Updated Health-Related Quality of Life Results from the KarMMa Clinical Study in Patients with Relapsed and Refractory Multiple Myeloma Treated with the B-Cell Maturation Antigen-Directed Chimeric Antigen Receptor T Cell Therapy Idecabtagene Vicleucel (ide-cel, bb2121)
Authors: Delforge Michel , Shah Nina , Rodríguez-Otero Paula , Braverman Julia , Dhanda Devender , Shi Ling , Guo Shien , Yu Peiwen , Liao Weiqin , Campbell Timothy B. , Munshi Nikhil C. 
Published: November 2021

Abstract
Introduction: Patients with heavily pretreated relapsed and refractory multiple myeloma (RRMM) have poor outcomes and poor health-related quality of life (HRQoL). The B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy ide-cel has shown frequent, deep, and durable responses in patients with RRMM who were triple-class exposed (TCE) to immunomodulatory drugs, proteasome inhibitors (PI), and anti-CD38 monoclonal antibodies in the pivotal, phase 2, single-arm KarMMa trial (Munshi NC, et al. N Engl J Med 2021;384:705-716). Ide-cel is approved in the US by the FDA for the treatment of adults with RRMM after ≥ 4 prior lines of therapy, including an immunomodulatory drug, PI, and anti-CD38 monoclonal antibody. We have shown previously that in the KarMMa trial, ide-cel provides clinically meaningful benefits in HRQoL at 9 months' follow-up (Delforge M, et al. HemaSphere 2020;4(suppl 1). Abstract EP1000; Shah N, et al. Blood 2020;136(suppl 1):28-29). The aim of this analysis was to extend previous reports by analyzing the effect of ide-cel on HRQoL at 24 months post-infusion data cut off (December 21, 2020) in patients with TCE RRMM in the KarMMa trial.
Methods: In the KarMMa trial (NCT03361748), eligible patients had ≥ 3 prior antimyeloma treatment regimens, were TCE, and refractory to their last treatment regimen per International Myeloma Working Group criteria. To assess HRQoL, European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 (QLQ-C30), EORTC QLQ Multiple Myeloma Module (QLQ-MY20) and EuroQoL 5 dimensions 5 levels (EQ-5D-5L) questionnaires were administered at screening, baseline, at ide-cel infusion, at months 1-6, and every 3-6 months up to month 24 or end of study. Thresholds for clinically meaningful changes from baseline were predefined. Statistical significance was calculated using the 2-sided Wilcoxon signed rank test (0.05 significance level).
Results: Of 128 patients treated with ide-cel, 126 (98%) had a baseline and ≥ 1 post-baseline HRQoL assessment and were included in the HRQoL-evaluable population. The patient questionnaire completion rate was ≥ 75% up to month 6 and 50%-70% thereafter for most visits.
For the predefined primary HRQoL domains, mean scores improved after ide-cel treatment and were comparable to the general population (Table). Mean changes from baseline exceeded the minimal important difference (MID) threshold for clinically meaningful improvement in fatigue, pain, physical functioning, cognitive functioning, and global health status/quality of life (QoL) scores of QLQ-C30 and disease symptom scores of QLQ-MY20 through month 24 (data cutoff, December 21, 2020). Side effects of treatment (QLQ-MY20) remained stable. Overall, 40%-70% of patients had clinically meaningful improvements in the QLQ-C30 fatigue, pain, physical functioning, and global health status/QoL scores at later timepoints. Moreover, 30%-40% of patients experienced clinically meaningful improvements in cognitive functioning, disease symptoms, and side effects, with 40%-60% of patients remaining stable in these domains, across most of the post-baseline assessment visits.
Predefined secondary HRQoL domains included all other domains from QLQ-C30 and -MY20, EQ-5D-5L health utility index scores, and EQ-5D visual analogue scale (VAS) scores. Mean changes from baseline exceeded the MID thresholds for clinically meaningful improvement and reached statistical significance across most follow-up visits for role functioning, emotional functioning, social functioning, dyspnea, insomnia, constipation, diarrhea (QLQ-C30), future perspectives (QLQ-MY20), health utility index scores (EQ-5D-5L), and VAS scores (EQ-5D). Mean changes from baseline for nausea/vomiting, appetite loss, financial difficulties (QLQ-C30), and body image (QLQ-MY20) scores were not clinically meaningful. At the individual level, most patients remained stable or achieved clinically meaningful improvements in secondary domains of interest across almost all follow-up visits.
Conclusion: In this study, patients with TCE RRMM who received a single infusion of ide-cel showed clinically meaningful improvements across multiple HRQoL domains during the 24-month follow-up period.
Figure 1 Figure 1.

Disclosures
Delforge: Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah: Sanofi: Consultancy; Sutro Biopharma: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Kite: Consultancy; Indapta Therapeutics: Consultancy; Poseida: Research Funding; Nektar: Research Funding; Precision Biosciences: Research Funding; Karyopharm: Consultancy; GSK: Consultancy; CareDx: Consultancy; BMS/Celgene: Research Funding; Bluebird Bio: Research Funding; CSL Behring: Consultancy; Amgen: Consultancy; Teneobio: Research Funding. Rodríguez-Otero: Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy; Janssen, Celgene, Amgen, Oncopeptides, Sanofi, Abbvie, GlaxoSmithKline, Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Regeneron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Braverman: BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda: BMS: Current Employment, Current equity holder in publicly-traded company. Shi: Bristol Myers Squibb: Consultancy. Guo: Bristol Myers Squibb: Consultancy; Daiichi Sankyo: Consultancy; UCB: Consultancy; Janssen: Consultancy; Gilead: Consultancy; EMD Serono: Consultancy; Evidera: Current Employment. Yu: Evidera: Current Employment. Liao: Evidera: Current Employment. Campbell: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company. Munshi: Legend: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Abbvie: Consultancy; Pfizer: Consultancy; Adaptive Biotechnology: Consultancy; Novartis: Consultancy; Oncopep: Consultancy, Current equity holder in publicly-traded company, Other: scientific founder, Patents & Royalties; Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy.