ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Relapsed Refractory Multiple Myeloma after Failure of Chimeric Antigen Receptor T-Cell Therapy

Abstract

Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the management of relapsed and/or refractory multiple myeloma (RRMM). However, CAR-T treatment failure is not uncommon and remains a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post CAR-T failures in RRMM. The American Society for Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines conducted an online cross-sectional survey between September 2023 and December 2023 to determine the myeloma, transplantation and cellular therapy physicians' practice patterns for surveillance, diagnosis, and management of CAR-T failure. The intent of this survey was to understand clinical practice patterns and identify areas for further investigation. E-mail surveys were sent to 1311 ASTCT physician members and 80 (6.1%) respondents completed the survey who identified as 58% white, 66% male, and 51% had >10 years of clinical experience. Eighty-nine percent of respondents were affiliated with university/teaching centers; 56% had myeloma-focused transplantation and/or cellular therapy practices. Post-CAR-T surveillance laboratory studies were commonly done every 4 weeks, while surveillance bone marrow biopsies and/or imaging surveillance were most commonly done at 3 months. Sixty-four percent of respondents would often or always consider biopsy or imaging to confirm relapse. The most popular post- CAR-T-failure rescue regimen was a GPRC5D-directed immunotherapy (30%) for relapses occurring ≤3 months and BCMA-directed bispecific therapies (32.5%) for relapses >3 months. Forty-one percent of respondents endorsed post-CAR-T prolonged cytopenia as "often" or "always" being a barrier to next-line therapy; 53% had offered stem cell boost as a mitigation approach. Substantial cross-center variation in practice patterns raises the need for collaborative studies and expert clinical recommendations to describe best practices for post CAR-T disease surveillance, optimal work-up for treatment failure, and choice of rescue therapies.