Secondary Quality-of-Life Domains in Patients with Relapsed and Refractory Multiple Myeloma Treated with the Bcma-Directed CAR T Cell Therapy Idecabtagene Vicleucel (ide-cel; bb2121): Results from the Karmma Clinical Trial
Authors: Shah Nina , Delforge Michel , San-Miguel Jesús F. , Bertin Kaitlyn B. , Tahir Muna J , Lewis Hannah B. , Wang Julie , Braverman Julia , Campbell Timothy B. , Dhanda Devender , Munshi Nikhil C. 
Published: November 2020

Introduction: Patients with relapsed and refractory multiple myeloma (RRMM) have limited treatment options and experience poor health-related quality of life (HRQoL). Ide-cel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell therapy, has shown a favorable clinical benefit-risk profile in patients with RRMM in the phase 2, single-arm KarMMa trial (Munshi NC, et al. J Clin Oncol 2020;38:8503). The impact of ide-cel treatment on primary HRQoL domains of interest preselected as most relevant for the treatment and target population (Fatigue, Pain, Cognitive Functioning, Physical Functioning, and Global Health) has been recently described (Delforge M, et al. HemaSphere 2020;4:EP1000). The aim of this analysis was to report the impact of ide-cel treatment on secondary HRQoL domains of interest and health utility scores in patients with RRMM in the KarMMa trial.
Methods: Patients enrolled in the KarMMa trial (NCT03361748) had ≥ 3 prior antimyeloma treatment regimens (including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody) and were refractory to their last regimen per International Myeloma Working Group criteria. After lymphodepletion, patients received ide-cel at target dose levels of 150, 300 and 450 × 106 CAR+ T cells. HRQoL was assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life C30 (QLQ-C30) and Myeloma Module (MY20) questionnaires and the EuroQol 5 dimensions 5 levels (EQ-5D-5L) instrument at screening, baseline, on the day of ide-cel infusion, and throughout the follow-up period at Months 1-6, 9, 12, and 15 post-infusion. For each domain, clinically meaningful changes from baseline were predefined as recommended in the literature. Analyses were performed after the cutoff date, October 16, 2019, and included patients with ≥ 9+1 months of follow-up. Statistical significance was calculated using the 2-sided Wilcoxon signed-rank test (0.05 significance level). EQ-5D-5L utility indices were calculated using the UK value set as the reference country and compared with UK general population data.
Results: Of 128/140 patients enrolled in the KarMMa trial who received ide-cel, 95% (EORTC QLQ-C30) and 94% (EORTC QLQ-MY20, EQ-5D-5L) had a baseline and ≥ 1 post-baseline HRQoL assessment and were evaluable for HRQoL. The compliance rate was ≥ 80% for most visits. For EORTC QLQ-C30, patients demonstrated a clinically meaningful improvement in most functioning and symptom subscale scores from baseline to Month 3 through 15, with statistical significance (p &lt; 0.05) reached at various time points for different subscales throughout the follow-up period. For the Role Functioning, Emotional Functioning and Social Functioning subscales, &gt; 40% of patients reported a clinically meaningful improvement from baseline, ~25% had deterioration and ~35% had no change from baseline from Month 2 onward (Figure shows Month 9 results). Stable status was most frequently observed (~60%) on the Nausea/Vomiting, Constipation, Diarrhea, Insomnia, Dyspnea and Appetite Loss, and Financial Difficulties subscales.
For EORTC QLQ-MY20, the mean change from baseline on the Future Perspectives subscale demonstrated a clinically meaningful improvement from baseline at Month 2 through 15, with statistical significance (p &lt; 0.05) reached at Month 5. Body Image subscale scores remained stable from baseline through Month 15. The greatest proportion of patients (&gt; 48%) experienced a clinically meaningful improvement from baseline on the Future Perspective subscale. Stable status was most frequently observed (&gt; 59%) for the Body Image subscale.
Both EQ-5D-5L index (0.68 vs 0.86) and EQ visual analogue scale (EQ VAS) scores (68 vs 83) were lower for patients treated with ide-cel when compared with UK general population scores. The index and EQ-VAS mean scores became more comparable to the UK data over time, showing a clinically meaningful (although not statistically significant) improvement from baseline beginning at Month 2 (EQ-5D-5L) or 3 (EQ-VAS) through Month 15. In most patients, a clinically meaningful improvement from baseline was observed, increasing from ~43% to ~47% (EQ-5D-5L index score) and ~57% to ~68% (EQ-VAS).
Conclusion: These results show that ide-cel treatment brings clinically meaningful quality-of-life benefits to triple-class-exposed patients with RRMM without compromising any HRQoL domains.

Disclosures
Shah: BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding; GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy. Delforge:Amgen: Honoraria; BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bertin:ICON plc: Current Employment. Tahir:ICON plc: Current Employment. Lewis:ICON plc: Current Employment. Wang:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Braverman:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Campbell:BMS: Current Employment, Current equity holder in publicly-traded company. Dhanda:BMS: Current Employment, Current equity holder in publicly-traded company. Munshi:Takeda: Consultancy; C4: Current equity holder in private company; Janssen: Consultancy; Adaptive: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy.