Trajectories of Patient-Reported Outcomes after Idecabtagene Vicleucel Vs. Ciltacabtagene Autoleucel CAR T-Cell Therapy Among Patients with Relapsed/Refractory Multiple Myeloma in Standard of Care
Authors: Li Xiaoyin , Ferraris Carina E. , 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 therapy (CAR T) has revolutionized treatment for relapsed/refractory multiple myeloma (RRMM). Both FDA-approved CAR Ts for RRMM, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), are associated with noteworthy clinical benefits. In addition, patient-reported outcomes (PRO) data from clinical trials show that ide-cel and cilta-cel are associated with meaningful improvements in health-related quality of life (HRQOL) and decreases in patient-reported symptom burden. However, PRO data from RRMM patients treated in standard of care are limited, and we are not aware of any studies that have directly compared PROs between patients treated with ide-cel vs. cilta-cel. To address this gap, we longitudinally assessed PROs in a cohort of RRMM patients treated with CAR T in standard of care and compared changes in PROs between treatments.

Methods: Patients with RRMM scheduled to receive standard of care ide-cel or cilta-cel CAR T were recruited between September 2022 and June 2024. Participants completed PRO surveys at baseline (i.e., pre-lymphodepleting chemotherapy), day 0 (i.e., day of CAR T infusion) and on days 7, 14, 21, 30, 60, and 90 post-CAR T. At each timepoint, participants completed the Functional Assessment of Cancer Therapy-General (FACT-G), which assesses overall HRQOL and four well-being domains (i.e., physical, social, emotional, functional). Participants also completed PRO Measurement Information System (PROMIS) measures assessing patient functioning (i.e., physical, social, and cognitive function) and symptoms (i.e., depression, anxiety, fatigue, sleep disturbance, pain interference, global pain). Discontinuous, or piecewise, growth curve models were used to test the hypotheses that 1) PROs worsen from baseline to day 7 and improve from day 7 to day 90, and 2) PRO trajectories differ between patients treated with ide-cel vs. cilta-cel.

Results: Participants (N=99) were 49 patients treated with ide-cel and 50 patients treated with cilta-cel. Most were male (61%), and the median age was 66 years (range 45-84). Patients treated with ide-cel (vs. cilta-cel) were older (M=71.2, SD=9.9 vs. M=63.2, SD=7.5; t=-4.5, p&lt;0.001). There were no other demographic differences between groups at baseline. Patients slated for cilta-cel (vs. ide-cel) had better social well-being (p=0.047) and less sleep disturbance at baseline (p=0.047), though differences were small. There were no other PRO differences between groups at baseline. Across all participants, several PROs followed a pattern of significant worsening from baseline to day 7 and subsequent improvement from day 7 to day 90 (p-values&lt;0.05): overall HRQOL, physical well-being, social well-being, functional well-being, physical function, social function, fatigue, and sleep disturbance. Emotional well-being improved from baseline to day 7 (p&lt;0.01) and then remained stable. There were no significant changes from baseline to day 7 and from day 7 to day 90 for cognitive function, depression, anxiety, pain interference, or global pain (p-values&gt;0.05). In analyses comparing ide-cel vs. cilta-cel, patients treated with cilta-cel reported greater decreases in social well-being from baseline to day 7 (β=0.05, p&lt;0.05) and greater improvements from day 7 to day 90 (β=-0.06, p&lt;0.05). There were no other differences in PRO trajectories between patients treated with ide-cel vs. cilta-cel (p-values&gt;0.05).

Conclusions: This was the first study to examine PRO trajectories after ide-cel and cilta-cel CAR T in a cohort of RRMM patients treated in standard of care using advanced statistical modeling. As hypothesized, many aspects of HRQOL and symptom burden initially worsened after CAR T but later rebounded to baseline levels or better by day 90 post-treatment. Contrary to hypotheses, there were few differences in PRO trajectories between ide-cel and cilta-cel. As an exception, potential differences in social well-being should be investigated further and could have implications for tailored supportive care strategies based on CAR T regimen. Overall, patients treated with both ide-cel and cilta-cel CAR T for RRMM in standard of care experienced similar PRO trajectories and benefits post-treatment. Future analyses should consider differences in average onset of toxicities and clinical characteristics of the patient samples.