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

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-naive 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. (C) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Automated summary

Chimeric antigen receptor T-cell therapy (CAR-T) is a significant advancement in managing aggressive relapsed or refractory B-cell lymphomas, but frequent relapses remain a major challenge. There is substantial variability in assessing and managing post-CAR-T failures across transplantation and cellular therapy programs. A survey was conducted among lymphoma, transplantation, and cellular therapy physicians in the United States to determine their practice patterns for the detection, diagnosis, and management of CAR-T failure in diffuse large B-cell lymphoma. The survey revealed significant differences in surveillance, diagnosis, and treatment approaches for CAR-T failure.