Matching-Adjusted Indirect Comparisons of Efficacy Outcomes in Patients with Relapsed and Refractory Multiple Myeloma for Idecabtagene Vicleucel (KarMMa) Versus Selinexor Plus Dexamethasone (STORM Part 2) and Belantamab Mafodontin (DREAMM-2): Updated Analysis with Longer Follow-up

Introduction: Idecabtagene vicleucel (ide-cel, bb2121) is a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy approved in the US by the Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, i.e. triple-class exposed (TCE). Selinexor plus dexamethasone (Sd) and belantamab mafodotin (BM) are 2 other FDA-approved regimens for similarly heavily pretreated patients, including those who are TCE. All 3 interventions were evaluated in phase 2 single-arm clinical trials: KarMMa (ide-cel), STORM Part 2 (Sd), and DREAMM-2 (BM). Previously, efficacy outcomes were compared between ide-cel (median follow-up: 13.3 months) and Sd (median follow-up: not reported [NR]) or BM (median follow-up: 6.3 months) using unanchored matching-adjusted indirect comparisons (MAICs) (Rodríguez-Otero P, et al. HemaSphere 2020;4(Suppl 2). Abstract EP969.). The current analysis updates the MAICs using longer follow-up data for ide-cel (median: 19.9 months) and BM (median: 9.0 months). Methods: Between-study differences in patient characteristics were adjusted using individual-level patient data (IPD) from KarMMa and aggregate-level data from either STORM Part 2 or DREAMM-2. The populations of interest included the population treated with ide-cel (N = 128) from KarMMa (of whom 54 patients received the 450 × 10 6 CAR+ T cell target dose), the modified intention-to-treat (ITT) population from STORM Part 2 (N = 122), and the ITT population for the 2.5 mg/kg dose of BM from DREAMM-2 (N = 97). A weighted logistic regression was performed to calculate odds ratios (ORs) for binary outcomes and a weighed Cox regression was performed to calculate hazard ratios (HRs) for time-to-event outcomes. Outcomes of interest included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A Kaplan-Meier curve for DOR was NR in STORM Part 2; therefore, the DOR comparison was restricted to DREAMM-2. Selection of covariates for the propensity model was informed by a literature review that identified prognostic factors included in published indirect treatment comparisons involving RRMM trials, a previous analysis comparing the KarMMa patient cohort treated with ide-cel to a real-world cohort, and clinical consu