Elranatamab for relapsed/refractory multiple myeloma – multi-centre real-world outcomes from the United Kingdom

Abstract

Abstract Background Elranatamab is a humanised B-cell maturation antigen (BCMA)-CD3 bispecific antibody. It is available in England and Wales under a managed access scheme for relapsed or refractory (R/R) multiple myeloma (MM) patients following ≥3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody. The phase 2 MagnetisMM-3 (MM-3) study reported an overall response rate (ORR) of 61% with 37.4% complete response (CR). At median follow-up of 33.9 months (m), median progression-free survival (PFS) was 17.2m and median overall survival (OS) 24.6m. We report real world outcomes of elranatamab treated patients across 15 United Kingdom sites. Methods We undertook a multicentre, retrospective chart-review of patients who received ≥1 dose of elranatamab at participating sites. Anonymised patient data collection was carried out under institutional approvals. Response assessment was performed according to IMWG criteria. Treatment-emergent adverse events (TEAEs) were graded according to NCI CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) as per ASTCT criteria. Kaplan-Meier estimate was used to calculate OS, PFS and duration of response (DOR), with reverse method for follow-up. Results 195 patients received elranatamab between April 2024 and July 2025 with a median follow-up of 8.1m. Median age was 66 years (IQR 59-74 years); 61% were male and 15% were non-Caucasian. At baseline, 25% had ECOG performance status (PS) of 2, 36% had high risk cytogenetics, defined as del(17p), gain(1q), t(14;20), t(14:16) or t(4:14), 22% had ISS stage III disease and 19% had extramedullary disease. Patients had received a median of four (IQR 3-5) prior lines of therapy; 75% were triple-class refractory, 31% were penta-class refractory and 15% were BCMA-exposed. Best response was evaluable in 172/195 patients with an ORR of 71%; 27% complete response (CR), 28% very good partial response (VGPR) and 14% partial response (PR). Time to first response and best response were 28 and 75 days, respectively. Median DOR was not reached (NR), with 12-m DOR rate of 59%. Estimated median OS was 18.3m (18.3-NR), with a 12-m OS rate of 68%. Estimated median PFS was 11.8m (95% CI: 6.5-14.2m) with 6- and 12-m PFS rates of 60.7% and 50% respectively. Patients in ≥VGPR had a 12-m OS and PFS of 88% and 75% respectively. On univariable analysis, PFS was affected by prior anti-BCMA exposure (p=0.006, median 4.7 vs 15.1m), but not high-risk cytogenetics (p=0.9). 53% of patients had discontinued elranatamab: 33% due to progressive disease and 13% TEAEs. 54% had CRS, all ≤grade 2 events; 64% received tocilizumab. 6% had ICANS including six grade 2 and three grade 3 events, with dexamethasone administered in 4%. Confirmed or suspected bacterial infections occurred in 36%, with 25% ≥grade 3. Viral infections occurred in 36%, with 14% ≥grade 3 including two confirmed cases of progressive multifocal leukoencephalopathy (PML). 51% received immunoglobulin replacement at a median of 3 months into treatment. Anaemia, neutropenia and thrombocytopenia occurred in 64%, 63% and 53% of patients respectively. Discussion In this real-world cohort of 195 patients, elranatamab resulted in an ORR of 71% with an estimated median PFS and estimated median OS of 11.8 and 18.3m respectively. The median follow-up duration of 8.1m is short, but preliminary results show promising trends. Compared to the pivotal MM3 trial, ORR is higher but PFS and OS are shorter. There was a higher proportion of frail patients with high risk and advanced disease, including 15% with prior anti-BCMA exposure, 25% ECOG PS 2, 36% high-risk cytogenetics and 19% had ISS stage III disease. Patients achieving ≥VGPR showed favourable outcomes, with superior OS and PFS. The most common reasons for treatment discontinuation were progressive disease in 33% and TEAEs in 13%, again similar to MM3. CRS rates were comparable to MM3, but incidence of ICANS higher at 6% vs 3%. All grade and ≥3 grade infections were favourable at 53% and 32%, respectively, compared to 70% and 40% in MM3. However, the two cases of PML are relevant, highlighting the potential impact of profound immunosuppressive therapy and the increased susceptibility to viral pathogens. Despite short follow-up, this real-world data set shows that elranatamab has good efficacy, and is associated with favourable outcomes in a heavily pre-treated R/R MM cohort.