Patient reported outcomes in Triple Class Exposed, Relapsed/Refractory Multiple Myeloma (TCE RRMM) patients in KarMMa 3 trial (Phase 3 RCT): idecabtagene Vicleucel (ide-cel) versus standard regimens

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) have few treatment options and poor health-related quality of life (HRQoL). Ide-cel, the first-in-class chimeric antigen receptor (CAR) T cell therapy for patients with TCE RRMM, improved progression-free survival versus standard (std) regimens in the KarMMa-3 trial. We report patient-reported outcome (PRO) results comparing the 2 treatment arms. PROs provide further understanding of treatment benefit of ide-cel from the patients’ perspective. Aims: To compare PRO results in patients treated with ide-cel versus std regimens, including overall changes over time, and time to confirmed improvement or deterioration various aspects of HRQoL. Methods: KarMMa-3 (NCT03651128) is an open-label, phase 3 randomized controlled trial (RCT) comparing the efficacy and safety of ide-cel with std regimens in patients with TCE RRMM who received 2–4 prior regimens (Rodriguez-Otero P, et al. N Engl J Med 2023;384:705–716). In addition to clinical endpoints, we evaluated the impact of ide-cel compared with std regimens on changes in HRQoL as secondary endpoints using the EORTC QLQ-C30, EORTC QLQ-MY20, and EQ-5D-5L questionnaires. PROs were collected at baseline (screening), day of infusion, and monthly from 2 to 24 months and thereafter every 3 months. Comparisons were performed on least squares mean (LSM) changes from baseline over time between arms using constrained longitudinal data analysis (cLDA). Time to confirmed improvement and deterioration, defined based on prespecified change thresholds, was compared between arms using the stratified Cox regression analysis. Results: In total, 386 patients were randomized (ide-cel, 254; std regimens, 132). PRO compliance was high over time (>80%). At baseline, PROs were similar between arms. LSM changes from baseline to 20 months showed significant differences (P <0.05) with effect sizes of 0.3–0.7 (Hedges’ g) in favor of ide-cel for most domains, including global health status/quality of life (QoL), cognitive functioning, fatigue, and pain (EORTC QLQ-C30); side effects of treatment (EORTC QLQ-MY20); and the EQ visual analogue scale (EQ-VAS). The difference in overall LSM change reached or exceeded the prespecified between-groups minimal importance difference (MID) for improvement in most domains in favor of ide-cel. Time to confirmed improvement was significantly shorter (P <0.05) in the ide-cel arm for the majority of EORTC QLQ-C30 and QLQ-MY20 domains and the EQ-VAS. Time to deterioration was numerically longer for ide-cel for almost all domains, with significant differences for QLQ-C30 emotional functioning, cognitive functioning, dyspnea, insomnia, and constipation, and the QLQ-MY20 side effects of treatment (Table). Summary/Conclusion: Ide-cel showed statistically significant and clinically meaningful improvements in HRQoL, including domains related to key MM symptoms and functioning for patients with TCE RRMM compared with std regimens. Ide-cel-treated patients also experienced faster improvements and delayed worsening in many domains. These PRO findings for ide-cel expands upon the clinical outcomes observed in the KarMMa-3 trial.© 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved. Keywords: Quality of life, Multiple myeloma, CAR-T, B-cell maturation antigen