At the 2026 European Hematology Association (EHA) Annual Meeting, Professor Niels van de Donk from the Amsterdam University Medical Center (Amsterdam UMC), representing the EMN30 study group, announced the updated safety run-in (SRI) results of the EMN30/MAJESTEC-4 study. This study aims to evaluate the safety and preliminary efficacy of the BCMA×CD3 bispecific antibody Teclistamab (Tec), either as monotherapy or in combination with Lenalidomide (Len), as maintenance therapy for patients with newly diagnosed multiple myeloma (NDMM) following autologous stem cell transplantation (ASCT).01 Clinical Challenges and Research Background: Urgent Need to Break the “Ceiling” of Maintenance Therapy
Lenalidomide monotherapy following ASCT is the current standard of care (SoC) for NDMM patients. Although this regimen significantly extends progression-free survival (PFS), a large number of patients eventually face relapse. Professor Niels van de Donk pointed out that the presence of minimal residual disease (MRD) in NDMM patients after transplantation is the root cause of relapse. Teclistamab, as a first-in-class BCMA×CD3 bispecific antibody, redirects T cells to kill BCMA-positive plasma cells and has demonstrated potent activity in relapsed/refractory multiple myeloma (RRMM). The core logic of the MAJESTEC-4 study is to move this potent immunotherapy forward to the maintenance phase, either in combination with or as a replacement for Lenalidomide, to clear residual disease and achieve deeper survival benefits.
02 Innovative Study Design: Exploring Optimal Maintenance Regimens through Cohorts
EMN30/MAJESTEC-4 is a randomized, open-label, Phase III clinical study. The safety run-in (SRI) results reported here include three cohorts of NDMM patients who received 4-6 cycles of induction therapy and ASCT and achieved at least a partial response (≥PR). • Cohort 1: Teclistamab (Intensive dosing: weekly until Cycle 3, then every 2 weeks until Cycle 6, and monthly from Cycle 7 onwards) + Lenalidomide (10 mg). • Cohort 2: Teclistamab (Simplified dosing: monthly starting from Cycle 2) + Lenalidomide (10 mg). • Cohort 3: Teclistamab (monthly) monotherapy. Key Design Point: To reduce the risk of overlapping cytokine release syndrome (CRS) and myelosuppression, Lenalidomide initiation in the combination cohorts (Cohorts 1 & 2) was delayed until Cycle 2, past the CRS risk window of Teclistamab. Additionally, the study implemented a fixed-duration maintenance (2 years), with the option to stop Teclistamab after 1 year of combination therapy if a complete response (CR) or better was achieved.
03 Safety Analysis: Balancing Hematologic Toxicity and Infection Risk
The data covers results with a median follow-up of approximately 3 years (Cohort 1) and approximately 2 years (Cohorts 2 & 3). Hematologic Safety: • Neutropenia: Grade 3/4 neutropenia was most common in the intensive regimen (Cohort 1) at 94%. It decreased to 78% in the simplified regimen (Cohort 2) and was 63% with Teclistamab monotherapy (Cohort 3). • Thrombocytopenia and Anemia: Grade 3/4 events were observed very rarely, demonstrating good bone marrow tolerance. Non-Hematologic Safety: • CRS: The overall incidence was 40%-50%, with the vast majority being Grade 1 events. The incidence of Grade 2 CRS was only 6.4%, and no Grade 3 or higher CRS was observed. These figures are significantly better than the incidence observed in the RRMM late-line setting, suggesting that the stable immune microenvironment post-transplant may reduce the risk of hypersensitivity reactions to the bispecific antibody. • Infections: Grade 3 or higher infections were seen in approximately one-third of patients in Cohorts 1 and 2, and 26% in Cohort 3. • Immunoglobulin Management: Hypogammaglobulinemia was observed in almost all patients; therefore, intravenous immunoglobulin (IVIG) replacement therapy was strongly recommended and implemented. • Special Event: One Grade 5 (fatal) neurological event was reported. The patient developed progressive neurological deficits while traveling in Australia. Despite extensive workup including MRI, PET-CT, and CSF analysis for viruses (with Creutzfeldt-Jakob disease as a differential diagnosis), no definitive underlying cause was found. However, based on the principle of caution, the hospital team deemed the disorder potentially related to the Tec + Len treatment.
04 Remarkable Efficacy: Continuous Evolution of MRD Negativity Rates and Remission Depth
The study demonstrated the extraordinary ability of Teclistamab maintenance to deepen response depth. Improvement in Response Rates: • Cohort 1: CR rate was 46% at enrollment (post-transplant) and increased to 100% during maintenance. • Cohort 2: CR rate was 41% after transplant and increased to 97% during maintenance. • Cohort 3: CR rate was 60% at enrollment and increased to 97%. MRD Negativity Rate (Threshold 10^{-5}): Evaluated using Next-Generation Flow (NGF), Teclistamab showed potent disease-clearing capacity. • In Cohorts 1 and 2, the MRD negativity rate was 33% at enrollment but climbed to 100% at 12 months of maintenance. • In Cohort 3 (monotherapy), the MRD negativity rate also increased from enrollment to 12 months, from 44% to 90%. Survival Benefit Projection: Although the follow-up time is still short, preliminary PFS data are encouraging. The estimated 18-month and 24-month PFS rates range between 94% and 97%, with only 3 progression events observed across all SRI patients.
05 Expert Insights and Future Outlook: Can Bispecifics Challenge the Status of Transplantation?
During the Q&A session, Professor Niels van de Donk engaged in an in-depth discussion on clinical focal points: Q: Is there a difference in MRD negativity kinetics between standard-risk and high-risk patients? Professor Donk noted: Data show that the onset of Teclistamab is extremely rapid and profound. The majority of patients, whether standard-risk or those with high-risk cytogenetic abnormalities (representing about 1/4 of the enrolled population), achieved MRD negativity within 12 months. This suggests that bispecific antibodies may overcome the resistance associated with high-risk genetics through potent T-cell redirection mechanisms. Q: Will Teclistamab maintenance replace ASCT or change first-line induction regimens? Professor Donk believes: Currently, the MAJESTEC-4 study validates the maintenance value of bispecifics post-ASCT. However, as the German study group demonstrated that the Tec-DR regimen (Teclistamab + Daratumumab + Revlimid, etc.) achieves extremely high MRD negativity rates during induction, a “transplant-free” pathway may exist in the future. The randomized Phase III portion of MAJESTEC-4 is further comparing Tec ± Len versus Len monotherapy, and its results will ultimately determine if this regimen can rewrite global guidelines. Q: How is immune function recovery after discontinuation? Professor Donk responded: Since BCMA bispecifics clear plasma cells, immune recovery after discontinuation is highly individualized; for some patients, it may take up to a year to reconstitute humoral immunity. Therefore, continuous IVIG support and infection monitoring are crucial after the fixed-duration treatment ends.
Conclusion
The SRI results of the EMN30/MAJESTEC-4 study confirm the excellent safety and superior efficacy of Teclistamab as a component of NDMM maintenance therapy. The monthly dosing schedule ensures efficacy while greatly improving patient convenience. In particular, the CR rate of up to 100% and near-complete MRD negativity rate herald a transition into the era of “precision clearance” for MM maintenance therapy. Currently, the randomized Phase III portion of the study is underway across multiple global centers. We look forward to the final PFS and overall survival (OS) data to provide more potent and durable remission options for NDMM patients in China and worldwide.
