Abstract

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM.

Highlights

  • Multiple myeloma is the second most common hematologic malignancy, with ~160,000 newly diagnosed cases and 106,000 deaths worldwide in 2018 [1]

  • This improvement has been primarily driven by more effective combination therapies of immunomodulatory agents, proteasome inhibitors (PIs), and dexamethasone coupled with consolidation using autologous stem cell transplant [3, 5]

  • Patients Patient-level data were collected from 1949 real-world patients with refractory multiple myeloma (RRMM) who received ≥3 prior regimens, including an immunomodulatory agent, a PI, and an anti-CD38 antibody

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Summary

Introduction

Multiple myeloma is the second most common hematologic malignancy, with ~160,000 newly diagnosed cases and 106,000 deaths worldwide in 2018 [1]. Previous retrospective data for patients with multiple myeloma refractory to immunomodulatory agents, PIs, and anti-CD38 monoclonal antibodies from 14 different US academic institutions reported a median progression-free survival (PFS) of only 3−4 months and a median OS of 8−9 months [16]. Such triple-class exposed patients with relapsed and refractory multiple myeloma (RRMM) have few treatment options, even with the newly approved therapy belantamab mafodotin [17, 18], and there is no clear consensus on the optimal therapy or standard of care [16, 18,19,20,21,22]

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