosing schedules.

Key points 
• Retrospective multicenter study including 144 patients with RRMM 
• Compared two talquetamab step-up dosing schedules: 
 - Standard SUD: Days 1, 4, 7, and 10 
 - Condensed SUD: Days 1, 3, 5, and 7

• CRS incidence: 
 - Standard SUD: 76% 
 - Condensed SUD: 56% 
 - p = 0.101

• ICANS incidence: 
 - Standard SUD: 9% 
 - Condensed SUD: 16% 
 - p = 0.41

• No statistically significant differences in the severity of CRS or ICANS between cohorts

Why this study matters 
In this multicenter retrospective study of patients with RRMM, condensed talquetamab step-up dosing was associated with no statistically significant differences in the incidence or severity of CRS or ICANS compared with the standard schedule. These findings suggest that shortening the interval between talquetamab step-up doses may be feasible in routine clinical practice.

Reference: 
G. Elsey, J. A. Davis, K. Julian, et al., “Condensed vs. Standard Step-Up Dosing Schedule of Talquetamab in Relapsed/Refractory Multiple Myeloma,” European Journal of Haematology (2026): 1–6, https://doi.org/10.1111/ejh.70221 (https://onlinelibrary.wiley.com/doi/10.1111/ejh.70221).

Real-World Evaluation of Talquetamab for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): An International Myeloma Working Group Immunotherapy Registry Real-World Analysis — American Journal of Hematology (May 2026)

What is the purpose of the study? 
To evaluate the safety, muco-cutaneous toxicities, infections, and effectiveness of talquetamab in patients with relapsed/refractory multiple myeloma (RRMM), including patients with substantial prior treatment exposure and comorbidities who may not have qualified for the pivotal MonumenTAL-1 trial. The study was conducted across academic centers in the United States, United Kingdom, Greece, Spain, and Canada through the International Myeloma Foundation (IMF) Immunotherapy Database Protocol with participation from members of the International Myeloma Working Group (IMWG) Immunotherapy Committee.

Summary 
This real-world, retrospective international multicenter study included 151 patients with RRMM treated with talquetamab at nine academic centers across the United States, United Kingdom, Greece, Spain, and Canada between 2022 and 2025. The study was coordinated within the International Myeloma Foundation Immunotherapy Database Protocol and involved collaboration among investigators from the International Myeloma Working Group Immunotherapy Committee. Patients were heavily pretreated, with a median of 6 prior lines of therapy, 53% classified as penta-refractory, and 75% previously exposed to BCMA-directed therapy. More than half (55%) would not have met eligibility criteria for the MonumenTAL-1 trial.

With a median follow-up of 12.7 months, the overall response rate (ORR) was 67.6%, median progression-free survival (PFS) was 7 months, and 12-month overall survival was 65%. Common toxicities included nail changes (75.5%), oral toxicities (62.9%), dysgeusia (60.4%), and skin toxicities (39.7%), although grade ≥3 events were uncommon (≤4%), and treatment discontinuation due to adverse events was infrequent. Infection-related hospitalizations occurred in 24% of patients and were used as a marker of severe infection in this retrospective analysis, while opportunistic infections and infection-related deaths were rare.

Key points 
• Largest reported international real-world cohort of talquetamab-treated RRMM patients (151 patients)
• Conducted across 9 academic centers in 5 countries: United States, United Kingdom, Greece, Spain, and Canada 
• Organized through the International Myeloma Foundation Immunotherapy Database Protocol with collaboration from the International Myeloma Working Group Immunotherapy Committee 
• Median follow-up: 12.7 months. 
• Patient population was clinically complex: 
 - 42% had high-risk cytogenetics. 
 - 22% had ECOG performance status ≥2. 
 - 12% had creatinine clearance <30. 
 - 55% were ineligible for MonumenTAL-1 criteria

• Treatment history: 
 - Median of 6 prior lines of therapy 
 - 53% penta-refractory 
 - 75% had prior BCMA-targeted therapy exposure

• Efficacy outcomes: 
 - Overall response rate (ORR): 67.6%
 - ≥VGPR: 49%
 - CR/sCR: 19%
 - Median PFS: 7 months
 - 12-month overall survival: 65%

• Common adverse events: 
 - Nail toxicity: 75.5%
 - Oral toxicities: 62.9%
 - Dysgeusia: 60.4%
 - Skin toxicity: 39.7%

• Severe toxicities (grade ≥3) were uncommon (≤4%). 
• Infection findings: 
 - 51% experienced at least one infection
 - Infection-related hospitalization occurred in 24%
 - Opportunistic infections and CMV organ disease were rare
 - No infection-related deaths were reported

• Multivariable analysis: 
 - Platelet count <50 × 10⁹/L was associated with worse PFS (HR 1.8; 95% CI 1.15–2.83)
 - Prior BCMA therapy, penta-refractory status, and low absolute lymphocyte count were not significantly associated with inferior PFS

Strengths 
• Large multinational real-world cohort spanning five countries
• Longer follow-up than prior real-world analyses
• Included patients with significant comorbidity burden and prior BCMA exposure, improving generalizability to routine clinical practice
• International collaboration through IMF and IMWG enhanced data collection and peer-based quality review

Limitations 
• Retrospective study design
• No centralized response assessment
• Non-standardized toxicity grading across centers
• Limited data on IVIG use, vaccination status, weight loss, ataxia, and detailed BCMA exposure history
• Possible under-reporting of complete responses due to infrequent bone marrow confirmation.

Why this study matters 
In this multinational real-world cohort conducted across the United States, United Kingdom, Greece, Spain, and Canada, talquetamab demonstrated clinical activity in heavily pretreated RRMM patients, including many with prior BCMA-directed therapy and substantial comorbidity burden. The study, conducted through collaboration between the International Myeloma Foundation and International Myeloma Working Group investigators, found that response rates and survival outcomes were broadly comparable to those reported in the MonumenTAL-1 trial despite differences in patient characteristics, while muco-cutaneous toxicities and infections remained common but generally manageable. These findings support the need for continued supportive care strategies to address oral, nail, skin, and taste-related adverse effects during treatment.

Reference: 
M. Janakiram, C. R. Tan, H. Mian, et al., “Real-World Evaluation of Talquetamab for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM): An International Myeloma Working Group Immunotherapy Registry Real-World Analysis,” American Journal of Hematology (2026): 1–10, https://doi.org/10.1002/ajh.70376. (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70376)

 
Comparative economic analysis of B-cell maturation antigen-targeted bispecific antibodies in triple-class exposed relapsed/refractory multiple myeloma: linvoseltamab versus teclistamab and elranatamab — Current Medical Research and Opinion (May 2026)

What is the purpose of the study? 
To evaluate total cost of care, average monthly treatment cost, and cost per clinical outcome of linvoseltamab versus teclistamab and elranatamab in triple-class-exposed relapsed/refractory multiple myeloma (RRMM). The analysis uses matching-adjusted indirect comparisons (MAICs) over 1- and 2-year time horizons from a U.S. commercial payer perspective, applying label-based dosing and trial-informed clinical inputs.

Summary  
Costs and outcomes were estimated using MAIC-adjusted efficacy data and modeled treatment duration, incorporating drug acquisition, administration, monitoring, adverse event, progression, and death-related costs. Linvoseltamab had lower total costs than teclistamab at 1 year ($387,773 vs $500,670) and 2 years ($488,088 vs $639,013), with lower cost per progression-free month and per overall response across both time points. Compared with elranatamab, linvoseltamab had lower total costs at 1 year ($383,368 vs $416,359) and similar total costs at 2 years ($472,907 vs $475,918), with lower or comparable cost per outcome measures across reported endpoints.

Key points

Strengths 
• Incorporates multiple cost components including drug acquisition, administration, monitoring, adverse event management, progression, and death
• Uses MAIC-adjusted clinical inputs derived from published trials in the absence of head-to-head comparisons
• Applies label-based dosing schedules, including response-adapted dosing where applicable
• Includes scenario analyses exploring alternative assumptions for treatment duration and care setting

Limitations 
• Reliance on unanchored MAICs, which adjust only for observed characteristics and do not account for unmeasured confounding
• Reduced effective sample size due to weighting, contributing to uncertainty in estimates 
• No direct randomized comparisons; results are not intended as formal comparative effectiveness evidence
• Differences in trial design, follow-up, and dosing assumptions may affect comparability across treatments
• Infection timing assumptions (particularly for elranatamab) and other structural modeling inputs introduce uncertainty
• AE-related and progression-related cost estimates are dependent on limited or aggregated data and model assumptions

Why this comparative analysis matters 
In this model-based economic evaluation, linvoseltamab showed lower total costs than teclistamab and similar total costs compared with elranatamab at 2 years under base-case assumptions. Cost per outcome estimates were lower for linvoseltamab versus teclistamab and generally similar or lower versus elranatamab across reported endpoints. Findings are based on indirect comparisons and model assumptions and therefore require cautious interpretation and validation with real-world data.

Reference: 
Portuguese, A. J., Inocencio, T. J., Quon, P., Harnett, J., Zhou, Z. Y., Hazra, N. C., … Ma, Q. (2026). Comparative economic analysis of B-cell maturation antigen-targeted bispecific antibodies in triple-class exposed relapsed/refractory multiple myeloma: linvoseltamab versus teclistamab and elranatamab. Current Medical Research and Opinion, 1–13. https://doi.org/10.1080/03007995.2026.2665022 (https://www.tandfonline.com/doi/full/10.1080/03007995.2026.2665022#abstract)

Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis — Journal of Hematology and Oncology (May 2026)

What is the purpose of the study? 
To evaluate real-world outcomes of standard-of-care ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with relapsed or refractory multiple myeloma (RRMM) treated earlier in their disease course (after 1–3 prior lines of therapy) compared with later-line use. The analysis aims to assess progression-free survival (PFS), response rates, and safety outcomes outside of clinical trials.

Summary 
Researchers analyzed data from 606 patients with RRMM treated with cilta-cel between 2022 and 2025 through the German Registry for Stem Cell Transplantation and Cellular Therapy. Patients were grouped based on prior treatment exposure into an Early group (1–3 prior lines; 177 patients) and a Late group (>3 prior lines; 429 patients). Overall response rates were high in both groups (91% Early; 88% Late), with complete responses observed in 63% and 54% of patients, respectively. Twelve-month PFS was 79% in the Early group and 70% in the Late group, while patients who maintained complete response had 100% PFS at 12 months regardless of treatment line.

Extramedullary disease was associated with poorer outcomes in both groups, whereas high-risk cytogenetic abnormalities did not appear to reduce PFS in earlier-line patients. Non-ICANS neurotoxicity occurred less often in earlier-line treatment (3% vs 8%), while non-relapse mortality was similar between groups (6% vs 7%). The findings were consistent with results previously reported in the phase 3 CARTITUDE-4 trial.

Key points 
• Study included 606 patients with relapsed or refractory multiple myeloma treated with cilta-cel in routine clinical practice 
• Patients treated earlier (1–3 prior lines) had: 
 - 91% overall response rate 
 - 63% complete response rate 
 - 79% 12-month progression-free survival

• Patients treated later (>3 prior lines) had: 
 - 88% overall response rate 
 - 54% complete response rate 
 - 70% 12-month progression-free survival

• Maintaining a complete response was strongly associated with prolonged PFS in both groups 
• Extramedullary disease was linked to worse outcomes across treatment settings 
• High-risk cytogenetics were not associated with inferior PFS in the Early treatment group
• Non-ICANS neurotoxicity occurred less frequently with earlier-line use (3% vs 8%) 
• Non-relapse mortality was similar between groups (6% vs 7%).

Strengths 
• Large real-world dataset from a national registry 
• Included patients treated outside controlled clinical trial settings 
• Direct comparison of earlier- versus later-line use of cilta-cel

Limitations 
• Observational registry study without randomized treatment assignment 
• Follow-up duration may be limited for assessing long-term outcomes. 
• Potential differences in baseline characteristics between Early and Late groups could affect comparisons.

Why this study matters 
This real-world analysis found that cilta-cel produced high response rates and durable progression-free survival in patients with relapsed or refractory multiple myeloma, including those treated after only 1–3 prior lines of therapy. Earlier-line treatment was associated with deeper responses and somewhat lower rates of non-ICANS neurotoxicity, while safety outcomes overall were broadly comparable between groups. The results support the feasibility and effectiveness of cilta-cel use earlier in the treatment course and are consistent with findings from the CARTITUDE-4 clinical trial.

Reference: 
Gagelmann, N., Einsele, H., Flossdorf, S. et al. Standard-of-care ciltacabtagene autoleucel in earlier versus later lines of therapy for relapsed or refractory multiple myeloma: a nationwide registry analysis. J Hematol Oncol (2026). https://doi.org/10.1186/s13045-026-01806-6 (https://link.springer.com/article/10.1186/s13045-026-01806-6)

 
Machine Learning Model Predicts Monoclonal Gammopathy Using Routine Laboratory Values — JCO Clinical Cancer Informatics (May 2026)

What is the purpose of the study? 
To evaluate whether routine laboratory data could be used to develop a machine learning (ML) model to predict the presence of monoclonal protein (M-protein) associated with monoclonal gammopathy (MG), including monoclonal gammopathy of undetermined significance (MGUS) and plasma cell myeloma (PCM). The goal was to support earlier recognition of patients at risk for MG using routinely collected clinical laboratory data.

Summary 
Researchers analyzed 7 years of longitudinal laboratory data from 232,813 adults in a large US outpatient network and developed an ML-based risk classifier using XGBoost. The final seven-variable model predicted the presence of M-protein within 5 years and achieved an area under the curve (AUC) of 0.84. Key predictors included absolute lymphocyte count trajectory, age, red blood cell (RBC) count, total protein, red cell distribution width (RDW), blood urea nitrogen (BUN), and relative eosinophil levels. The model used routinely available complete blood count and metabolic panel variables and was developed within a higher-risk outpatient population undergoing protein electrophoresis testing.

Key points 
• Retrospective cohort study using deidentified real-world laboratory data from 232,813 US outpatients
• Included 1,610 patients aged 50–85 years with: 
 - ≥3 complete blood count and metabolic panel results 
 - ≥1 protein electrophoresis test

• ML model developed using XGBoost to predict M-protein associated with MG
• Seven-variable classifier achieved: 
 - AUC: 0.84 
 - Prediction window: up to 5 years before M-protein detection

• Most important predictors: 
 - Absolute lymphocyte count trajectory 
 - Age 
 - RBC count 
 - Total protein 
 - RDW 
 - BUN 
 - Relative eosinophils

• Median laboratory values for several predictors remained within standard reference ranges, suggesting the model may detect subtle laboratory differences associated with early-stage MG
• The study evaluated prediction of positive M-protein rather than clinically confirmed MG diagnoses

Strengths 
• Large and geographically diverse US outpatient cohort
• Use of longitudinal real-world laboratory data
• Model based on routinely available laboratory tests, supporting potential scalability and clinical usability
• Included potentially undiagnosed MG cases, which may improve applicability to community populations

Limitations 
• MG classification was based primarily on positive M-protein laboratory findings rather than established clinical diagnoses. 
• The model did not capture light-chain MGUS cases without detectable heavy-chain M-protein. 
• The cohort may have been enriched for higher-risk individuals because protein electrophoresis testing was performed based on clinical suspicion, introducing potential selection bias. 
• Clinical variables such as imaging findings, family history, environmental exposures, body weight, and molecular-cytogenetic abnormalities were not included. 
• Prospective validation studies are needed before broader clinical implementation.

Why this study matters 
This retrospective study developed a machine learning classifier using routine laboratory variables to predict the presence of M-protein associated with monoclonal gammopathy, achieving an AUC of 0.84. The model identified several laboratory and demographic predictors, including absolute lymphocyte count trajectory, age, RBC count, and total protein. Although the findings support the potential role of routine laboratory data in MG risk prediction, prospective validation and evaluation in broader clinical populations are needed.

Reference: 
Mercedeh Movassagh et al. Machine Learning Model Predicts Monoclonal Gammopathy Using Routine Laboratory Values. JCO Clin Cancer Inform 10, e2600013(2026). DOI:10.1200/CCI-26-00013 (https://ascopubs.org/doi/10.1200/CCI-26-00013)

Mitigating Teclistamab Toxicity: Prophylactic Tocilizumab and Timing of Immunoglobulin Replacement Therapy in a Nationwide Cohort — American Journal of Hematology (May 2026)

What is the purpose of the study? 
This retrospective observational ABCD study evaluates real-world outcomes of teclistamab in relapsed or refractory multiple myeloma (RRMM) in Denmark, focusing on cytokine-release syndrome (CRS) prevention using prophylactic tocilizumab and infection outcomes in relation to immunoglobulin replacement therapy (IgRT).

Summary  
A nationwide cohort of 105 consecutively treated RRMM patients receiving teclistamab was analyzed, comparing 53 patients who received prophylactic tocilizumab before step-up dosing (PPxToci) with 52 patients who did not (NoPPxToci). Prophylactic tocilizumab was associated with a lower observed incidence of CRS (7–8% vs 69%) and reduced Grade 2 CRS (2% vs 29%), with no observed differences in ICANS, reported infection rates, or documented treatment efficacy outcomes between groups. Overall infection burden remained high (65% any grade; 31% Grade ≥3), and IgRT timing showed differing infection-free survival across subgroups, although interpretation is limited by potential baseline risk differences and non-randomized treatment allocation.

Key points 
• Study design: Retrospective, nationwide observational cohort (Denmark); 105 RRMM patients treated with teclistamab. 
• CRS outcomes: Prophylactic tocilizumab was associated with a substantially lower observed rate of CRS and fewer Grade 2 events compared with no prophylaxis. 
• Neurologic toxicity: ICANS was uncommon and similar between groups; all reported cases were Grade 1. 
• Infections: High infection burden overall (65% any grade; 31% Grade ≥3, including fatal events) with no clear between-group difference. 
• IgRT findings: Earlier or prior IgRT use was associated with longer Grade ≥3 infection-free survival, but interpretation is limited by confounding by indication and baseline risk differences. 
• Treatment efficacy: No statistically significant differences in efficacy endpoints were observed between groups, though the study was not powered for comparative efficacy assessment.

Strengths 
• Nationwide, unselected real-world cohort including all consecutive patients 
• Standardized toxicity grading (CTCAE v5.0, ASTCT criteria) 
• Direct comparison of centers with differing prophylactic tocilizumab practices (natural variation in implementation)

Limitations 
• Retrospective, non-randomized design with potential confounding and selection bias 
• Unequal follow-up duration between groups 
• Heterogeneous infection risk profiles and IgRT timing strategies 
• Limited ability to infer causality for observed associations

Why this study matters 
In this Danish real-world cohort, prophylactic tocilizumab administered before teclistamab step-up dosing was associated with a lower observed incidence of CRS, without detectable differences in infection rates or treatment efficacy outcomes. However, the non-randomized design and baseline differences between groups limit causal interpretation of these associations. Infection burden remained substantial overall, and outcomes related to IgRT suggest possible benefit of earlier initiation, though these findings are influenced by confounding factors and require further prospective evaluation.

Reference: 
A. H.Torpe, J.Thorsen, G.Mathiasen, et al., “Mitigating Teclistamab Toxicity: Prophylactic Tocilizumab and Timing of Immunoglobulin Replacement Therapy in a Nationwide Cohort,” American Journal of Hematology (2026): 1–5, https://doi.org/10.1002/ajh.70383 (https://onlinelibrary.wiley.com/doi/10.1002/ajh.70383).

Comparison of patient, hospitalization and center characteristics from the EMMY centers, IFM centers, and all multiple myeloma centers in France — Clinical Hematology International (May 2026)

What is the purpose of the study? 
To evaluate whether patients, hospitalizations, and treatment centers included in the French Epidemiology of Multiple MYeloma (EmmY) cohort are comparable to those treated in the French-speaking Intergroupe Francophone du Myélome (IFM) network and across all multiple myeloma (MM) treatment centers in France. The goal is to assess whether the EmmY cohort is a valid real-world data source for studying MM outcomes and care patterns.

Summary 
Researchers analyzed French national hospital discharge data (PMSI) from August 2017 to December 2023, identifying 69,276 adults hospitalized with MM, including 50,243 treated in IFM centers and 33,785 treated in EmmY centers. Because the analysis was based on hospitalization records, the findings reflect hospitalized MM patients and may not capture all patients managed exclusively in outpatient settings.

The study compared patient characteristics, comorbidities, hospitalization patterns, treatment-related factors, and center characteristics across EmmY centers, IFM centers, and all MM centers in France. No clinically meaningful differences were observed between EmmY and IFM populations with respect to age, sex, comorbidity burden, treatment patterns, or hospitalization outcomes. Although EmmY centers were generally larger and treated a higher proportion of MM patients than the average French MM center, overall patient and hospitalization characteristics were highly comparable, supporting the use of EmmY as a valid and broadly comparable real-world cohort for MM research.

Key points

Study population and data 
• Included 69,276 patients hospitalized with MM in France between 2017 and 2023. 
• Data were obtained from the French national hospital discharge database (PMSI). 
• Evaluated: 33,785 patients treated in EmmY centers. 50,243 patients treated in IFM centers. 323 MM treatment centers, including 70 EmmY and 118 IFM centers. 
• Based on 1,871,369 hospitalizations

Main findings 
• EmmY centers were larger and had a higher concentration of MM patients: 
 - EmmY: 2.7% MM patients per center. 
 - IFM: 2.4%. 
 - All MM centers: 1.3%.

• No clinically meaningful differences were observed between EmmY and IFM populations for age, sex, comorbidity burden, treatment patterns, and hospitalization outcomes

• Only a minor hospitalization difference was observed: 
 - Slightly more patients from general MM centers were discharged via transfer
 - Absolute difference was approximately 0.3%

Relevance to real-world evidence 
• More than 20% of hospitalized MM patients were over 80 years old, a population frequently underrepresented in randomized controlled trials (RCTs). 
• The study supports the value of observational cohorts for evaluating outcomes in older patients and patients with comorbidities who may not meet RCT eligibility criteria.

Strengths 
• Large national dataset covering more than six years. 
• Inclusion of a broad population of hospitalized MM patients treated in routine clinical practice. 
• Standardized patient identification using national hospital records. 
• Ability to evaluate populations often underrepresented in clinical trials. 
• Relatively homogeneous treatment environment in France, which may reduce variation in therapeutic pathways.

Limitations 
• Included only patients hospitalized for MM; patients managed exclusively in outpatient settings were not captured. 
• Hospitalization-based identification may underestimate the total MM population. 
• Cross-sectional comparisons may not fully capture changes over time. 
• The analysis compared patients treated in EmmY centers rather than only those formally enrolled in the ongoing EmmY cohort.

Why this study matters 
This nationwide analysis found that patients treated in EmmY centers were highly comparable to those treated in IFM centers and across the broader French MM treatment landscape, despite EmmY centers being larger and more specialized. These findings support the validity of EmmY as a robust real-world data source for studying treatment pathways and outcomes in multiple myeloma, including older and comorbid patients who are often underrepresented in randomized clinical trials. The study also highlights the importance of large observational cohorts in complementing clinical trial evidence and improving understanding of real-world MM care.

Reference: 
Olivier D, Garlantezec, R, Perrot, A, et al. Comparison of patient, hospitalization and center characteristics from the EMMY centers, IFM centers, and all multiple myeloma centers in France. Clinical Hematology International. 2026;8(2):50-58. doi:10.46989/001c.161361  (https://chi.scholasticahq.com/article/161361-comparison-of-patient-hospitalization-and-center-characteristics-from-the-emmy-centers-ifm-centers-and-all-multiple-myeloma-centers-in-france) 

Real-World Incidence and Management of Non-Immune Effector Cell-Associated Neurotoxicity Syndrome Neurologic Events Following Ciltacabtagene Autoleucel in Multiple Myeloma — Clinical Epidemiology (May 2026)

What is the purpose of the study? 
To evaluate the incidence, management, and outcomes of non-immune effector cell-associated neurotoxicity syndrome (non-ICANS) neurologic events in patients with relapsed/refractory multiple myeloma (RRMM) treated with ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T therapy. It also described post-infusion absolute lymphocyte count (ALC) patterns in patients with and without these neurologic events.

Summary 
Electronic medical record data from 171 adults with RRMM treated with cilta-cel between February 2022 and May 2025 were analyzed using data from the Loopback Analytics database, supplemented with physician notes. Patients were grouped by prior lines of therapy (1–3 LOT and ≥4 LOT). The study assessed new-onset non-ICANS neurologic events, including cranial nerve palsy (CNP), parkinsonism, and Guillain-Barré syndrome, along with clinical outcomes and treatment responses.

Non-ICANS neurologic events were infrequent in both treatment groups. Among patients with 1–3 prior LOT (n=73; median follow-up 6.1 months), 4 experienced CNP and no cases of parkinsonism or Guillain-Barré syndrome were observed. Among patients with ≥4 prior LOT (n=98; median follow-up 17.4 months), 3 experienced CNP, 1 developed parkinsonism, and 1 developed Guillain-Barré syndrome. Most patients with CNP had symptom improvement following management, and the Guillain-Barré syndrome case resolved. All patients with available response assessments achieved at least a partial response to cilta-cel, and no deaths were reported during follow-up. Patients with non-ICANS neurologic events had numerically higher peak post-infusion ALC values than those without events.

Key points 
• Total cohort: 171 patients with RRMM treated with cilta-cel 
• Stratification by prior therapy: 
 - 1–3 prior LOT (n=73) 
 - ≥4 prior LOT (n=98)

• Non-ICANS neurologic events assessed: 
 - Cranial nerve palsy (CNP) 
 - Parkinsonism 
 - Guillain-Barré syndrome

• Event incidence: 
 - 1–3 LOT: CNP in 4 patients; no parkinsonism or Guillain-Barré syndrome 
 - ≥4 LOT: CNP in 3 patients; parkinsonism in 1; Guillain-Barré syndrome in 1

• Clinical outcomes: 
 - Most CNP cases improved after management 
 - Guillain-Barré syndrome resolved in the reported case

• All patients with available response assessments achieved at least partial response to cilta-cel 
• No deaths reported during follow-up 
• Patients with neurologic events had numerically higher peak post-infusion ALC values than those without events

Strengths 
• Real-world electronic medical record–based dataset from Loopback Analytics supplemented with physician notes 
• Inclusion of patients treated across two defined prior therapy strata (1–3 LOT and ≥4 LOT) 
• Focus on clinically characterized non-ICANS neurologic events following CAR-T therapy

Limitations 
• Retrospective EMR-based design with potential for incomplete event capture 
• Possible misclassification due to coding and documentation variability 
• Small number of neurologic events limiting statistical precision and generalizability 
• Incomplete availability of daily ALC measurements, affecting peak ALC estimation 
• Potential selection bias due to exclusion of patients without ALC data or with baseline neurologic events

Why this study matters 
In this real-world cohort of patients with RRMM treated with cilta-cel, non-ICANS neurologic events (CNP, parkinsonism, and Guillain-Barré syndrome) were infrequent across both prior-line treatment strata. Most cranial nerve palsy cases improved with management, and the single case of Guillain-Barré syndrome resolved. All patients with available response assessments achieved at least a partial response to cilta-cel, and no deaths were reported during follow-up. Patients with non-ICANS neurologic events showed numerically higher post-infusion ALC values than those without events; however, the clinical significance of this observation remains undetermined within this study and warrants further investigation.

Reference: 
Hansen, D. K., Castaneda Puglianini, O. A., Grajales-Cruz, A., Nagar, S. P., Ghosh, S., Alegria, V., … Janakiram, M. (2026). Real-World Incidence and Management of Non-Immune Effector Cell-Associated Neurotoxicity Syndrome Neurologic Events Following Ciltacabtagene Autoleucel in Multiple Myeloma. Clinical Epidemiology, 18. https://doi.org/10.2147/CLEP.S615866 (https://www.tandfonline.com/doi/full/10.2147/CLEP.S615866)

 
Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), with or without Daratumumab in Relapsed Multiple Myeloma — Clinical Lymphoma Myeloma and Leukemia (May 2026)

What is the purpose of the study? 
This open-label, multi-arm phase 2 study evaluated the safety, tolerability, and efficacy of weekly oral ixazomib-based combinations in patients with relapsed multiple myeloma (MM). The study specifically assessed ixazomib with cyclophosphamide and dexamethasone (ICd), with or without the addition of daratumumab (Dara-ICd).

Summary 
A total of 57 patients were enrolled (33 in ICd and 24 in Dara-ICd). The overall response rate (ORR) was 73% for ICd and 75% for Dara-ICd, with ≥very good partial response (≥VGPR) rates of 45% and 54%, respectively. Median progression-free survival (PFS) was 27.1 months (95% CI: 17.8–38.6) for ICd and 37.7 months (95% CI: 17.9–not estimable) for Dara-ICd, while median overall survival was not reached in either arm.

Key points
• Design: Open-label, multi-arm phase 2 trial in relapsed multiple myeloma 
• Interventions: Ixazomib + cyclophosphamide + dexamethasone (ICd) ± daratumumab 
• Efficacy: ORR 73% (ICd) vs 75% (Dara-ICd); ≥VGPR 45% vs 54% 
• Progression-free survival: 27.1 vs 37.7 months, favoring Dara-ICd 
• Overall survival: Not reached in either treatment arm 
• Safety: Grade ≥3 treatment-related hematologic adverse events occurred in ~75% of patients 
• Strengths: Multi-arm evaluation, clinically meaningful follow-up duration, assessment of all-oral backbone regimen feasibility 
• Limitations: Small sample size, non-randomized design, open-label nature, and reliance on indirect comparisons between arms

Why this study matters 
Ixazomib-based combinations (ICd ± daratumumab) demonstrated clinically meaningful activity in relapsed multiple myeloma, with high response rates and durable progression-free survival. The addition of daratumumab was associated with deeper responses and longer PFS in indirect comparison. However, the non-randomized phase 2 design and small cohort size limit definitive comparative conclusions between treatment arms.

Reference: 
Shaji K. Kumar, Betsy Knopf, Erik Asmus, Morie Gertz, Prashant Kapoor, Suzanne Hayman, Vivek Roy, Amie Fonder, Lisa Christenson, Miriam Hobbs, Leif Bergsagel, Rafael Fonseca, David Dingli, Angela Dispenzieri, Wilson Gonsalves, Taxiarchis Kourelis, Taimur Sher, Mustaqeem Siddiqi, Rahma Warsame, Sikander Ailawadhi, S. Vincent Rajkumar, Francis Buadi, Ixazomib, Cyclophosphamide, and Dexamethasone (ICd), with or without Daratumumab in Relapsed Multiple Myeloma, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.05.004. (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(26)00149-7/abstract)

Clinical-grade armored BCMA CAR T cells overcome TGF-β–mediated immunosuppression in multiple myeloma — Blood Immunology & Cellular Therapy (June 2026)

What is the purpose of the study? 
To engineer BCMA-targeted CAR T cells that resist transforming growth factor β (TGF-β)–mediated immunosuppression in the multiple myeloma (MM) bone marrow microenvironment. The approach involves coexpressing a dominant-negative TGF-β receptor II (DNTGF-βRII) to improve CAR T-cell function under suppressive conditions.

Summary 
The investigators developed “armored” BCMA CAR T cells expressing DNTGF-βRII and manufactured them using IL-7/IL-15 conditions on the CliniMACS Prodigy platform, achieving products that met clinical release criteria. In vitro, these cells showed reduced pSmad2/3 signaling and reduced T-cell exhaustion when exposed to TGF-β1, along with maintained cytotoxicity against primary MM cells. In xenograft mouse models, armored CAR T cells reduced or eliminated tumor burden and persisted in vivo, and treated NSG mice showed no tumor after rechallenge with MM cells.

Key points 
• BCMA CAR T-cell therapy is effective in multiple myeloma but relapse is associated with TGF-β–driven immunosuppression in the bone marrow microenvironment. 
• Armored BCMA CAR T cells were engineered to coexpress a dominant-negative TGF-β receptor II to interfere with TGF-β signaling. 
• Manufacturing using IL-7/IL-15 on the CliniMACS Prodigy platform produced CAR T-cell products that met clinical release criteria. 
• In vitro exposure to TGF-β1 resulted in reduced pSmad2/3 signaling and reduced markers of T-cell exhaustion in armored CAR T cells compared with controls. 
• Armored CAR T cells demonstrated cytotoxic activity against primary multiple myeloma tumor cells, including cells with prior BCMA exposure. 
• In xenograft mouse models, treatment led to tumor burden reduction or elimination and CAR T-cell persistence. 
• In NSG mouse rechallenge experiments, no tumor was observed following reintroduction of MM cells.

Strengths
• Clinically compatible manufacturing process
• Mechanistic assessment of TGF-β signaling resistance
• Evaluation across in vitro and in vivo preclinical models

Limitations
• Findings are restricted to preclinical models
• Tumor microenvironment in multiple myeloma may involve additional immunosuppressive mechanisms not addressed in this study
• Clinical efficacy and safety remain untested

Why this study matters 
The study demonstrates that BCMA CAR T cells engineered with a dominant-negative TGF-β receptor II can reduce TGF-β signaling and maintain antitumor activity in preclinical multiple myeloma models. These cells showed functional activity in vitro and tumor control with persistence in mouse xenograft systems. Clinical evaluation will be required to determine whether these effects translate into safety and efficacy in patients.

Reference: 
Deepak Parashar, Katie Palen, Ansul Sharma, Swadha Pandey, Tyce Kearl, Peirong Hu, Peiman Hematti, Sabari Venniyil Radhakrishnan, Fumou Sun, Siegfried Janz, Bryon Johnson, Dina Schneider, Nirav Shah, Binod Dhakal; Clinical-grade armored BCMA CAR T cells overcome TGF-β–mediated immunosuppression in multiple myeloma. Blood Immunology & Cellular Therapy 2026; 2 (2): 100048. doi: https://doi.org/10.1016/j.bict.2026.100048 (https://www.sciencedirect.com/science/article/pii/S3050597626000187?via%3Dihub)

Chimeric antigen receptor T-cell therapy is equally effective and safe in older (≥70) and younger patients with multiple myeloma: a multicenter retrospective analysis — Blood Cancer Journal (June 2026)

What is the purpose of the study? 
To evaluate whether age ≥70 years influences the efficacy and safety of BCMA-directed chimeric antigen receptor T-cell (CAR-T) therapies—idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel)—in patients with relapsed/refractory multiple myeloma (r/r MM). The aim is to compare clinical outcomes and treatment-related toxicities between older and younger patients treated in routine clinical practice.

Summary 
In this retrospective multicenter study, a total of 148 patients with r/r MM treated with BCMA-directed CAR-T therapy at seven German and one Swiss centers between March 2022 and September 2024 were included, comprising 52 patients aged ≥70 years and 96 patients aged <70 years. Older patients had substantially higher rates of comorbidity and frailty but similar disease characteristics, prior treatment exposure, and disease status at CAR-T infusion compared with younger patients. At 12 months, no statistically significant differences were observed between age groups in relapse incidence, progression-free survival (PFS), or overall survival (OS). The proportion of patients achieving a complete response (CR) or at least a partial response ((VG)PR) was higher in the older cohort (94.1% vs. 78.7%; p=0.002).

Treatment-related toxicities, including severe cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic recovery, and immunoglobulin recovery, were generally similar between age groups. Although non-relapse mortality (NRM) was numerically higher in older patients (17.1% vs. 6.7%), this difference was not statistically significant (p=0.10). Multivariable analyses indicated that disease biology, as reflected by high-risk MyCARe scores, frailty, and prior treatment burden were more strongly associated with outcomes than chronological age alone.

Key points

Study population 
• 148 patients with relapsed/refractory multiple myeloma received BCMA-directed CAR-T therapy: 
 - ide-cel: 140 patients 
 - cilta-cel: 8 patients

• Age groups: 
 - <70 years: 96 patients (64.9%) 
 - ≥70 years: 52 patients (35.1%)

• Older patients had: 
 - Higher comorbidity burden (CCI ≥4: 71.2% vs. 28.1%; p<0.001) 
 - Higher frailty rates (84.0% vs. 55.6%)

Efficacy outcomes 
• 12-month relapse incidence: 
 - ≥70 years: 41.4% (95% CI 22.3–59.5%) 
 - <70 years: 48.3% (95% CI 35.6–59.9%)

• 12-month progression-free survival (PFS): 
 - ≥70 years: 47.8% 
 - <70 years: 43.5%

• 12-month overall survival (OS): 
 - ≥70 years: 68.4% 
 - <70 years: 74.4%

• No statistically significant differences were observed between age groups for relapse incidence, PFS, or OS.

• Patients achieving CR or at least a partial response ((VG)PR): 
 - ≥70 years: 94.1% 
 - <70 years: 78.7% 
 - p=0.002

• Complete response (CR) rates: 
 - ≥70 years: 58.8% 
 - <70 years: 42.6%

• The higher response rates observed in older patients should be interpreted cautiously because patient-selection factors may have influenced outcomes in this retrospective study.

Safety outcomes 
• Severe CRS (grade >2): 
 - ≥70 years: 7.7% 
 - <70 years: 7.4%

• Grade >2 ICANS: 
 - ≥70 years: 0% 
 - <70 years: 3.2%

• Hematologic recovery and immunoglobulin nadirs were comparable between groups. 
• Non-relapse mortality (NRM): 
 - ≥70 years: 17.1% 
 - <70 years: 6.7% 
 - Difference not statistically significant (p=0.10)

• The authors report that non-relapse mortality was predominantly infection-related, emphasizing the importance of infection monitoring, prophylaxis, vaccination strategies, and immunoglobulin replacement when clinically indicated.

Factors associated with outcomes 
• High-risk MyCARe score was independently associated with: 
 - Increased relapse risk 
 - Inferior PFS 
 - Inferior OS

• Frailty was associated with worse OS
• A greater number of prior therapy lines was associated with shorter PFS
• Prior HDCT/ASCT was associated with lower NRM risk and improved survival outcomes
• Age group was not significantly associated with relapse incidence, PFS, OS, or NRM after multivariable adjustment

Strengths 
• Multicenter real-world study conducted across eight institutions
• Included a substantial proportion of older adults, who are often underrepresented in CAR-T clinical trials
• Most elderly patients were frail (84%), increasing the relevance of the findings to routine clinical practice
• Propensity score matching produced findings consistent with the primary analyses, although residual confounding cannot be excluded because of the retrospective study design.

Limitations 
• Retrospective observational design
• Relatively small sample size, particularly in the ≥70-year subgroup
• Short median follow-up (8.7 months), limiting evaluation of long-term outcomes and durability of response
• Potential selection bias, as older patients may have undergone more stringent eligibility assessment before CAR-T treatment
• Predominance of ide-cel recipients limits conclusions regarding cilta-cel
• Limited statistical power to detect differences in uncommon outcomes such as non-relapse mortality.

Why this study matters 
In this real-world multicenter study, no statistically significant differences were observed between patients aged ≥70 years and younger patients in relapse incidence, progression-free survival, overall survival, or measured treatment-related toxicities following BCMA-directed CAR-T therapy for relapsed/refractory multiple myeloma. Although non-relapse mortality was numerically higher among older patients and was reported to be predominantly infection-related, age group was not significantly associated with adverse outcomes after multivariable adjustment. Disease biology, particularly high-risk MyCARe status, frailty, and treatment history appeared to have greater prognostic importance than chronological age, supporting individualized assessment when considering CAR-T therapy in older adults.

Reference: 
Berning, P., Maulhardt, M., Boyadzhiev, H. et al. Chimeric antigen receptor T-cell therapy is equally effective and safe in older (≥70) and younger patients with multiple myeloma: a multicenter retrospective analysis. Blood Cancer J. 16, 88 (2026). https://doi.org/10.1038/s41408-026-01531-w (https://link.springer.com/article/10.1038/s41408-026-01531-w)

Simulation Framework to Investigate Efficacy and Ocular Safety of Belantamab Mafodotin Combinations in Relapsed/Refractory Multiple Myeloma — CPT: Pharmacometrics & Systems Pharmacology (June 2026)

What is the purpose of the study? 
To develop and assess an integrated quantitative simulation framework for belantamab mafodotin in relapsed/refractory multiple myeloma (RRMM) that could predict treatment efficacy, safety, and the effects of dose modifications across monotherapy and combination regimens. The framework was intended to support evaluation of alternative dosing strategies and benefit–risk profiles.

Summary 
Researchers integrated pharmacokinetic, efficacy, and safety models using data from belantamab mafodotin monotherapy studies and combination studies with bortezomib/dexamethasone (BVd) and pomalidomide/dexamethasone (BPd). Changes in serum M-protein concentrations were modeled using a tumor growth inhibition model, while ophthalmic exam findings (OEFs) graded by the Keratopathy and Visual Acuity (KVA) scale were modeled using a continuous-time Markov model.

The integrated framework produced efficacy and safety outcomes that generally aligned with those observed in phase 3 DREAMM-7 and DREAMM-8 trials. Comparisons of simulated and observed data included very good partial response or better (VGPR+) rates, median progression-free survival (mPFS), and grade ≥3 ophthalmic exam findings (OEFs). Simulations of alternative dosing strategies suggested that a 2.5 mg/kg starting dose was associated with the highest predicted efficacy among the regimens evaluated, and that extending dosing intervals after the initial dose could reduce ocular toxicity without substantially affecting predicted efficacy.

Key points

Most important findings 
• An integrated modeling framework combined: 
 - Population pharmacokinetics of belantamab mafodotin. 
 - Serum M-protein response modeling. 
 - KVA-grade ophthalmic toxicity modeling.

• Simulations generated by the framework produced results that generally aligned with those observed in: 
 - DREAMM-7 (BVd): VGPR+ rate: 62.0% simulated vs 62.0% observed; mPFS: 39.4 vs 36.6 months; Grade ≥3 OEFs: 87.5% vs 76.5%. 
 - DREAMM-8 (BPd): VGPR+ rate: 60.2% vs 68.0%; mPFS: not reached in both simulated and observed data;Grade ≥3 OEFs: 77.2% vs 82.5%.

• The model predicted that higher belantamab mafodotin concentrations were associated with increased probabilities of upward transitions in KVA grades. 
• Alternative dosing schedules with planned interval extensions were predicted to reduce ocular toxicity without substantially affecting predicted efficacy. 
• Lower starting doses (e.g., 1.9 mg/kg every 8 weeks in BVd) were predicted to have lower efficacy than the regimens used in DREAMM-7.

Strengths 
• Included data from multiple belantamab mafodotin monotherapy and combination therapy studies across different treatment lines. 
• Integrated efficacy, safety, and pharmacokinetic data into a single simulation framework. 
• Used a continuous-time Markov model, allowing flexibility in modeling dose modifications and observation schedules. 
• Simulation results generally aligned with efficacy and safety outcomes observed in two phase 3 trials.

Limitations 
• Included only patients with response assessments based on serum M-protein measurements. 
• The ophthalmic toxicity model was stochastic and may not fully capture more complex transitions between KVA grades. 
• Simulations were based on protocol-specified dosing and may not reflect all treatment modifications that occurred in clinical practice or trials. 
• The framework assumed that any direct statistical relationship between efficacy and ocular toxicity was non-influential. 
• Predictions outside the range of observed clinical data (e.g., substantially different exposures or dosing schedules) should be interpreted cautiously and require further clinical validation.

Why this study matters 
This study developed an integrated pharmacokinetic, efficacy, and ocular safety simulation framework for belantamab mafodotin in relapsed/refractory multiple myeloma. The framework produced efficacy and safety outcomes that generally aligned with those observed in the DREAMM-7 and DREAMM-8 trials and was used to evaluate alternative dosing strategies. Simulations suggested that the dosing regimens used in DREAMM-7 and DREAMM-8 were associated with the highest predicted efficacy among the regimens evaluated and that schedule extensions after the initial dosing periods could reduce ocular toxicity without substantially affecting predicted efficacy, although further clinical validation is required.

Reference: 
F. Carreño, M. van Noort, A. Taylor, et al., “Simulation Framework to Investigate Efficacy and Ocular Safety of Belantamab Mafodotin Combinations in Relapsed/Refractory Multiple Myeloma,” CPT: Pharmacometrics & Systems Pharmacology 15, no. 6 (2026): e70276, https://doi.org/10.1002/psp4.70276. (https://ascpt.onlinelibrary.wiley.com/doi/10.1002/psp4.70276)

 
D-VRD induction and autologous transplant in patients ≥70 years — Blood Cancer Journal (June 2026)

What is the purpose of the study? 
To evaluate outcomes of daratumumab, bortezomib, lenalidomide, and dexamethasone (D-VRD) induction followed by autologous hematopoietic cell transplantation (autoHCT) in newly diagnosed multiple myeloma patients aged ≥70 years compared with those <70 years. The aim is to assess progression-free survival (PFS), overall survival (OS), response depth, and safety in older transplant-eligible patients.

Summary  
A total of 125 newly diagnosed multiple myeloma patients treated at a single center (2021–2024) received D-VRD induction followed by autoHCT, including 27 patients aged ≥70 years and 98 patients aged <70 years. After inverse probability weighting adjustment, no statistically significant differences were observed between age groups in PFS (HR 1.30, 95% CI 0.36–4.67; p=0.69) or OS (HR 0.49, 95% CI 0.02–14.29; p=0.68), and no non-relapse mortality events occurred in either cohort. Post-transplant response rates were ≥VGPR in 26/27 (96%) patients aged ≥70 years and 92/98 (94%) patients aged <70 years, with ≥CR in 17/27 (63%) and 48/98 (49%), respectively.

Key points 
• Design: Single-center retrospective cohort study (MD Anderson Cancer Center) of 125 newly diagnosed multiple myeloma patients treated with D-VRD induction followed by upfront autoHCT (2021–2024). 
• Population: 27 patients aged ≥70 years (median 74 years, range 70–78) and 98 patients aged <70 years (median 59 years, range 40–69). 
• Adjustment: Stabilized inverse probability weighting used to adjust for baseline differences including R-ISS stage, HCT-CI, cytogenetics, conditioning regimen, and maintenance therapy. 
• Pre-transplant response: ≥VGPR in 22/27 (81%) vs 76/98 (78%); ≥CR in 8/27 (30%) vs 24/98 (24%) for ≥70 vs <70 years, respectively. 
• Post-transplant response: ≥VGPR: 26/27 (96%) vs 92/98 (94%); ≥CR: 17/27 (63%) vs 48/98 (49%) 
• MRD (post-transplant, evaluable patients only): 6/12 (50%) vs 45/60 (75%) achieved MRD negativity in ≥70 vs <70 years, respectively. 
• Survival outcomes: 
 - Median follow-up: 15.0 months (≥70) vs 19.9 months (<70); overall median 19.1 months (range 3.6–47.4). 
 - Median PFS: 36.5 months (≥70) vs not reached (<70). 
 - One- and two-year PFS: 91% and 78% (≥70) vs 93% and 89% (<70). 
 - One- and two-year OS: 100% and 92% (≥70) vs 98% and 93% (<70). 
 - No statistically significant differences in adjusted PFS or OS.

• Safety: No non-relapse mortality in either group. Median neutrophil engraftment was 12 days in both cohorts; median platelet engraftment was 14 days (≥70) vs 13 days (<70). Four second primary malignancies occurred, all in the <70 cohort.

Strengths 
• Inclusion of real-world patients aged up to 78 years receiving contemporary D-VRD induction followed by autoHCT. 
• Use of inverse probability weighting to adjust for measured baseline differences. 
• Standardized reporting of response, MRD (where available), engraftment, and survival endpoints.

Limitations 
• Retrospective, single-center design with potential for selection bias. 
• Small sample size in the ≥70-year cohort (n=27), limiting precision of effect estimates. 
• Short and unequal follow-up between groups. 
• Missing MRD data in a subset of patients (12/27 vs 60/98 post-transplant evaluable). 
• Lack of standardized frailty assessment and heterogeneity in induction and conditioning regimens. 
• Absence of a non-transplant comparator arm precludes assessment of relative benefit of autoHCT.

Why this study matters 
In this selected cohort of transplant-eligible patients with newly diagnosed multiple myeloma, D-VRD induction followed by autoHCT was associated with high rates of deep response and no statistically significant differences in adjusted PFS or OS between patients aged ≥70 and <70 years. MRD negativity rates post-transplant were lower in the ≥70-year group among evaluable patients, though based on incomplete data. Interpretation is limited by retrospective design, small sample size in older patients, and incomplete follow-up and MRD assessment.

Reference: 
Pasvolsky, O., Marcoux, C., Milton, D.R. et al. D-VRD induction and autologous transplant in patients ≥70 years. Blood Cancer J. 16, 91 (2026). https://doi.org/10.1038/s41408-026-01522-x (https://link.springer.com/article/10.1038/s41408-026-01522-x)

 
Real-world application of the International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) consensus on genomic staging for high-risk multiple myeloma: A report from the Australia and New Zealand Myeloma and Related Diseases Registry — British Journal of Haematology (June 2026)

What is the purpose of the study? 
To evaluate the performance of the newly proposed International Myeloma Society/International Myeloma Working Group (IMS/IMWG) Consensus Genomic Staging high-risk criteria (CGS-HR) in a real-world cohort of patients with newly diagnosed multiple myeloma (NDMM). The researchers aim to determine whether the criteria predict survival outcomes and early disease progression, including in patient groups often underrepresented in clinical trials, such as frail individuals and those with renal impairment.

Summary 
Using data from the Australia and New Zealand Myeloma and Related Diseases Registry, investigators analyzed 567 patients with determinable modified IMS/IMWG CGS risk status. Of these, 166 patients were classified as high-risk (mod-IMS/IMWG CGS-HR). Patients with high-risk disease had significantly shorter overall survival (median 45.7 vs 85.5 months) and progression-free survival on first-line therapy (median 23.0 vs 38.9 months) compared with standard-risk patients, with nearly double the risk of death (hazard ratio [HR] 1.90, 95% CI 1.41–2.55).

The prognostic value of mod-IMS/IMWG CGS-HR was strongest in transplant-eligible, non-frail patients and those with preserved renal function. High-risk status was associated with 2.2-fold increased odds of early progression within 18 months of starting first-line therapy, but it did not outperform established staging systems (ISS, R-ISS, or R2-ISS) for identifying functional high-risk disease characterized by early relapse.

Key points

Main findings 
• 567 patients had sufficient data for risk classification; 166 were classified as mod-IMS/IMWG CGS-HR. 
• Among patients with complete data, approximately 22% were classified as high-risk. 
• High-risk patients had: 
 - Median overall survival (OS): 45.7 months vs 85.5 months for standard-risk patients. 
 - Median first-line progression-free survival (PFS-1): 23.0 months vs 38.9 months. 
 - Nearly 2-fold higher risk of death (HR 1.90; 95% CI 1.41–2.55; p<0.001).

• Patients meeting more than one high-risk criterion had particularly poor outcomes (median OS 37.0 months; median PFS 15.6 months). 
• High-risk status was associated with 2.2-fold higher odds of early progression (PFS-1 <18 months).

Subgroup findings 
• Prognostic discrimination was strongest in: 
 - Transplant-eligible patients (HR for death 2.73). 
 - Non-frail patients (HR 3.22). 
 - Patients with normal renal function (HR 2.33).

• Associations were not statistically significant in: 
 - Transplant-ineligible patients. 
 - Frail patients
 - Patients with renal impairment

Strengths 
• Large real-world cohort from 21 centers across Australia and New Zealand. 
• External validation of the IMS/IMWG CGS-HR criteria outside clinical trial populations. 
• Comprehensive cytogenetic and fluorescence in situ hybridization (FISH) data. 
• Inclusion of patient groups often underrepresented in clinical trials.

Limitations 
• Retrospective study design with missing data; 265 patients could not be classified. 
• TP53 mutation testing was not routinely available and was not included in risk assessment. 
• Biallelic del(1p32) was assessed by FISH rather than recommended next-generation sequencing (NGS), potentially underestimating some high-risk cases. 
• Limited comorbidity information may have affected frailty classification. 
• No patients received contemporary frontline quadruplet regimens, which may limit applicability to current treatment practice.

Why this study matters 
In this real-world multiple myeloma cohort, the modified IMS/IMWG CGS-HR criteria identified approximately one-quarter of patients as high-risk and were associated with significantly shorter survival and higher risk of early disease progression. The criteria showed the strongest prognostic value in transplant-eligible, non-frail patients and those with preserved renal function, but their performance was less clear in frail, transplant-ineligible, and renally impaired populations. Although CGS-HR captures biologically high-risk disease, it did not outperform existing staging systems for identifying patients at risk of early relapse, indicating that treatment response assessment remains an important component of risk evaluation.

Reference: 
Lim, K.J.C., Ashrafi, E., Wellard, C., Moore, E.M., Gration, B., Augustson, B., Mollee, P., Zhang, J., Doo, N.W., Dun, K., Cooke, R., Ringkowski, S., Bryant, A., McCaughan, G., Wood, E., McQuilten, Z., Ho, P.J., Quach, H. and Spencer, A. (2026), Real-world application of the International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) consensus on genomic staging for high-risk multiple myeloma: A report from the Australia and New Zealand Myeloma and Related Diseases Registry. Br J Haematol. https://doi.org/10.1111/bjh.70609 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70609)

Sustained disease remission after a limited duration of bispecific antibody therapy in patients with multiple myeloma — HemaSphere (June 2026)

What is the purpose of the study? 
To evaluate outcomes in patients with relapsed/refractory multiple myeloma (RRMM) who discontinued bispecific antibody (bsAb) therapy after achieving remission and remained off treatment for at least 3 months. The study assesses the durability of remission, relapse risk, immune recovery, and infection burden following finite duration bsAb therapy.

Summary 
Among 860 patients treated with bsAbs across seven institutions, 81 patients who discontinued therapy for reasons other than disease progression and maintained remission for at least 3 months were analyzed. The median duration of bsAb therapy was 7 months, and 76% of patients had achieved complete remission (CR) at treatment discontinuation. After a median follow-up of 19 months off therapy, the 36-month relapse-free survival (RFS) was 62% (95% CI, 48%–80%), with an estimated median RFS of 43 months; seven patients remained in remission for at least 3 years after stopping treatment.

The presence of extramedullary disease (EMD) (HR 7.42; 95% CI 2.29–24) and receipt of ≥6 prior lines of therapy (HR 8.17; 95% CI 2.02–33) were associated with shorter RFS. Severe infections (≥Grade 3) remained common after treatment discontinuation, with a 36-month cumulative incidence of 41%, but infection rates decreased over time. Serum IgG levels increased by approximately 14 mg/dL per month after stopping treatment, and nearly 90% of patients achieved normal IgG levels by approximately 900 days after treatment cessation.

Key points

Patient population 
• 81 patients with RRMM treated with BCMA- and/or GPRC5D-targeting bsAbs
• Median age: 70 years (range 26–86)
• Median prior lines of therapy: 4 (range 1–9)
• High-risk cytogenetics present in 48% of patients
• Extramedullary disease (EMD) present in 7.7%

Treatment and response 
• Median bsAb treatment duration: 7 months (range 1–40)
• 32% received treatment for more than 1 year before discontinuation
• 76% achieved CR at treatment discontinuation 
• Most common reasons for discontinuation: 
 - Infections: 48% 
 - Skin and nail adverse effects: 12%

Efficacy outcomes 
• Median follow-up after discontinuation: 19 months. 
• 36-month RFS: 62% (95% CI, 48%–80%). 
• Estimated median RFS: 43 months. 
• 7 patients maintained remission for at least 3 years after stopping therapy
• 36-month relapse mortality: 30%
• 36-month non-relapse mortality: 7.7%

Factors associated with inferior RFS 
• Presence of EMD: 
 - HR 7.42 (95% CI 2.29–24; P≤0.001). 
 - 36-month RFS: 17%. 
 - Median RFS: 10 months.

• ≥6 prior lines of therapy: 
 - HR 8.17 (95% CI 2.02–33; P≤0.003). 
 - 36-month RFS: 41%. 
 - Median RFS: 29 months.

Infection and immune recovery 
• 74 ≥Grade 3 infection events occurred in 28 patients. 
• Three Grade 5 infections were reported. 
• 36-month cumulative incidence of first ≥Grade 3 infection: 41%. 
• Infection rates decreased after approximately 6 months off therapy and reached zero beyond 900 days. 
• 67.4% of patients remained hypogammaglobulinemic at 180 days after discontinuation. 
• IgG levels increased by approximately 14 mg/dL per month after stopping treatment. 
• Nearly 90% achieved normalized IgG levels by approximately 900 days. 
• Use of intravenous immunoglobulin (IVIG) decreased over time.

Strengths 
• Multicenter cohort from seven institutions. 
• Extended follow-up after treatment discontinuation (up to 61 months). 
• Evaluation of both disease control and immune reconstitution outcomes. 
• Included real-world and clinical trial patients.

Limitations 
• Retrospective study design. 
• Heterogeneous patient population and treatment regimens. 
• Inclusion required at least 3 months of remission after discontinuation, which may have introduced selection bias. 
• Lack of a continuous treatment control group. 
• Findings may be less generalizable to patients who do not achieve deep remission before discontinuation.

Why this study matters 
In this retrospective multicenter cohort of 81 patients with RRMM who discontinued bispecific antibody therapy while in remission, the 36-month relapse-free survival was 62% (95% CI, 48%–80%), with an estimated median relapse-free survival of 43 months. The presence of extramedullary disease and receipt of ≥6 prior lines of therapy were associated with shorter relapse-free survival. After treatment discontinuation, serum IgG levels increased over time, IVIG use decreased, and rates of ≥Grade 3 infections declined, although severe infections continued to occur during follow-up.

Reference: 
Vega, G., Morillo, D., Riedhammer, C., Smits, F., Bag, A., Julian, K., Gomis, N.T., Gaisan, C.M., Bermudez, M.A., Shah, M.R., Mohyuddin, G.R., Dhakal, B., Rasche, L., Schinke, C., D'Souza, A., Szabo, A., van de Donk, N.W.C.J., Chakraborty, R. and Mohan, M. (2026), Sustained disease remission after a limited duration of bispecific antibody therapy in patients with multiple myeloma. HemaSphere, 10: e70396. https://doi.org/10.1002/hem3.70396 (https://onlinelibrary.wiley.com/doi/10.1002/hem3.70396)

Addressing Diagnostics Delay in Multiple Myeloma: Insights from a National Survey of Primary Care Providers — The Journal of Applied Laboratory Medicine (June 2026)

What is the purpose of the study? 
To evaluate the knowledge, awareness, and confidence of U.S. primary care providers (PCPs) in identifying and diagnosing multiple myeloma (MM) and related plasma cell disorders. It also examines adherence to recommended diagnostic testing practices and barriers to appropriate evaluation.

Summary 
A survey conducted between October and December 2024 included 560 PCPs representative of the U.S. primary care workforce. Of these, 300 PCPs who had ordered serum protein electrophoresis (SPEP) within the previous 12 months and believed SPEP should be ordered for plasma cell disorder diagnosis completed additional survey questions.

Among the representative cohort, 46% either had not ordered SPEP in the previous 12 months or did not believe SPEP should be ordered for plasma cell disorder diagnosis. Among the 300 PCPs who evaluated plasma cell disorders and completed the detailed survey, responses indicated generally good awareness of MM symptoms and risk factors, but only 28% reported using guideline-recommended paired testing with SPEP and serum free light chains (sFLC). Most respondents (80%) reported low confidence in selecting and interpreting diagnostic tests and frequently relied on colleagues or hematologists for guidance. Access to myeloma-specific diagnostic ordering sets and panels was limited, with 15% reporting use of such resources and 54% expressing interest in using them.

Key points 
• Study design: Cross-sectional survey conducted from October to December 2024. 
• Participants: 560 PCPs met criteria for a representative U.S. PCP cohort; 300 PCPs who had ordered SPEP in the previous 12 months and considered it appropriate for plasma cell disorder diagnosis completed additional survey questions.

• Testing practices: 
 - 46% of the representative PCP cohort either had not ordered SPEP in the previous 12 months or did not believe SPEP should be ordered for plasma cell disorder diagnosis. 
 - Among the 300 PCPs who completed the detailed survey, 28% reported using guideline-recommended paired SPEP and sFLC testing.

• Knowledge and confidence: 
 - Survey responses indicated generally good awareness of MM symptoms and risk factors among PCPs who evaluated plasma cell disorders. 
 - 80% reported low confidence in selecting and interpreting diagnostic tests. 
 - Many respondents reported relying on peers and hematologists for assistance with test selection and interpretation.

• Diagnostic support tools: 
 - 15% reported access to and use of myeloma diagnostic ordering sets or panels. 
 - 54% expressed interest in using such tools.

• Reported barriers: 
 - Insufficient education regarding MM diagnosis. 
 - Limited collaboration and specialist support. 
 - Challenges selecting and interpreting diagnostic tests. 
 - Lack of clear diagnostic protocols and support resources.

• Related evidence cited by the authors: The authors note that prior studies have shown that SPEP without sFLC testing may miss approximately 1 in 8 patients with MM, particularly those with light-chain-only or non-secretory disease.

Methodological strengths 
• Included a large cohort of PCPs designed to be representative of the U.S. primary care workforce. 
• Collected both quantitative and qualitative survey data. 
• Evaluated knowledge, testing practices, confidence, and perceived barriers related to MM diagnosis.

Limitations 
• The study could not assess awareness and practices among the 46% of representative PCPs who either had not ordered SPEP in the previous 12 months or did not believe SPEP should be ordered for plasma cell disorder diagnosis. 
• Survey wording and terminology may have been interpreted differently across respondents, potentially contributing to variability in responses. 
• Findings were based on self-reported survey responses rather than direct observation of clinical practice.

Why this study matters 
This survey identified gaps in knowledge, confidence, and adherence to MM diagnostic testing guidelines among U.S. PCPs. Although survey responses indicated generally good awareness of MM symptoms and risk factors, only 28% of surveyed PCPs who evaluated plasma cell disorders reported using guideline-recommended paired SPEP and sFLC testing, and most reported low confidence in test selection and interpretation. The findings suggest gaps in MM diagnostic testing knowledge, confidence, and guideline adherence, as well as limited availability and use of diagnostic support tools.

Reference: 
Bhrugu Yagnik, Jill Pauli, Brittany Watson, Joseph Mikhael, Addressing Diagnostics Delay in Multiple Myeloma: Insights from a National Survey of Primary Care Providers, The Journal of Applied Laboratory Medicine, 2026;, jfag087, https://doi.org/10.1093/jalm/jfag087 (https://academic.oup.com/jalm/advance-article/doi/10.1093/jalm/jfag087/8704410?login=false)

 
CD20 by diagnostic flow cytometry helps discriminate monoclonal gammopathy of undetermined significance and multiple myeloma plasma cells — Discover Immunity (June 2026)

What is the purpose of the study? 
To evaluate the flow cytometry immunophenotype of plasma cells in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) to identify markers that may help distinguish these conditions. The study assesses whether CD20 expression differs between MGUS and MM in bone marrow plasma cell populations.

Summary 
Researchers retrospectively reviewed 267 bone marrow specimens analyzed by flow cytometry over a 12-month period at a single diagnostic laboratory in Australia. Plasma cells were assessed using antibodies against CD45, CD38, CD138, CD19, CD20, CD56, CD117, and intracellular kappa and lambda light chains, and cases were classified as normal/polyclonal plasma cells, MGUS, or MM based on medical record review.

Monoclonal plasma cells showed reduced or absent CD45 expression and loss of CD19 compared with normal plasma cells. CD20 expression was more frequently retained in MGUS cases, whereas it was typically absent in MM cases. These findings indicate differences in CD20 expression between MGUS and MM in this cohort.

Key points 
• Study design: Retrospective single-center review of bone marrow flow cytometry specimens over 12 months. 
• Population: 267 cases with plasma cell flow cytometry testing; MGUS subgroup included 23 patients. 
• Flow cytometry markers evaluated: CD45, CD38, CD138, CD19, CD20, CD56, CD117, intracellular kappa, and intracellular lambda light chains. 
• Main findings: 
 - Monoclonal plasma cells showed: Reduced or absent CD45 expression;Loss of CD19 expression. 
 - CD20 expression was more frequently present in MGUS than in MM.

• Interpretation of findings: CD20 expression differed between MGUS and MM in this cohort.

Strengths
• Relatively large real-world cohort of plasma cell cases (n=267)
• Inclusion of both MM and non-MM monoclonal plasma cell disorders, an underrepresented comparison in prior literature 
• Standardized flow cytometry approach within a routine diagnostic laboratory setting

Limitations
• Single-center study, which may limit generalizability
• Small number of MGUS cases (n=23), limiting subgroup analysis
• Retrospective design. 
• Potential need for validation in independent cohorts

Why this study matters 
In this retrospective cohort of 267 bone marrow specimens, monoclonal plasma cells showed reduced or absent CD45 expression and loss of CD19 compared with normal plasma cells. CD20 expression was more frequently observed in MGUS than in MM, indicating differences in immunophenotype between these conditions in this dataset. Further studies in larger and independent cohorts are required to confirm the reproducibility of these findings.

Reference: 
Lee, A.Y.S. CD20 by diagnostic flow cytometry helps discriminate monoclonal gammopathy of undetermined significance and multiple myeloma plasma cells. Discov. Immun. 3, 8 (2026). https://doi.org/10.1007/s44368-026-00026-x (https://link.springer.com/article/10.1007/s44368-026-00026-x)

Potential benefits and harms of screening strategies for monoclonal gammopathy of undetermined significance in the US: A simulation study — Clinical Lymphoma Myeloma and Leukemia (June 2026)

What is the purpose of the study? 
This study uses a microsimulation model of the natural history of multiple myeloma (MM) in the U.S. to evaluate the potential benefits and harms of screening for monoclonal gammopathy of undetermined significance (MGUS), an asymptomatic precursor condition to MM. The primary objective is to estimate the extent of overdiagnosis associated with different MGUS screening strategies and assess the balance between potential benefits and harms.

Summary 
Researchers developed and validated a microsimulation model that incorporated MM and MGUS risk factors, including age, sex, race, and body mass index, and evaluated 80 MGUS screening strategies that varied by screening age range and frequency. The model was validated by comparing simulated MM incidence with observed incidence data from the U.S. Surveillance, Epidemiology, and End Results (SEER) database.

Across screening strategies on the effectiveness frontier, for every additional individual whose MGUS was detected through screening and who would later develop MM, there were an estimated 3.6 to 5.9 individuals with screen-detected MGUS who would not progress to MM during their lifetime. Overall, 78% to 86% of screen-detected MGUS cases were estimated not to progress to MM. The benefits of early MGUS detection remain unknown, and any clinical benefit depends on the unproven assumption that early detection followed by surveillance improves outcomes. Unlike many cancers for which screening is recommended, MGUS is a precursor condition to an incurable hematologic malignancy, and no treatment is currently recommended for MGUS. The findings demonstrated a substantial risk of overdiagnosis across the evaluated screening strategies.

Key points 
• MGUS is an asymptomatic precursor condition that can precede MM. 
• No current recommendations support routine MGUS screening because evidence of clinical benefit remains limited. 
• The benefits of early MGUS detection remain unknown, and any clinical benefit depends on the unproven assumption that early detection followed by surveillance improves outcomes. 
• MGUS is a precursor condition to MM, an incurable hematologic malignancy, and no treatment is currently recommended for MGUS. 
• The study evaluated 80 screening strategies differing in starting age, ending age, and screening frequency. 
• A validated microsimulation model was used to estimate outcomes in the U.S. population. 
• For every additional individual whose MGUS was detected through screening and who would later develop MM, there were an estimated 3.6 to 5.9 individuals with screen-detected MGUS who would not progress to MM during their lifetime. 
• Approximately 78% to 86% of screen-detected MGUS cases were projected not to progress to MM during the individual's lifetime. 
• The authors identified several screening strategies on or near the effectiveness frontier, including screening every 10 years beginning at age 55, particularly when overdiagnosis was considered. 
• The study highlights the importance of considering overdiagnosis when evaluating MGUS screening programs. 
• The authors suggested that identifying and screening individuals at higher risk of MM may help maximize potential benefits and minimize harms.

Strengths 
• Developed and validated a natural history model using U.S. incidence data. 
• Evaluated a wide range of screening strategies with varying ages and screening intervals. 
• Incorporated multiple demographic and clinical risk factors, including age, sex, race, and body mass index. 
• Quantified the trade-off between potential screening benefits and overdiagnosis using an overdiagnosis-to-benefit ratio.

Limitations 
• The benefits of early MGUS detection remain unknown, and any clinical benefit depends on the unproven assumption that early detection followed by surveillance improves outcomes. 
• The model did not include smoldering multiple myeloma (SMM), an intermediate stage between MGUS and MM. 
• Screening tests were assumed to have 100% sensitivity and specificity, which may overestimate benefits and underestimate harms. 
• MM-specific survival outcomes and potential mortality benefits were not modeled. 
• Individual variation in MGUS development risk and progression risk was not incorporated. 
• Potential psychological effects of MGUS diagnosis were not directly evaluated.

Why this microsimulation study matters 
This microsimulation study found a substantial risk of overdiagnosis associated with MGUS screening, with most screen-detected MGUS cases not progressing to MM during a person's lifetime. Across effective screening strategies, for every additional individual whose MGUS was detected through screening and who would later develop MM, there were an estimated 3.6 to 5.9 individuals with screen-detected MGUS who would not progress to MM during their lifetime. Given the uncertainty regarding the benefits of early MGUS detection and the high proportion of screen-detected MGUS cases that were not projected to progress to MM, the authors suggested that identifying and screening individuals at higher risk may help maximize potential benefits and minimize harms.

Reference: 
Ishfaq Ahmad, Rong Wang, Natalia Neparidze, Jane Lange, Shi-Yi Wang, Potential benefits and harms of screening strategies for monoclonal gammopathy of undetermined significance in the US: A simulation study, Clinical Lymphoma Myeloma and Leukemia, 2026, ISSN 2152-2650, https://doi.org/10.1016/j.clml.2026.06.001 (https://www.clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(26)00175-8/fulltext).

Clinical Trials

Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: a US subgroup analysis from MagnetisMM-3 — Cancer (May 2026)

What is the purpose of the study? 
To evaluate the efficacy and safety of elranatamab in U.S. patients with relapsed or refractory multiple myeloma (RRMM) who had not previously received B-cell maturation antigen (BCMA)-directed therapy.

Summary 
In this post hoc analysis of the MagnetisMM-3 trial, patients received step-up dosing followed by weekly elranatamab 76 mg in 28-day cycles, with eligible responders later transitioning to dosing every 2 weeks and then every 4 weeks. Among 47 US-enrolled patients with a median follow-up of 39.6 months, the objective response rate was 66.0%, and 42.6% achieved a complete response or better. Median duration of response was 40.8 months, median progression-free survival was 27.3 months, and median overall survival was 43.6 months. Common treatment-emergent adverse events included infections, fatigue, and cytokine release syndrome, with infections representing the most frequent grade 3/4 adverse event.

Key points 
• Post hoc analysis of U.S. patients enrolled in MagnetisMM-3 
• Included 47 US patients among 123 evaluable BCMA-naive participants. 
• Patients had heavily pretreated RRMM 
• Treatment with elranatamab resulted in: 
 - Objective response rate: 66.0% (95% CI, 50.7–79.1) 
 - Complete response or better: 42.6% (95% CI, 28.3–57.8) 
 - Median duration of response: 40.8 months 
 - Median progression-free survival: 27.3 months 
 - Median overall survival: 43.6 months

• Twenty-two patients transitioned from weekly to every-2-week dosing, and eight later transitioned to every-4-week dosing.

• Among responders who transitioned dosing schedules: 
 - 77.8% maintained or improved response for at least 6 months after switching to every-2-week dosing 
 - 87.5% maintained or improved response for at least 6 months after switching to every-4-week dosing

• Common treatment-emergent adverse events: 
 - Infections: 70.2% overall; 42.6% grade 3/4 
 - Fatigue: 61.7% overall; 8.5% grade 3/4 
 - Cytokine release syndrome: 61.7%; no grade 3/4 events reported

Strengths 
• The 39.6-month median follow-up provided extended observation of response durability and survival outcomes
• Provides subgroup-specific data for US patients within a larger multicenter study
• Included assessment of response maintenance after transitions to reduced frequency dosing

Limitations 
• Post hoc subgroup analysis may limit the strength of statistical conclusions
• Small U.S. subgroup sample size (47 patients)
• Single-arm study design without a comparator group

Why this study matters 
In this post hoc analysis of U.S. patients from the MagnetisMM-3 study, Elranatamab demonstrated durable responses with reported progression-free and overall survival outcomes in heavily pretreated, BCMA-naive patients with RRMM. The safety findings were consistent with those observed in the overall MagnetisMM-3 BCMA-naive population, with infections being the most common severe adverse event. Many responders maintained or improved responses after transitioning to less frequent dosing schedules.

Reference: 
Nooka AK, Strouse C, Larson SM, et al. Efficacy and safety of elranatamab in patients with relapsed or refractory multiple myeloma: a US subgroup analysis from MagnetisMM-3. Cancer. 2026;e70442. doi:10.1002/cncr.70442 (https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.70442)

Recognising disease progression in MGUS and smouldering myeloma: Biomarkers, symptom monitoring and imaging — British Journal of Haematology (May 2026)

What is the purpose of the study? 
To analyze patients with previously diagnosed precursor conditions to multiple myeloma, including monoclonal gammopathy of undetermined significance (MGUS) and smoldering myeloma (SMM), within the Tackling Early Morbidity in Myeloma (TEAMM) trial to evaluate how symptoms, blood-based biomarkers, and imaging findings contributed to recognizing progression to active multiple myeloma (MM). It also examines challenges in identifying progression early enough to prevent complications such as fractures.

Summary 
The TEAMM trial included 977 newly diagnosed MM patients from 93 UK hospitals, of whom 133 (14%) had a known precursor condition before progressing to active MM. Patients with precursor disease reported symptoms for substantially longer before MM diagnosis than patients with de novo MM, although only 29% developed new MM-related symptoms during follow-up after their initial hematology assessment. Around 70% of patients experienced a significant increase in paraprotein levels before progression, suggesting blood-based biomarkers were more informative than symptom monitoring alone. MGUS and SMM risk scores also increased prior to progression.

Despite ongoing follow-up, fractures occurred in 25% of patients progressing from precursor disease, including some severe spinal injuries. Biomarkers and patient-reported symptoms showed limited specificity for predicting fractures, while observational comparisons discussed in the study suggest that advanced imaging techniques such as whole-body MRI and PET-CT may improve earlier detection of skeletal disease compared with conventional skeletal surveys.

Key points 
• The TEAMM trial analyzed 133 patients with prior MGUS or SMM who later developed active MM. 
• Patients with precursor disease reported symptoms for substantially longer before MM diagnosis than patients with de novo MM. 
• Only 29% developed new MM-related symptoms during follow-up after initial hematology assessment. 
• Around 70% of patients experienced a significant rise in paraprotein levels before progression. 
• MGUS and SMM risk scores generally increased before progression to active MM. 
• Fractures occurred in 25% of patients despite monitoring, highlighting challenges in early detection. 
• Biomarkers and symptoms had limited specificity for predicting fractures. 
• Observational comparisons discussed in the study suggest advanced imaging modalities, including whole-body MRI and PET-CT, may improve earlier detection of skeletal disease. 
• Limited access to advanced imaging in the UK remains a barrier to implementation of guideline-recommended monitoring.

Strengths 
• Large multicenter cohort from 93 UK hospitals. 
• Real-world assessment of progression monitoring in precursor MM conditions. 
• Combined evaluation of symptoms, biomarkers, and imaging findings.

Limitations 
• Symptom data were collected retrospectively and depended on patient recall. 
• Incomplete biomarker and imaging datasets, with only 56% having completed case report forms. 
• Some reported symptoms may have been incorrectly attributed to MM progression.

Why this study matters 
This study found that patient-reported symptoms alone were not sufficiently sensitive or specific for identifying progression from MGUS or SMM to active MM or for predicting fractures. Blood-based biomarkers, particularly rising paraprotein levels, appeared more informative for detecting progression, while observational evidence discussed in the study suggests advanced imaging methods such as whole-body MRI and PET-CT may help reduce skeletal complications through earlier detection. The findings support regular laboratory monitoring combined with functional imaging as central components of follow-up in precursor myeloma conditions.

Reference: 
Haslam A, Iqbal G, Drayson M, Pratt G, Yong K, Dunn J, Atkin C, Bunce C, Howe D, Bowcock S. Recognising disease progression in MGUS and smouldering myeloma: Biomarkers, symptom monitoring and imaging. Br J Haematol. 2026 May 20. doi: 10.1111/bjh.70492 (https://onlinelibrary.wiley.com/doi/10.1111/bjh.70492).

Anti-BCMA/GPRC5D CAR T in relapsed or refractory multiple myeloma patients with extraosseous extramedullary disease — Blood (May 2026)

What is the purpose of the study? 
To evaluate the efficacy and safety of anti-BCMA/GPRC5D bispecific CAR T-cell therapy in patients with relapsed or refractory multiple myeloma (RRMM) with extraosseous extramedullary disease (EMD), a population with historically inferior outcomes and limited treatment options. The study assesses response rates, survival outcomes, and treatment-related toxicities.

Summary 
In this single-arm, open-label phase 2 study, 37 patients with RRMM and extraosseous EMD received anti-BCMA/GPRC5D bispecific CAR T cells at a dose of 2.0 × 10⁶ CAR T cells/kg. After a median follow-up of 10.1 months, 36 of 37 patients (97%) achieved an overall response and measurable residual disease (MRD) negativity, including 16 patients (43%) who achieved stringent complete response (sCR). Median progression-free survival (PFS) was 5.8 months (95% CI: 2.2–9.4), while median overall survival (OS) was not reached at the time of analysis.

The most common grade 3 or higher adverse events were hematologic toxicities, excluding lymphopenia, which occurred in all patients. Cytokine release syndrome (CRS) occurred in 27 patients (73%), and all CRS cases were grade 1 or 2. Two patients (5%) experienced immune effector cell-associated neurotoxicity syndrome (ICANS), with grade 1 or grade 3 severity. The observed toxicities included mainly hematologic adverse events, predominantly low-grade CRS, and infrequent ICANS, and were comparable to those reported with single-target CAR T-cell therapies.

Key points 
• Anti-BCMA/GPRC5D bispecific CAR T cells produced a 97% overall response rate in RRMM patients with extraosseous EMD. 
• The study reported overall response and measurable residual disease (MRD) negativity in 36 of 37 patients. 
• Sixteen patients (43%) achieved stringent complete response (sCR). 
• Median progression-free survival (PFS) was 5.8 months (95% CI: 2.2–9.4); median overall survival (OS) was not reached at the time of analysis. 
• Grade 3 or higher hematologic toxicities were the most common adverse events. 
• Cytokine release syndrome (CRS) occurred in 73% of patients, with all cases limited to grade 1 or 2 severity. 
• Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 2 patients (5%).

Strengths 
• Evaluated RRMM patients with extraosseous EMD, who historically have inferior outcomes and limited treatment options. 
• Reported high rates of overall response, MRD negativity, and stringent complete response.

Limitations 
• Single-arm, open-label study design without a comparator group. 
• Small sample size of 37 patients. 
• Relatively short follow-up duration limited assessment of long-term survival outcomes.

Why this study matters 
Anti-BCMA/GPRC5D bispecific CAR T-cell therapy produced high overall response rates, MRD negativity, and stringent complete responses in patients with RRMM and extraosseous EMD. Median PFS was 5.8 months, and median OS was not reached at the time of analysis. The observed toxicities included mainly hematologic adverse events, predominantly low-grade CRS, and infrequent ICANS.

Reference: 
Dian Zhou, Yuekun Qi, Sha Ma, Qian Sun, Weiying Gu, Jieyun Xia, Xiaotian Zhang, Wei Chen, Hai Cheng, Kunming Qi, Feng Zhu, Fan Xia, Lili Zhu, Hujun Li, Huanxin Zhang, Dongmei Yan, Tingting Qiu, Yanlei Zhang, Shuixiu Peng, Wei Sang, Depeng Li, Alex H Chang, Bin Pan, Zhiling Yan; Anti-BCMA/GPRC5D CAR T in relapsed or refractory multiple myeloma patients with extraosseous extramedullary disease. Blood 2026; blood.2026033506. doi: https://doi.org/10.1182/blood.2026033506 (https://ashpublications.org/blood/article/doi/10.1182/blood.2026033506/568612/Anti-BCMA-GPRC5D-CAR-T-in-relapsed-or-refractory)

 
Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial — Journal of Clinical Oncology (May 2026)

What is the purpose of the study? 
To evaluate serum mass spectrometry (MS)-based measurable residual activity (MRA) in multiple myeloma (MM) using samples from the phase III GMMG-HD7 trial. The aim is to assess the analytical performance of MS and its association with clinical outcomes, and to compare its prognostic and complementary value relative to serum-based assays and bone-marrow measurable residual disease (MRD).

Summary  
A total of 3,301 serum samples from 617 patients in the GMMG-HD7 trial were analyzed to evaluate MS-based detection and longitudinal tracking of monoclonal (M) proteins. MS showed high analytical sensitivity for detecting low-level M protein and provided improved detection compared with serum protein electrophoresis (SPEP), while also allowing differentiation of M proteins from therapeutic monoclonal antibodies in analytic measurements. MS negativity was associated with improved progression-free survival (PFS), most notably at 12 months of maintenance therapy (hazard ratio 0.25, 95% CI 0.15–0.43; adjusted P < .001), and combined assessment with bone-marrow MRD identified distinct prognostic groups with poorest outcomes in patients positive by both methods.

Strengths 
• Large prospective dataset from the phase III GMMG-HD7 trial (617 patients; 3,301 samples) 
• High analytical sensitivity for low-level monoclonal protein detection compared with SPEP 
• Ability to longitudinally track M protein dynamics across treatment phases 
• Clear association between MS negativity and improved progression-free survival (PFS) 
• Strong prognostic separation when combined with bone-marrow MRD assessment, particularly identifying high-risk (MS/MRD double-positive) and low-risk (double-negative) groups

Limitations 
• No established standardized thresholds for defining biochemical relapse using MS measurements 
• Limited long-term follow-up for some survival and response subgroups 
• Early discordance between MS and MRD, especially in IgG-type multiple myeloma, likely influenced by immunoglobulin pharmacokinetics (e.g., FcRn-mediated recycling and longer serum half-life), complicating early interpretation of residual disease 
• Reduced prognostic discrimination of MS in patients already achieving complete response at current follow-up

Why this study matters 
Serum MS-based measurable residual activity is a sensitive and reproducible biomarker that provides clinically relevant prognostic information in multiple myeloma and complements bone-marrow MRD assessment. Its strongest utility lies in identifying deep residual disease and refining risk stratification when combined with MRD, particularly for distinguishing high- and low-risk patient groups. Further longitudinal follow-up and standardized interpretive criteria are needed before incorporation into routine response and relapse frameworks.

Reference: 
Jia xiang Jin et al. Peripheral Measurable Residual Disease Activity Assessment by MALDI-TOF Mass Spectrometry in Patients With Newly Diagnosed Multiple Myeloma in the Phase III GMMG-HD7 Trial. J Clin Oncol 0, JCO-25-02957 DOI:10.1200/JCO-25-02957 (https://ascopubs.org/doi/10.1200/JCO-25-02957)

FDG-PET medullary total tumor volume highlights high-risk patients with newly diagnosed multiple myeloma in CASSIOPEIA trial — Blood Advances (May 2026)

What is the purpose of the study? 
To evaluate the prognostic value of medullary total metabolic tumor volume (mTMTV) derived from baseline [18F]FDG-PET/CT in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab as part of induction, consolidation, and/or maintenance therapy in the CASSIOPET study. It compares mTMTV with conventional PET-derived parameters and the Revised International Staging System (R-ISS) for predicting progression-free survival (PFS) and overall survival (OS).

Summary  
The analysis included 195 patients with NDMM enrolled in CASSIOPET, a companion study of CASSIOPEIA, using baseline [18F]FDG-PET/CT with automated bone/liver segmentation to derive mTMTV, which incorporates both focal lesions and diffuse bone marrow involvement. In multivariate Cox analysis, higher mTMTV demonstrated independent prognostic value for PFS and OS and provided information complementary to R-ISS. Machine learning models identified mTMTV as the most informative PET-derived feature for both PFS and OS, alongside other imaging and clinical variables.

Key points 
• mTMTV showed independent prognostic value for PFS and OS in NDMM
• mTMTV provided prognostic information complementary to R-ISS
• Machine learning models identified mTMTV as the most informative PET-derived feature for both PFS and OS
• Inclusion of diffuse bone marrow metabolic activity contributed to the prognostic value of mTMTV compared with focal-lesion-only approaches

Strengths 
• Prospective cohort design with 195 patients and long-term follow-up
• Combined use of multivariate Cox regression and machine learning survival models 
• Automated PET segmentation reduced inter-observer variability
• Integration of imaging biomarkers with established clinical staging (R-ISS).

Limitations 
• Lack of newer high-risk cytogenetic abnormalities (e.g., TP53 mutations, 1q alterations) in risk modeling. 
• External validation in independent cohorts remains necessary. 
• Standardization of PET-derived thresholds and segmentation methods across centers is still required.

Why this study matters 
In this prospective cohort, baseline [18F]FDG-PET/CT–derived mTMTV demonstrated independent prognostic value for progression-free and overall survival in patients with newly diagnosed multiple myeloma treated with daratumumab-based therapy. It provided prognostic information complementary to R-ISS and was consistently identified as the most informative PET-derived feature in machine learning models. These findings support further validation of mTMTV for potential use in baseline risk stratification.

Reference: 
Bastien Jamet, Shamimeh Ahrari, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, Emmanuel Itti, Lionel Karlin, Clément Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Diana Mateus, Philippe Moreau, Cyrille Touzeau, Françoise Kraeber-Bodéré, Thomas Carlier; FDG-PET medullary total tumor volume highlights high-risk patients with newly diagnosed multiple myeloma in CASSIOPEIA trial. Blood Adv 2026; 10 (11): 3787–3798. doi: https://doi.org/10.1182/bloodadvances.2025019465 (https://ashpublications.org/bloodadvances/article/10/11/3787/567465/FDG-PET-medullary-total-tumor-volume-highlights)

Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma — Science Translational Medicine (May 2026)

What is the purpose of the study? 
To evaluate the safety, feasibility, manufacturing speed, and preliminary efficacy of durcabtagene autoleucel, a B cell maturation antigen (BCMA)-directed CAR T cell therapy, in patients with relapsed/refractory multiple myeloma (RRMM). The study also examined whether a rapid manufacturing platform could preserve stem-like T cell characteristics during CAR T cell production.

Summary 
In this open-label, multicenter phase 1 trial (NCT04318327), 55 heavily pretreated patients with relapsed/refractory multiple myeloma received durcabtagene autoleucel, an autologous BCMA-targeted CAR T cell therapy manufactured in fewer than 2 days with a median vein-to-vein time of 24 days. Across four dose levels, the overall response rate was 98%, the stringent complete response rate was 55%, and 80% of evaluable patients (35/44) achieved minimal residual disease (MRD) negativity. Median progression-free survival was 12 months after a median follow-up of 20 months.

Safety findings were generally consistent with known toxicities associated with CAR T cell therapies. All but one patient experienced cytokine release syndrome (CRS), which was managed with standard supportive measures, and no delayed neurotoxicity or Parkinsonian-like events were reported during follow-up. Laboratory and transcriptomic analyses suggested preservation of stem-like and less differentiated T cell characteristics in the manufactured product.

Key points 
• Phase 1, open-label, multicenter dose-escalation trial in patients with RRMM 
• Investigational therapy: durcabtagene autoleucel, a BCMA-directed CAR T cell therapy
• Clinical trial identifier: NCT04318327
• 55 patients underwent successful manufacturing and received infusion
• Median vein-to-vein time: 24 days, with some cases as short as 15 days
• Manufacturing process required fewer than 2 days and avoided prolonged ex vivo expansion
• Overall response rate (ORR): 98%
• Stringent complete response (sCR) rate: 55%
• MRD negativity achieved in 80% of evaluable patients (35/44)
• Median progression-free survival (PFS): 12 months after a median follow-up of 20 months
• CRS occurred in nearly all patients and was managed with supportive care
• No delayed neurotoxicity or Parkinsonian-like toxicities were reported during the study's follow-up period
• Cellular analyses showed preservation of stem-like and naive-like T cell phenotypes in the final product 
• A phase 2 study (NCT05172596) was initiated based on phase 1 findings

Strengths 
• Rapid manufacturing platform was associated with a shorter median vein-to-vein time than timelines reported in real-world studies of currently available BCMA CAR T therapies. 
• Included heavily pretreated and high-risk patients, including patients with adverse cytogenetics and extramedullary disease. 
• Integrated translational analyses, including flow cytometry and single-cell RNA sequencing, to evaluate T cell phenotype and stemness-related signatures. 
• Manufacturing success rate was 100% in the trial population.

Limitations 
• Small sample size (55 patients), limiting precision of efficacy and safety estimates. 
• Multiple dose levels were evaluated, complicating dose-specific interpretation. 
• Heterogeneous patient population and prior treatments may affect interpretation of outcomes. 
• Median follow-up of 20 months limits conclusions regarding long-term durability and late toxicities. 
• Cross-trial comparisons with other CAR T therapies such as ide-cel and cilta-cel are limited by differences in study design and patient characteristics.

Why this study matters 
In this phase 1 study, durcabtagene autoleucel demonstrated high response rates and substantial MRD negativity in heavily pretreated patients with RRMM while using a rapid CAR T manufacturing platform with a median 24-day vein-to-vein time. The treatment showed a safety profile generally consistent with BCMA-directed CAR T cell therapies, without reported delayed neurotoxicity or Parkinsonian-like events during the observed follow-up period. These findings support further evaluation of durcabtagene autoleucel in phase 2 testing.

Reference: 
Adam S. Sperling et al. Efficacy and safety of durcabtagene autoleucel in a phase 1 trial for patients with relapsed/refractory multiple myeloma.Sci. Transl. Med.18,eadx1799(2026). DOI:10.1126/scitranslmed.adx1799 (https://www.science.org/doi/10.1126/scitranslmed.adx1799)

 
Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy — New England Journal of Medicine (May 2026)

What is the purpose of the study? 
To evaluate whether teclistamab, a bispecific antibody targeting B-cell maturation antigen (BCMA) and CD3, improves outcomes compared with standard treatment regimens in patients with relapsed or refractory multiple myeloma who had received 1–3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide.

Summary 
In this clinical trial A total of 593 patients with relapsed or refractory multiple myeloma (RRMM) were randomly assigned to receive either teclistamab (296 patients) or the investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) (297 patients). After a median follow-up of 17.3 months, teclistamab significantly improved progression-free survival, with an estimated 18-month progression-free survival rate of 69.8% compared with 26.9% for PVd or Kd (hazard ratio [HR] for disease progression or death, 0.29; 95% confidence interval [CI], 0.23–0.38; P<0.001). Complete response or better occurred in 65.9% of patients receiving teclistamab compared with 16.8% of those receiving PVd or Kd (P<0.001).

Teclistamab also improved overall survival, with estimated 18-month overall survival rates of 79.2% versus 68.6% (HR for death, 0.60; 95% CI, 0.43–0.83; P=0.002). Grade 3–4 adverse events occurred in 84.9% of patients receiving teclistamab and 76.3% of those receiving PVd or Kd, while grade 5 adverse events occurred in 6.5% and 3.5%, respectively. Grade 3–4 infections occurred in 41.6% and 29.0% of patients, respectively. Cytokine release syndrome occurred in 66.0% of teclistamab-treated patients, with most events being grade 1 or 2, and immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 4.1%.

Key points

Most important findings 
• Phase 3 randomized trial in patients with RRMM after 1–3 prior lines of therapy. 
• Compared teclistamab with investigator’s choice of PVd (pomalidomide, bortezomib, dexamethasone) or Kd (carfilzomib, dexamethasone). 
• Estimated 18-month progression-free survival: 
 - Teclistamab: 69.8% 
 - PVd/Kd: 26.9% 
 - HR for disease progression or death: 0.29 (95% CI, 0.23–0.38; P<0.001).

• Complete response or better: 
 - Teclistamab: 65.9% 
 - PVd/Kd: 16.8% (P<0.001).

• Estimated 18-month overall survival: 
 - Teclistamab: 79.2% 
 - PVd/Kd: 68.6% 
 - HR for death: 0.60 (95% CI, 0.43–0.83; P=0.002).

Safety findings 
• Grade 3–4 adverse events: 
 - Teclistamab: 84.9% 
 - PVd/Kd: 76.3%

• Grade 5 adverse events: 
 - Teclistamab: 6.5% 
 - PVd/Kd: 3.5%

• Grade 3–4 infections: 
 - Teclistamab: 41.6% 
 - PVd/Kd: 29.0%

• Cytokine release syndrome occurred in 66.0% of teclistamab-treated patients, with most events being grade 1–2. 
• ICANS occurred in 4.1% of teclistamab-treated patients. 

Strengths 
• Randomized phase 3 study design. 
• Large study population (593 patients). 
• Independent review committee assessment of the primary endpoint. 
• Demonstrated statistically significant improvements in progression-free survival, overall survival, and complete response rates.

Limitations 
• Results are based on an interim analysis with a median follow-up of 17.3 months. 
• The interim analysis does not provide information on longer-term efficacy and safety outcomes. 
• Higher rates of grade 3–4 infections and adverse events were observed with teclistamab.

Why this study matters 
In patients with RRMM who had received 1–3 prior lines of therapy, teclistamab significantly improved progression-free survival and overall survival and increased complete response rates compared with PVd or Kd. Grade 3–4 infections and other severe adverse events were more common with teclistamab. These findings showed longer progression-free survival, longer overall survival, and higher response rates with teclistamab than with PVd or Kd during the reported follow-up period, alongside a higher incidence of grade 3–4 infections.

Reference: 
Touzeau C, Mina R, Quach H, Hungria V, Bhutani D, Chen W, Kumar S, Chaulagain C, Dimopoulos MA, Bahlis NJ, Maral S, van de Donk NWCJ, Schmidt Filho J, Saja K, Teipel R, Ando M, Roeloffzen W, Annibali O, Augustson B, Botta C, Delforge M, Bourgeois E, Buda G, Hus M, Perrot A, Preis M, Beksac M, Pour L, Farmer S, Nunes M, Oriol A, Melchardt T, Hu Y, Flogegård M, Wang D, Pei L, Wroblewski S, Ariës IM, Quijano Cardé NA, Perova T, de Jager T, Yeh TM, Vanquickelberghe V, Shah P, Chastain K, Kobos R, Carson R, Landgren O; MajesTEC-9 Trial Investigators. Teclistamab in Multiple Myeloma with One to Three Previous Lines of Therapy. N Engl J Med. 2026 May 29. doi: 10.1056/NEJMoa2603870. (https://www.nejm.org/doi/10.1056/NEJMoa2603870)

Arlocabtagene autoleucel - a GPRC5D-targeted CAR T-cell therapy in heavily pretreated relapsed/refractory multiple myeloma — Blood (June 2026)

What is the purpose of the study? 
This phase 1 clinical trial (NCT04674813) evaluates the safety, tolerability, and preliminary efficacy of arlocabtagene autoleucel (arlo-cel, BMS-986393), a GPRC5D-targeted CAR T-cell therapy, in adults with heavily pretreated relapsed or refractory multiple myeloma (RRMM). The study also assesses the maximum tolerated dose (MTD), treatment responses, and survival outcomes.

Summary 
This phase 1 dose-escalation and expansion clinical trial (NCT04674813) enrolled 84 adults with RRMM who had received at least three prior antimyeloma treatment regimens, including an immunomodulatory drug (IMiD), a proteasome inhibitor, and an anti-CD38 antibody. Patients had received a median of five prior treatment regimens, and 49% had previously received BCMA-targeted therapy, including 38% who had received prior CAR T-cell therapy. Arlo-cel was administered as a single intravenous infusion at doses ranging from 25×10⁶ to 450×10⁶ CAR T cells.

At a median follow-up of 16.1 months, the overall response rate (ORR) was 87% in the efficacy analysis population (n=79), including a complete response rate of 53%. Median duration of response was 18.0 months, median progression-free survival (PFS) was 18.3 months (95% CI, 11.8–21.9), and the 1-year overall survival (OS) rate was 90%. Cytokine release syndrome (CRS) occurred in 82% of patients, immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 10%, and other selected neurotoxicities occurred in 12%; most events were grade 1 or 2. One CRS-related death occurred at the highest dose level, and the MTD was not reached.

Key points

Efficacy 
• ORR was 87% in the efficacy analysis population (n=79) 
• Complete response rate was 53%
• Median duration of response was 18.0 months
• Median PFS was 18.3 months (95% CI, 11.8–21.9)
• The 1-year OS rate was 90%

Safety 
• CRS occurred in 82% of patients; most cases were grade 1/2
• ICANS occurred in 10% of patients 
• Other selected neurotoxicities occurred in 12% of patients
• One treatment-related death from CRS occurred at the highest dose level
• On-target/off-tumor adverse events affecting the skin (30%), oral tissues (32%), and nails (19%) were generally transient, grade 1/2, and most resolved without intervention
• MTD was not reached

Strengths 
• Included a heavily pretreated RRMM population with a median of five prior treatment regimens. 
• 49 percent of patients had received prior BCMA-targeted therapy, including 38% who had received prior CAR T-cell therapy. 
• Median follow-up was 16.1 months

Limitations 
• Phase 1, non-randomized study without a control group
• Relatively small sample size (84 patients)
• The frequency of CRS and selected neurotoxicities appeared dose dependent
• One CRS-related death occurred at the highest dose level

Why this study matters 
In this phase 1 study of 84 patients with heavily pretreated RRMM, arlocabtagene autoleucel was associated with an overall response rate of 87%, a complete response rate of 53%, median duration of response of 18.0 months, median progression-free survival of 18.3 months, and a 1-year overall survival rate of 90%. Cytokine release syndrome and neurotoxicity were common but were predominantly grade 1/2, although one CRS-related death occurred at the highest dose level. The findings provide phase 1 safety and efficacy data for arlo-cel in this patient population.

Reference: 
Susan Bal, Myo Htut, Omar Nadeem, Larry D. Anderson, Tara Gregory, Mehmet Kocoglu, Adriana C Rossi, Tom G Martin, Daniel Nathan Egan, Luciano J. Costa, Hongxiang Hu, Jinjie Chen, Shaoyi Li, Lisa M Kelly, Naomey Sarkis, Safiyyah Ziyad, Kristina M Jordahl, Wei-Ming Kao, Allison June Kaeding, Michael R. Burgess, Jesus G Berdeja; Arlocabtagene autoleucel-a GPRC5D-targeted CAR T-cell therapy in heavily pretreated relapsed/refractory multiple myeloma. Blood 2026; blood.2025030750. doi: https://doi.org/10.1182/blood.2025030750 (https://ashpublications.org/blood/article/doi/10.1182/blood.2025030750/568830/Arlocabtagene-autoleucel-a-GPRC5D-targeted-CAR-T)

Daratumumab in Transplant-Ineligible or -Deferred Newly Diagnosed Multiple Myeloma: Minimal Residual Disease in CEPHEUS — Blood Advances (June 2026)

What is the purpose of the study? 
To evaluate whether adding daratumumab to bortezomib/lenalidomide/dexamethasone (D-VRd) improves measurable residual disease (MRD) negativity compared with VRd. The study analyzes its association with progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) who were transplant-ineligible or deferred transplant.

Summary 
A total of 395 patients with NDMM were randomized to receive either D-VRd (n=197) or VRd (n=198). After a median follow-up of 58.7 months, D-VRd resulted in higher rates of overall MRD negativity than VRd at both the 10⁻⁵ threshold (60.9% vs 39.4%; OR 2.37, 95% CI 1.58–3.55; P<0.0001) and the 10⁻⁶ threshold (46.2% vs 27.3%; OR 2.24, 95% CI 1.48–3.40; P=0.0001). Sustained MRD negativity lasting at least 12 months was also higher with D-VRd (49.2% vs 27.3% at 10⁻⁵; 34.0% vs 16.2% at 10⁻⁶; both P<0.0001). The abstract reports improved progression-free survival in the intent-to-treat population with D-VRd versus VRd.

Key points 
• Study design: Phase 3 randomized trial in transplant-ineligible or transplant-deferred patients with newly diagnosed multiple myeloma. 
• Participants: 395 patients randomized 1:1 to D-VRd (n=197) or VRd (n=198). 
• Primary endpoint: MRD negativity among patients achieving at least a complete response (≥CR), assessed by next-generation sequencing at the 10⁻⁵ sensitivity threshold. 
• Overall MRD negativity: 
 - 10⁻⁵: 60.9% (D-VRd) vs 39.4% (VRd); OR 2.37 (95% CI 1.58–3.55); P<0.0001. 
 - 10⁻⁶: 46.2% (D-VRd) vs 27.3% (VRd); OR 2.24 (95% CI 1.48–3.40); P=0.0001.

• Sustained MRD negativity ≥12 months: 
 - 10⁻⁵: 49.2% vs 27.3%. 
 - 10⁻⁶: 34.0% vs 16.2%. 
 - Both comparisons were statistically significant (P<0.0001).

• Progression-free survival: The abstract reports improved progression-free survival in the overall intent-to-treat population with D-VRd versus VRd. Among patients who achieved MRD negativity, PFS numerically favored D-VRd but was not statistically significant (10⁻⁵ HR 0.61, 95% CI 0.35–1.06, P=0.0755; 10⁻⁶ HR 0.66, 95% CI 0.31–1.41, P=0.2811)

• MRD durability: Higher sustained MRD-negativity rates with D-VRd were also observed at ≥24- and ≥36-month assessments

• Follow-up: Median follow-up was 58.7 months

Strengths 
• Phase 3 randomized study design
• Long median follow-up of 58.7 months
• Comprehensive assessment of MRD at highly sensitive thresholds (10⁻⁵ and 10⁻⁶)
• Evaluation of both overall and sustained MRD negativity over time.

Limitations 
• The abstract does not provide detailed safety or tolerability results. 
• PFS analyses among patients who achieved MRD negativity were not statistically significant. 
• Overall survival results were not described in the provided abstract. 
• The available information is limited to the abstract and does not include detailed subgroup, safety, or methodological data.

Why this study matters 
In the phase 3 CEPHEUS study, D-VRd produced higher rates of overall and sustained MRD negativity than VRd in transplant-ineligible or transplant-deferred patients with newly diagnosed multiple myeloma. The abstract reports improved progression-free survival in the intent-to-treat population with D-VRd versus VRd after a median follow-up of 58.7 months. Among patients who achieved MRD negativity, progression-free survival numerically favored D-VRd, although these analyses were not statistically significant.

Reference: 
Sonja Zweegman, Thierry Facon, Vania Hungria, Nizar J. Bahlis, Christopher P. Venner, Marc Braunstein, Ludek Pour, Josep Marti, Supratik Basu, Yael C. Cohen, Morio Matsumoto, Kenshi Suzuki, Cyrille Hulin, Wojciech Maciej Legiec, Meral Beksac, Angelo Maiolino, Hiroyuki Takamatsu, Aurore Perrot, Mehmet Turgut, Weiping Liu, Jianping Wang, Emilie Van Brummelen, Maria Krevvata, Lorena Lopez-Masi, Jodi Carey, Fredrik Borgsten, Melissa Rowe, Robin Carson, Saad Z. Usmani; Daratumumab in Transplant-Ineligible or -Deferred Newly Diagnosed Multiple Myeloma: Minimal Residual Disease in CEPHEUS. Blood Adv 2026; bloodadvances.2026019937. doi: https://doi.org/10.1182/bloodadvances.2026019937 (https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2026019937/568868/Daratumumab-in-Transplant-Ineligible-or-Deferred)

 
Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma: dynamics of MRD negativity in the IMROZ study — Blood (June 2026)

What is the purpose of the study? 
This analysis of the phase 3 IMROZ study evaluates how minimal residual disease (MRD) status changes over time in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) treated with isatuximab-based quadruplet therapy (Isa-VRd followed by Isa-Rd) versus standard VRd followed by Rd. The study assesses the relationship between MRD negativity, MRD-negative complete response (CR), and clinical outcomes over approximately 60 months of follow-up.

Summary 
In the randomized phase 3 IMROZ study, transplant-ineligible patients with NDMM received either Isa-VRd (isatuximab, bortezomib, lenalidomide, and dexamethasone) followed by Isa-Rd maintenance or VRd followed by Rd. Landmark analyses showed that Isa-VRd/Isa-Rd was associated with higher rates of MRD negativity and MRD-negative CR at the end of induction and throughout maintenance, with higher MRD negativity rates observed with Isa-VRd/Isa-Rd across key subgroups, including patients older than 70 years and frail patients.

The isatuximab-based regimen was also associated with lower rates of conversion from MRD-negative to MRD-positive status and longer time to progression (TTP) among patients who experienced MRD conversion. Sustained MRD negativity rates were higher with Isa-VRd/Isa-Rd than with VRd/Rd, including sustained MRD negativity for ≥12 months (46.8% vs 24.3%) and ≥24 months (35.8% vs 13.3%). These findings extend prior IMROZ results showing MRD negativity at any time point of 58.1% versus 43.6%, respectively. The analysis also found that MRD-negative patients who achieved complete response had significantly improved progression-free survival (PFS).

Key points

Main findings 
• Isa-VRd followed by Isa-Rd was associated with: 
 - Higher MRD negativity rates than VRd/Rd. 
 - Higher MRD-negative complete response (CR) rates during induction and maintenance. 
 - Higher rates of sustained MRD negativity over time.

• Higher MRD negativity rates with Isa-VRd/Isa-Rd were observed across important patient subgroups, including: 
 - Patients >70 years of age 
 - Frail patients

• Conversion from MRD negativity to MRD positivity occurred less frequently with Isa-VRd/Isa-Rd. 
• Among patients who became MRD positive after initially achieving MRD negativity, time to progression was longer with Isa-VRd/Isa-Rd. 
• MRD-negative patients who achieved CR had significantly improved progression-free survival. 
• Some patients achieved MRD negativity several years after treatment initiation, indicating that MRD status may continue to evolve during prolonged treatment.

Important numerical results 
• MRD negativity at any time point (10⁻⁵ sensitivity): 
 - Isa-VRd/Isa-Rd: 58.1% 
 - VRd/Rd: 43.6%

• Sustained MRD negativity ≥12 months: 
 - Isa-VRd/Isa-Rd: 46.8% 
 - VRd/Rd: 24.3%

• Sustained MRD negativity ≥24 months: 
 - Isa-VRd/Isa-Rd: 35.8% 
 - VRd/Rd: 13.3% 

Strengths 
• Randomized phase 3 study design. 
• Long follow-up period of approximately 60 months. 
• Detailed evaluation of MRD dynamics over multiple time points. 
• Included clinically relevant subgroups such as older and frail patients. 
• Assessed both the depth and persistence of MRD responses.

Limitations 
• The mechanisms underlying sustained MRD negativity and later conversion to MRD positivity remain uncertain. 
• The specific contribution of individual treatment components, particularly bortezomib, could not be determined from these analyses. 
• Additional studies are needed to better understand biological factors associated with MRD dynamics and to evaluate MRD-guided treatment strategies.

Why this study matters 
In this long-term analysis of the IMROZ study, Isa-VRd followed by Isa-Rd was associated with higher rates of MRD negativity, MRD-negative CR, and sustained MRD negativity than VRd/Rd. Among patients who converted from MRD-negative to MRD-positive status, time to progression was longer with Isa-VRd/Isa-Rd than with VRd/Rd, and MRD-negative patients who achieved CR had significantly improved progression-free survival. The findings suggest that assessment of MRD at multiple time points may help inform treatment decisions and further characterize long-term MRD and progression-related outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma.

Reference: 
Robert Z. Orlowski, Meletios A. Dimopoulos, Xavier Leleu, Thierry Facon, Tadao Ishida, Roman Hájek, Ivan Špička, Joanna Romejko-Jarosinska, Vladimir Vorobyev, Britta Besemer, Sevgi Kalayoğlu Beşışık, Pawel Robak, Tomas Jelinek, Hartmut Goldschmidt, Thomas Martin, Mohamad Mohty, Sandrine Macé, Ercem Kodas, Christina Tekle, Andrea T. Shafer, Philippe Moreau; Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma: dynamics of MRD negativity in the IMROZ study. Blood 2026; 147 (23): 2760–2769. doi: https://doi.org/10.1182/blood.2025030120 (https://ashpublications.org/blood/article/147/23/2760/566876/Isatuximab-bortezomib-lenalidomide-and)
 

European Commission

EU approves subcutaneous isatuximab: The first myeloma treatment via on-body injector

On Monday, June 8, Sanofi announced in a press release (https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-08-05-00-00-3307781) that “the European Commission has approved Sarclisa (isatuximab) subcutaneous (SC) in combination with standard-of-care regimens for the treatment of patients with multiple myeloma across all existing indications for Sarclisa intravenous (IV) formulation.”  

Administered via the CirCLIQ® OBI, isatuximab “offers a treatment experience designed around the needs of patients and HCPs and enables flexible administration in either home or outpatient settings,” Sanofi further added.

Since its launch in 2020, isatuximab has been approved in the EU across four indications in myeloma. The IV formulation is approved in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for both transplant-ineligible and transplant-eligible newly diagnosed multiple myeloma (NDMM), as well as with pomalidomide and dexamethasone (Pd) or carfilzomib and dexamethasone (Kd) for relapsed/refractory myeloma (RRMM).  

Approval of the subcutaneous (SC) formulation was supported by results from the pivotal phase 3 IRAKLIA study and additional clinical studies. In IRAKLIA, isatuximab SC demonstrated non-inferior efficacy compared with the IV formulation in patients with RRMM. The approval followed a positive opinion from the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP).

The phase 3 IRAKLIA and phase 2 IZALCO studies evaluated the SC administration of isatuximab using an OBI. In IRAKLIA, 70% of patients receiving isatuximab SC via OBI reported being satisfied or very satisfied with treatment administration, compared with 53.4% of patients receiving intravenous (IV) isatuximab, while IZALCO found that 74.5% of patients preferred OBI administration over manual injection and 8.5% preferred manual injection. The OBI, Enable Injections’ enFuse-powered CirCLIQ® device, delivers isatuximab SC through a hidden, retractable needle and is designed for use in outpatient or home settings.

In IRAKLIA, isatuximab SC administered via OBI in combination with pomalidomide and dexamethasone (Pd) achieved an objective response rate (ORR) of 71.3%, compared with 70.5% for IV Sarclisa-Pd, meeting the predefined criterion for non-inferiority in adults with RRMM who had received at least one prior line of therapy. The safety profile of isatuximab SC-Pd was generally consistent with that of IV Isa-Pd, with systemic infusion reactions occurring in 1.5% of patients receiving SC treatment versus 25% with IV treatment. No new safety signals were identified, although low-grade injection-site reactions occurred in 1.4% of OBI injections and were mostly grade 1, with one reported grade 2 event.

Currently, isatuximab is the only anti-CD38 monoclonal antibody in multiple myeloma that offers the flexibility of both SC OBI and administration through manual injection.

Reference: 
Sanofi’s Sarclisa subcutaneous approved in the EU as the first anticancer treatment administered via an on-body injector. (https://www.sanofi.com/en/media-room/press-releases/2026/2026-06-08-05-00-00-3307781) Sanofi press release. June 8, 2026. 

For the latest, up-to-the-minute news on multiple myeloma, visit the IMF Newsroom.  (https://www.myeloma.org/news-events/multiple-myeloma-news)