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
Authors: Ferraris Carina E. , Li Xiaoyin , De Avila Gabriel , Gudenkauf Lisa M. , Hoogland Aasha I. , Nguyen Oanh , Rodriguez Yvelise , Crowder Sylvia L. , Parker Nathan , Carson Tiffany L. , Baz Rachid C. , Shain Kenneth H. , Blue Brandon , Grajales-Cruz Ariel , Alsina Melissa , Freeman Ciara Louise , Castaneda Omar , Nishihori Taiga , Liu Hien , Locke Frederick L. , Jim Heather S.L. , Hansen Doris K. , Peres Lauren C. , Oswald Laura B. 
Published: December 2024

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&gt;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&gt;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.