Comparison of outcomes with elranatamab and real world treatments in the UK for triple class exposed relapsed and refractory multiple myeloma.

Background: Patients with triple class exposed (TCE), relapsed and refractory (RR) multiple myeloma (MM) have limited treatment options and poor prognosis. Elranatamab, a bispecific BCMA-targeted antibody, is an investigational treatment for RRMM with demonstrated efficacy and safety in MagnetisMM-3, a single-arm, multi-centre, phase-2 study. This study aimed to characterise outcomes for real world TCE RRMM patients and to estimate the treatment effect of elranatamab compared to treatments available in routine clinical care for TCE RRMM in the NHS.

Methods: A retrospective, observational, external control arm (ECA) study combining participants from a single arm, multi-centre phase 2 study, MagnetisMM-3, receiving elranatamab to compare patient characteristics and median survival using a comparator cohort of TCE RRMM patients treated with real world regimens in five UK centres between 2015 and 2023. Both naive and adjusted treatment effect estimates for progression free survival (PFS) and overall survival (OS) were obtained using inverse probability of treatment weighted (IPTW) Cox proportional hazards models and differences in restricted mean survival time (dRMST). Quantitative bias analysis was used to assess the robustness of effect estimates to unmeasured confounding.

Results: From a total of 5,535 patients identified with a diagnosis of MM, 81 were identified as eligible for inclusion in the ECA. A total of 13 different regimens were recorded as being initiated from the real world RRMM at index date, the most common regimen was pomalidomide + dexamethasone (48.15%). Clinical outcomes in the ECA were poor (median PFS 3.71 months [95% confidence interval (CI) 2.73-4.73], median OS 11.00 months [8.02-18.10]). In unadjusted analyses the elranatamab cohort had significant improvements in PFS (dRMST 6.95 months [4.08-9.61]) and OS (Hazard Ratio (HR) 0.66 [0.45-0.96]). Adjusted analyses showed similar effects for PFS (dRMST 6.45 [3.05-9.45]) but were equivocal for OS (HR 0.75 [0.46-1.26]).

Conclusion: This study provides recent real world evidence of poor outcomes in TCE RRMM in the UK. PFS was longer among patients who received elranatamab compared with treatments for TCE RRMM in routine UK clinical practice.