Introduction Elranatamab (ELRA) is a humanized, bispecific antibody that targets both B-cell maturation antigen (BCMA) on multiple myeloma (MM) cells and CD3 on T cells, with the aim of inducing T cell–mediated cytolysis of the MM cells. ELRA was approved in the US and EU in 2023 as monotherapy for the treatment of triple-class exposed relapsed-refractory MM based on the phase II MagnetisMM-3 (NCT04649359) registrational study. ELRA started with 2 step-up priming doses (SUD): 12 mg on day 1 and 32 mg on day 4 of cycle 1 followed by the initial 76 mg dose. The aim here is to report ELRA SUD patterns and related CRS and ICANS in the real-world settings.

Methods AMbreLA (EUPAS1000000074) is an observational ambispective study to evaluate the effectiveness and safety of ELRA in the real-world setting in adult patients who initiated ELRA in France from May 2023 to September 2025, as part of the early access program. Only retrospective and ambispective patients (no prospective-only patients) were selected for this first interim analysis to ensure a longer follow-up period. Adverse events (AEs) occurring prior to patient inclusion are collected only if they are related to a Pfizer product, while AEs occurring after inclusion are collected regardless of whether they are related to a Pfizer product. The results presented here are part of the first interim analysis with a data cut-off of February 28, 2025, and will be updated with data cut-off planned on July 31, 2025. We descriptively analyzed patient and disease characteristics, prior line(s) of therapy, SUD patterns, incidence of CRS and ICANS and overall response rate (ORR).

ResultsThese results will be updated for the poster presentation to include approximately 80 patients from 31 medical centers A total of 28 patients from 13 centers who received ELRA between June 29, 2023, and December 23, 2024, were included in this analysis. The median (95% CI) follow-up was 9.9 (6.1-13.9) months.

Median (Q1-Q3) age was 71.5 (66.5-74.5) years; 25% were aged ≥75 years. 57.1% were male. Median time from first MM diagnosis to ELRA initiation was 9.2 (4.6-12.3) years. 60.7% of patients had at least one comorbidity at ELRA initiation, 35.7% had hypertension, 21.4% had renal impairment/failure, and 10.7% had peripheral neuropathy. 37.5% of patients had an ECOG-PS ≥2 and 68.4% had an ISS of II or III. 35.7% had extramedullary disease and, among patients with genetic screening available (n=17/28), 3 (17.6 %) harbored del(17p). Patients received a median of 5 (range, 2-12) prior lines of therapy. 96.4% were triple-class exposed, 67.9% were penta-class exposed, and 6 (21.4%) had received prior BCMA-directed therapy, of whom 5 had received CAR-T cell therapy and 1 had received both an antibody-drug conjugate and a BCMA bispecific. 23.3% of the patients received ELRA in out-patient hospitalization setting, during or after the SUD schedule, the others were treated in conventional hospitalization.

All patients completed SUD schedule except for 1 who progressed after the second dose. Median time from SUD 1 to 2, 2 to 3 and 1 to 3 was 3.0 (3.0-4.0), 4.0 (3.0-4.5) and 7.0 (7.0-8.0) days, respectively. 67.9% of patients started the full dose (76 mg) on or before day 8. 28 (100%) patients received per-label recommended pre-medication.

CRS was observed in 46.4% of patients, and no serious CRS was reported, whereas 2 ICANS were reported in 1 patient (including 1 SAE). CRS occurred after doses 1 (71.4%), 2 (21.4%), and 3 (7.1%). Recurrent CRS and ICANS occurred in 1 patient. Median time to onset of CRS and ICANS was 3.0 (2.0-3.8) and 11.5 (6.8-16.2) days, respectively. Median time to resolution of CRS and ICANS was 2.5 (2.0-4.0) and 8.0 (8.0-8.0) days, respectively. No patient permanently discontinued ELRA treatment due to CRS or ICANS.

Overall, 21 (75%) patients experienced at least 1 AE including 6 (21.4%) who had at least 1 SAE. 5 (17.9%) patients had an AE leading to treatment discontinuation. ORR was reached by 17 patients. VGPR or better was achieved by 16 patients. Median time to VGPR or better was 1.9 (0.9-4.2) months.

Conclusions These preliminary results of the AMbreLA study provide an accurate picture of real-world SUD patterns. It confirms that the adapted ELRA SUD schedule and per-label recommended premedication is associated with good management of CRS and ICANS. More patients with longer follow-up are needed to update these data, as real-world profiles and treatment patterns may evolve over time.

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2025
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