ASTCT Committee on Practice Guidelines Survey on Evaluation & Management of Diffuse Large B-cell Lymphoma after Failure of Chimeric Antigen Receptor T Cell Therapy (CAR-T) Therapy

Abstract

Chimeric antigen receptor T-cell therapy (CAR-T) is a major advance in managing aggressive relapsed or refractory B-cell lymphomas; however, relapses are frequent and pose a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post-CAR-T failures. The American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines conducted an online cross-sectional survey between August 2021 and October 2021 to determine the U.S. lymphoma and transplantation and cellular therapy physicians' practice patterns for the detection and diagnosis of CAR-T failure, as well as management strategies for diffuse large B-cell lymphoma in this particular setting. E-mail surveys were sent to 901 potential participants, of which 174 (19%) completed the survey. Responders were mainly White (51.2%), male (70.7%), and with >10 years of practice experience (51.2%). Overall, 87% of the responders were affiliated with university/teaching centers; 54.6% had general oncology practices, and 45.4% had lymphoma-focused transplantation/cellular therapy practices. The most common periods to perform surveillance scans were at 3 months and 12 months after CAR-T infusion. Overall, 88.5% of responders would often or always consider a biopsy to confirm relapse and 89% would routinely check for the persistence of the antigen targeted by the CAR (e.g., CD19 in the case of CD19 CAR-T). The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. Twenty-seven percent of responders chose this regimen for CD19 positive relapse, whereas 31% of responders did so for CD19 negative relapse. Overall, 88.5% of responders favored consolidative allogeneic hematopoietic cell transplantation after response to salvage, whereas 51.2% of physicians would consider autologous hematopoietic cell transplantation in transplantation-naïve patients. There is substantial cross-center variation in surveillance, diagnosis, and management of CAR-T failure. Prospective clinical trials evaluating novel agents in this setting are urgently needed to identify best management strategies.