Elranatamab in Combination With Daratumumab and Lenalidomide (EDR) in Transplant-Ineligible (TI) Patients With Newly Diagnosed Multiple Myeloma (NDMM): Results From MagnetisMM-6 Part 1
Background:
MagnetisMM-6 (NCT05623020) is a phase 3, open-label, randomized study evaluating EDR versus daratumumab+bortezomib+lenalidomide+dexamethasone in patients with TI NDMM. Part 1 identified dose level G (DLG) as the recommended phase 3 dose (RP3D).
Aims:
To report updated efficacy and safety of EDR at the RP3D in patients with NDMM.
Materials and Methods/Case Presentation/Objective:
Methods:
Eligible patients had TI (age ≥65 or 65 years with comorbidities impacting the possibility of transplant) NDMM, ECOG PS ≤2, and adequate liver, renal, and bone marrow function. Patients received subcutaneous elranatamab priming in cycle [C]0 (12 mg day [D]1, 32 mg D4), 76 mg on D8, then 76 mg every 4 weeks (Q4W) from C1; daratumumab 1800 mg subcutaneously weekly in C1-C2, every 2 weeks in C3-C6, and Q4W thereafter; and oral lenalidomide 25 mg daily on D1-D21 in 28-day cycles. Endpoints included safety and preliminary
Results/Description/Main Outcome Measure(s):
Results:
Forty patients received ≥1 elranatamab dose. At the March 16, 2026 cutoff, median (range) follow-up was 19.1 (1.2-20.9) months; 34 patients remained on treatment. Confirmed investigator-assessed ORR was 97.5% (95% CI, 86.8-99.9), 77.5% achieved ≥CR, 92.5% ≥VGPR. Median (range) time to response was 1.5 (0.3-4.2) months, median time to ≥CR was 8.1 (3.3-18.0) months. MRD negativity (10-5) rate was 100% among MRD-evaluable patients with ≥CR (n=24).
Treatment-emergent adverse events (TEAEs) occurred in all patients (maximum Grade [G]3/4 95.0%), hematological TEAEs in 87.5% (G3/4 85.0%), and infections in 87.5% (G3/4 25.0%). Common TEAEs (any grade >30%) included neutropenia (80.0%, all G3/4), cytokine release syndrome (62.5%, all G1/2), anemia (40.0%, G3/4 20.0%), diarrhea (37.5%, G3/4 7.5%), and pyrexia (35.0%, all G1/2). One case of G2 ICANS was reported. There was one G5 Candida pneumonia in a patient who did not receive prophylactic immunoglobulin replacement. Infections of bacterial, viral, fungal, and unspecified origin were reported in 32.5%,42.5%, 12.5%, and 60.0% of patients, respectively; 92.5% of patients received ≥1 immunoglobulin replacement treatment.
Conclusion(s).:
Summary/Conclusions:
In patients with TI NDMM, EDR at the RP3D demonstrated rapid and deep responses, which deepened with longer follow-up. Manageable safety was consistent with individual component toxicities. These findings support further evaluation of EDR in MagnetisMM-6 Part 2.
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