Meaningful Change in Patient-Reported Outcomes after CAR T-Cell Therapy for Relapsed/Refractory Multiple Myeloma in Standard of Care: Differences By Race and Ethnicity

Background: Chimeric antigen receptor T-cell therapies (CAR Ts) have revolutionized treatment of relapsed/refractory multiple myeloma (RRMM), with remarkable improvements in progression free and overall survival in both clinical trials and standard of care settings. Clinical trials also show meaningful improvements in patient-reported outcomes (PROs) such as health-related quality of life (HRQOL) and patient-reported symptom burden, but PROs from RRMM patients treated in standard of care are limited. Moreover, racial and ethnic minority patients are underrepresented in key RRMM CAR T clinical trials, despite RRMM disproportionately affecting non-Hispanic Black (NHB) individuals compared to non-Hispanic White individuals (NHW). To address this gap, we assessed meaningful changes in PROs after CAR T and explored differences by race/ethnicity in a cohort of RRMM patients treated with CAR T in standard of care. We hypothesized that the majority of patients would show stable or meaningfully improved PROs from pre-CAR T to day 90 post-infusion.

Methods: Patients with RRMM scheduled to receive CAR T as standard of care at Moffitt Cancer Center were recruited between September 2022 and June 2024. PROs were assessed at baseline (pre-lymphodepleting chemotherapy) and day 90 post-CAR T. Participants completed the Functional Assessment of Cancer Therapy - General (FACT-G), which assesses overall HRQOL as well as physical, social, emotional, and functional well-being. Minimally important differences (MIDs) were defined as a ±4-point change for overall HRQOL and ±2-point change for all other FACT-G domains. Participants also completed PRO Measurement Information System (PROMIS) measures of depression, anxiety, fatigue, sleep disturbance, pain interference, global pain, physical function, cognitive function, and social function. MIDs were defined as a ±2-point change for global pain and ±5 for all other PROMIS measures. For each participant, MIDs were used to determine whether changes from baseline to day 90 were clinically meaningful (i.e., meaningful improvement, stable/no meaningful change, or meaningful deterioration). Chi-square analyses and Fisher's exact tests were used to compare differences between racial/ethnic groups.

Results: Participants (N=99) were treated with idecabtagene-vicleucel (n=49) and ciltacabtagene-autoleucel (n=50). Most participants were male (61%), and median age was 66 years (range 46-84). Most self-identified as NHW (68%), followed by NHB (16%), Hispanic (15%), and other (1%). Racial/ethnic minority participants (32%) were less likely than NHW participants to be retired (50% vs. 67%) and more likely to be working (31% vs. 9%; p=0.019). There were no other differences in demographics and no differences in PROs between NHW and racial/ethnic minority participants at baseline (p-values>0.05). Across all PROs, most participants reported meaningful improvement (16-48%) or stable/no meaningful change (25-66%) from baseline to day 90. Physical well-being had the largest proportion of participants with meaningful improvement (48%), followed by overall HRQOL (47%) and pain interference (46%). Analyses of differences by race/ethnicity indicated that a larger proportion of racial/ethnic minority vs. NHW participants reported meaningful improvement in global pain (54% vs. 18%; p=0.002) and fatigue (43% vs. 28%; p=0.055), though the difference in fatigue did not reach statistical significance. There were no other differences in meaningful PRO change by race/ethnicity (p-values>0.05).

Conclusions: Consistent with our hypothesis, the majority of RRMM patients treated with CAR T in standard of care reported meaningful improvement or stable/no meaningful change in PROs from pre-CAR T to day 90 post-infusion. Notably, almost half of all participants reported meaningful improvements in physical well-being, overall HRQOL, and pain interference, indicating that a substantial proportion of CAR T recipients perceive meaningful benefits for important PROs. Racial/ethnic minority participants were more likely than NHW participants to report meaningful improvement in global pain and fatigue, suggesting that racial/ethnic minority patients may uniquely benefit from CAR T. These findings should be further explored in future studies with larger cohorts of diverse RRMM patients treated with CAR T.

Baz:Abbvie: Research Funding; BRISTOL MYERS SQUIBB: Research Funding; Celgen: Research Funding; Cellectar: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm Therapeutics: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Regeneron: Research Funding. Shain:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy; Karyopharm: Research Funding; Abbvie: Research Funding; BMS: Consultancy, Research Funding; Amgen: Research Funding; Takeda: Consultancy; Glaxo Smith Kline: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm, Janssen, Adaptive Biotechnologies, GlaxoSmithKline, BMS, Sanofi, and Regeneron: Honoraria; Adaptive Biotech: Consultancy. Blue:Sanofi: Speakers Bureau; Pfizer Pharmaceuticals, Oncopeptides, Takeda, Abbvie, Janssen, and Kite Pharmaceuticals: Consultancy. Grajales-Cruz:Cellectar, Janssen, Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen, Sanovi: Speakers Bureau. Alsina:BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. Freeman:Abbvie: Consultancy; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding; Amgen: Consultancy; Incyte: Consultancy; ONK therapeutics: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy, Honoraria, Research Funding. Castaneda:Legend Biotech: Consultancy; Janssen: Consultancy; BMS: Consultancy. Nishihori:Novartis: Research Funding; ImmunoGen: Consultancy; Medexus: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Other: drug only supply to the institution. Liu:BioLineRx: Consultancy, Honoraria. Locke:Aptitude Health: Honoraria; Caribou: Consultancy; Iovance: Consultancy; Cowen: Consultancy; A2: Consultancy; BioPharma: Honoraria; ASH: Honoraria, Other: Travel support; Janssen: Consultancy; Society for Immunotherapy of Cancer: Honoraria; Communications CARE Education: Honoraria; Moffit Cancer Center: Patents & Royalties: cellular immunotherapy; Emerging Therapy Solutions Gerson Lehman Group: Consultancy; ecoR1: Consultancy; Novartis: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Umoja: Consultancy; Kite, a Gilead Company: Consultancy, Other: Travel support, Research Funding; Gilead Company: Consultancy; iMedX: Honoraria; GammaDelta Therapeutics: Consultancy; Calibr: Consultancy; Cellular Biomedicine Group: Consultancy; Legend Biotech: Consultancy; Celgene: Consultancy; BMS: Consultancy, Research Funding; Allogene: Consultancy, Research Funding; Amgen: Consultancy; Sana: Consultancy; Wugen: Consultancy; Clinical Care Options Oncology: Honoraria; Gerson Lehrman Group (GLG): Consultancy; Pfizer: Consultancy; CERo Therapeutics: Research Funding; 2SeventyBio: Research Funding; National Cancer Institute: Research Funding; Leukemia and Lymphoma Society Scholar in Clinical Research: Research Funding; Aptitude Health: Honoraria. Jim:Kite Pharma: Research Funding; SBR Biosciences: Consultancy. Hansen:Pfizer: Consultancy; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy; BMS: Consultancy, Research Funding. Peres:Karyopharm Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding.