Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial

Abstract

Multiple myeloma (MM) is a plasma cell malignancy expressing B cell maturation antigen (BCMA). Elranatamab, a bispecific antibody, engages BCMA on MM and CD3 on T cells. The MagnetisMM-1 trial evaluated its safety, pharmacokinetics and efficacy. Primary endpoints, including the incidence of dose-limiting toxicities as well as objective response rate (ORR) and duration of response (DOR), were met. Secondary efficacy endpoints included progression-free survival (PFS) and overall survival (OS). Eighty-eight patients with relapsed or refractory MM received elranatamab monotherapy, and 55 patients received elranatamab at efficacious doses. Patients had received a median of five prior regimens; 90.9% were triple-class refractory, 29.1% had high cytogenetic risk and 23.6% received prior BCMA-directed therapy. No dose-limiting toxicities were observed during dose escalation. Adverse events included cytopenias and cytokine release syndrome. Exposure was dose proportional. With a median follow-up of 12.0 months, the ORR was 63.6% and 38.2% of patients achieving complete response or better. For responders, the median DOR was 17.1 months. All 13 patients evaluable for minimal residual disease achieved negativity. Even after prior BCMA-directed therapy, 53.8% achieved response. For all 55 patients, median PFS was 11.8 months, and median OS was 21.2 months. Elranatamab achieved durable responses, manageable safety and promising survival for patients with MM. ClinicalTrials.gov Identifier: NCT03269136 .

Fig. 1

CONSORT diagram of MagnetisMM-1.

Fig. 2. Elranatamab pharmacokinetics.

A priming dose was not administered during dose escalation (part 1), whereas a single priming dose of 600 µg kg⁻¹ (or equivalent 44-mg fixed dose) was administered 1 week before the RP2D during expansions (part 1.1 and part 2A). C, cycle; D, day.

Fig. 3. Best overall response and duration of treatment.

Swimmer plot depicts disease assessments relevant to first response, confirmation of response, deepening of response and best response. Black asterisk indicates prior anti-BCMA ADC. Blue asterisk indicates prior BCMA-targeted CAR-T. MR, minimal response; NE, not evaluable; PD, progressive disease; REL, relapse; SD, stable disease.

Fig. 4. Kaplan–Meier plot.

a–c, Kaplan–Meier plot. for DOR (a), PFS (b) and OS (c). NE, not estimable.

Fig. 5. Duration of treatment and molecular response for patients achieving CR or sCR.

MRD status was assessed by next-generation sequencing at a sensitivity of 1 × 10⁻⁵ in accordance with IMWG criteria. Evaluable patients had a dominant VDJ or VJ sequence at baseline and confirmed response of CR or better. Black asterisk indicates ‘not evaluable’. u, unconfirmed.

Extended Data Fig. 1. Effect of premedication on cytokine production including (a) IFN-γ, (b) TNF-α, (c) IL-2, and (d) IL-6.

The mean is plotted from 20 patients in Part 1.1 and 15 patients in Part 2A. Error bars represent standard error of the mean. C, cycle; D, day; H, hour; IFN-γ, interferon-gamma; IL-2, interleukin 2; IL-6, interleukin 6; TNF-α, tumor necrosis factor-alpha.

Extended Data Fig. 2. Elranatamab-induced changes in soluble BCMA.

BCMA, B-cell maturation antigen; CR, complete response; MR, minimal response; PD, progressive disease; PR, partial response; QW, once weekly; sBCMA, soluble B-cell maturation antigen; sCR, stringent complete response; SD, stable disease; VGPR, very good partial response.

Extended Data Fig. 3. Objective response rate across subgroups. Square denotes ORR and the whiskers indicate 95% CI (Clopper-Pearson).

Liver function: normal = AST and total bilirubin ≤ULN; impaired = AST or total bilirubin >ULN (including both AST and total bilirubin >ULN). AST, aspartate aminotransferase; BCMA, B-cell maturation antigen; CI, confidence interval; CrCl, creatinine clearance; ECOG PS, Eastern Cooperative Oncology Group performance status; ORR, objective response rate; ULN, upper limit of normal.