Early data from part 1 of the phase 1b MagnetisMM-30 trial (NCT06215118), presented at the 2025 ASH Annual Meeting, show that elranatamab-bcmm (Elrexfio) combined with iberdomide produced high response rates and a safety profile consistent with the known toxicities of each agent in patients with relapsed or refractory multiple myeloma.
At a median follow-up of 7.8 months (range, 0.7–11.3), the combination induced an objective response rate (ORR) of 95.5% (95% CI, 77.2%–99.9%) in 22 evaluable patients, including a complete response (CR) or better rate of 45.5% and a very good partial response (VGPR) or better rate of 77.3%. Responses were rapid, with a median time to response of 1.4 months (range, 0.5–2.7).
By dose cohort, 13 patients received elranatamab 76 mg once weekly plus iberdomide 1.0 mg (DL1; median follow-up 9.4 months) and had an ORR of 92.3% (95% CI, 64.0%–99.8%), a CR or better rate of 46.2% and a VGPR or better rate of 69.2%. Nine patients received elranatamab 76 mg every 2 weeks plus iberdomide 1.0 mg (DL‑1; median follow-up 5.2 months) and achieved an ORR of 100% (95% CI, 66.4%–100.0%), a CR or better rate of 44.4% and a VGPR or better rate of 88.9%.
Efficacy by cytogenetic risk showed an ORR of 100% (n = 11) in standard-risk patients (CR or better 36.4%; VGPR or better 72.7%) and 88.9% (n = 9) in high-risk patients (CR or better 44.4%; VGPR or better 77.8%). Two patients with missing cytogenetic data both achieved CR.
Among 17 evaluable patients, four dose-limiting toxicities (DLTs) were reported: at DL1, grade 3 anorexia and grade 4 neutropenia; at DL‑1, grade 3 febrile neutropenia and grade 4 neutropenia. All patients experienced at least one treatment-emergent adverse event (TEAE); 86.4% had grade 3 or 4 events. The most common TEAEs were neutropenia (77.3%; grade 3/4 72.7%), cytokine release syndrome (CRS) (68.2%; all grade 1–2), fatigue (63.6%), diarrhea (50.0%), headache (45.5%), cough (45.5%) and nausea (40.9%). Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred at grade 1 or 2 in 9.0% of patients. Infections occurred in 40.9% of patients, with two grade 3 events (E. coli gastroenteritis and a skin infection); the most common infections were upper respiratory tract infection (27.3%), Candida (13.6%) and urinary tract infection (9.1%). Granulocyte colony-stimulating factor was administered to 59.1% of patients.
Dose intensity and management issues were notable: relative dose intensity was 78.2% for elranatamab and 74.3% for iberdomide; dose interruptions occurred for both agents in 81.8% of patients and iberdomide dose reductions were required in 54.5%. Investigators reported better relative dose intensity and tolerability with the every‑2‑week elranatamab schedule.
The trial enrolled 22 patients across centers in the United States, Canada and Australia (data cutoff September 19, 2025). Median age was 68 years (range, 46–83); 45.5% were male and 68.2% were White. Disease stage by Revised International Staging System was I in 22.7%, II in 63.6% and III in 4.5%. Baseline features included 40.9% with high‑risk cytogenetics, 18.2% with extramedullary disease, 50% triple‑class refractory disease and 77.3% with prior high‑dose chemotherapy and stem cell transplant. Thirteen patients were treated at DL1 and nine at DL‑1; five patients in the DL1 cohort discontinued treatment (two for adverse events, two for progressive disease and one death not attributed to study treatment).
MagnetisMM-30 is a phase 1b, open‑label, multicenter study with dose‑escalation and dose‑optimization components enrolling adults with multiple myeloma who received 2–4 prior lines of therapy (including at least one immunomodulatory drug and one proteasome inhibitor) and were BCMA‑naive. Patients received standard step‑up dosing of subcutaneous elranatamab per the approved protocol, then combination therapy: DL1 used elranatamab 76 mg weekly plus iberdomide 1.0 mg once daily (days 1–21 of a 28‑day cycle), while DL‑1 used elranatamab 76 mg every 2 weeks with the same iberdomide schedule. The primary endpoint for part 1 was DLTs; key secondary endpoints include safety, ORR, CR rate, time‑to‑event outcomes and minimal residual disease negativity.
The combination was pursued based on complementary mechanisms: elranatamab is an FDA‑authorized BCMA‑directed bispecific T‑cell engager, and iberdomide is an oral CELMoD with enhanced immunomodulatory and T‑cell–activating properties compared with earlier IMiDs, providing a rationale for potential synergy.
The study is ongoing, with part 2 planned to enroll more patients and evaluate additional dose and schedule combinations to optimize the balance of efficacy and tolerability.
Disclosures: Principal investigator Attaya Suvannasankha reports consultancies with Karyopharm, Bristol Myers Squibb, GlaxoSmithKline, Regeneron, Sanofi and Janssen and research funding from Bristol Myers Squibb, Regeneron, GlaxoSmithKline, Pfizer, Janssen and Sutro.
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