Elranatamab for relapsed/refractory multiple myeloma – multi-centre real-world outcomes from the United Kingdom
Year: 2025
Type: conference-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.
Source: Blood
Authors: Oliver Tomkins, Hannah Giles, Guy Pratt, Bhuvan Kishore, Frances Seymour, Kanta Devi, Charles Agbuduwe, Fatema Alnashaba, Thomas Creasey, Eleanor Ziegler, Pablo Tenorio Feixas, Katharine Bailey, Dean Smith, Ellen Gokkel, Karthik Ramasamy, Ceri Bygrave, Grant Mehrjou, Matthew Jenner, Annisa Butt, Andrew King, Dunnya De-Silva, Fenella Willis, Shelina Sachedina, Clemens Ziller, Jindriska Lindsay, Kenna Robertson, Hugues de Lavallade, Sajitha Sachchithanantham, Neeraj Kohli, Majid Kazmi, Matthew Streetly, Dana Warcel
Institutions: Guy's and St Thomas' NHS Foundation Trust, University Hospitals Birmingham NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust, Imperial College Healthcare NHS Trust, Newcastle upon Tyne Hospitals NHS Foundation Trust, King's College Hospital NHS Foundation Trust, King's College Hospital, Nottingham University Hospitals NHS Trust, Oxford University Hospitals NHS Trust, University Hospital Southampton NHS Foundation Trust, Cambridge University Hospitals NHS Foundation Trust, Maidstone and Tunbridge Wells NHS Trust, St George’s University Hospitals NHS Foundation Trust, University Hospitals of Leicester NHS Trust
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W7108453969