Health related quality of life (HRQoL) in patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE RRMM) treated with idecabtagene vicleucel (ide-cel) versus standard regimens: Patient-reported outcomes (PROs) from KarMMa-3 phase 3 randomized controlled trial (RCT).

person Michel Delforge University of Leuven, Leuven, Belgium info_outline Michel Delforge, Krina K. Patel, Laurie Eliason, Devender Dhanda, Ling Shi, Shien Guo, Thomas Marshall, Bertrand Arnulf, Michele Cavo, Ajay K. Nooka, Salomon Manier, Natalie Scott Callander, Sergio Giralt, Hermann Einsele, Sikander Ailawadhi, Mihaela Popa McKiver, Mark Cook, Paula Rodríguez-Otero

Authors person Michel Delforge University of Leuven, Leuven, Belgium info_outline Michel Delforge, Krina K. Patel, Laurie Eliason, Devender Dhanda, Ling Shi, Shien Guo, Thomas Marshall, Bertrand Arnulf, Michele Cavo, Ajay K. Nooka, Salomon Manier, Natalie Scott Callander, Sergio Giralt, Hermann Einsele, Sikander Ailawadhi, Mihaela Popa McKiver, Mark Cook, Paula Rodríguez-Otero Organizations University of Leuven, Leuven, Belgium, MD Anderson Cancer Center, Houston, TX, Bristol Myers Squibb, Princeton, NJ, Evidera, Bethesda, MD, Hôpital Saint-Louis, Paris, France, Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy, Winship Cancer Center of Emory University, Atlanta, GA, Centre Hospitalier Universitaire de Lille, Lille, France, University of Wisconsin Health, Carbone Cancer Center, Madison, WI, Memorial Sloan Kettering Cancer Center, New York, NY, Medizinische Klinik und Poliklinik II, Uniklinikum Würzburg, Würzburg, Germany, Mayo Clinic, Jacksonville, FL, Celgene International Sàrl, a Bristol-Myers Squibb Company, Boudry, Switzerland, Clínica Universidad de Navarra, Pamplona, Spain Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Bristol Myers Squibb Background: Patients (pts) with TCE RRMM have few treatment (Tx) options and poor HRQoL. Ide-cel, the first in class CAR T cell Tx for pts with TCE RRMM, improved PFS versus standard (std) regimens in the KarMMa-3 trial. We report the PRO results comparing the Tx arms. PROs provide further understanding of Tx benefit of ide-cel from the pts’ perspective. Methods: KarMMa-3 (NCT03651128) is an open-label phase 3 RCT comparing the efficacy and safety of ide-cel with std regimens in pts with TCE RRMM, who had received 2–4 prior regimens. In addition to clinical endpoints, we evaluated the impact of ide-cel compared with std regimens on the changes in HRQoL, measured by the EORTC QLQ-C30, EORTC QLQ-MY20, and the EQ-5D-5L questionnaires. PROs were collected at baseline (screening), day of infusion and monthly from 2–24 months (mo) and thereafter every 3 mo. This interim analysis reports PROs through 20 mo. Comparisons were performed on least squares mean (LSM) changes from baseline over time between arms using constrained longitudinal data analysis (cLDA). Results: In total, 386 pts 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 mo showed significant differences ( P < 0.05), with effect sizes of 0.3–0.7, in favor of ide-cel for most domains, including global health status/QoL, cognitive functioning, fatigue, and pain (EORTC QLQ-C30); side effects of Tx (EORTC QLQ-MY20); and the EQ-5D-5L VAS. The difference in overall LSM change reached or exceeded the pre-specified between-groups minimal importance difference (MID) for improvement in most domains in favor of ide-cel (Table). Conclusions: Ide-cel showed statistically significant and clinically meaningful improvements in HRQoL, including key MM symptoms and functioning, for pts with TCE RRMM compared with std regimens. The PRO data for ide-cel expands upon the clinical outcomes observed in the KarMMa-3 trial. Clinical trial information: NCT03651128. Differences in cLDA overall LSM changes from baseline to 20 mo in ide-cel versus std regimen arm. Instrument/Domain Diff Between Arms LSM (95% CI) Ide-cel versus Std Regimens MID Hedges’ g (95% CI) EORTC QLQ-C30 Global health status/QoL 6.17* (3.35, 8.99) 4 0.46 (0.25, 0.68) Physical functioning 4.32* (1.66, 6.98) 5 0.34 (0.13, 0.56) Cognitive functioning 5.64* (3.02, 8.27) 3 0.46 (0.24, 0.67) Fatigue −6.24* (−9.52, −2.96) −5 −0.40 (−0.62, −0.19) Pain −5.68* (−9.36, −1.99) −6 −0.33 (−0.54, −0.11) EORTC QLQ-MY20 Side effects of Tx −6.08* (−7.89, −4.26) −10 −0.71 (−0.93, −0.49) EQ- 5D-5L VAS 7.26* (4.70, 9.83) 7 0.60 (0.39, 0.82) * P value < 0.05.; Results favor ide-cel with - values for symptoms (fatigue, pain) and side effects and + values for functioning/health.

Clinical