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Treatment and outcomes of progression of disease post-CAR T-cell therapy in mantle cell lymphoma: a multicenter analysis.

Treatment and outcomes of progression of disease post-CAR T-cell therapy in mantle cell lymphoma: a multicenter analysis. Blood advances Epstein-Peterson, Z. D., Lionel, A. C., Joseph, A., Drill, E., Atallah-Yunes, S. A., Brooks, T. R., Chong, E. A., Chong, E. R., Dela Cruz, J., Frank, M. J., Ip, A., Iqbal, M., Jacobson, C. A., Kamdar, M., Karmali, R., Beyar-Katz, O., Maddocks, K. J., Matasar, M. J., McLoughlin, D., Merryman, R. W., Munoz, J., Navalekar, R., Rhodes, J. M., Riedell, P. A., Ryan, C. E., Salles, G. A., Sauter, C. S., Sawalha, Y., Sharma, S., Shouval, R., Shukla, N., Therwhanger, D., van Besien, H. J., Varon, B., Wang, Y., Yamshon, S., Zelenetz, A. D., Palomba, M. L., Jain, P., Kumar, A. 2025

Abstract

The treatment patterns and clinical outcomes for patients experiencing progression-of-disease (POD) following CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR-T for R/R MCL therapy across 15 international centers and studied those experiencing POD-post-CAR-T in detail. We extracted clinical/treatment/pathologic variables and associated these features with survival outcomes, measured from time of POD. 384 total patients received CAR-T therapy and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR-T infusion and most (64%) patients with POD had complete response as best response to CAR-T. Tumor features at POD included blastoid/pleomorphic morphology in 29/78 (37%) patients and TP53 mutation in 21/41 (51%) patients. Following POD, 17 patients received no further therapy, 13 underwent local therapy, and 105 received systemic therapy. The most common first-line systemic therapies were chemo(immuno)therapy [22 patients, overall response rate (ORR) 40%], pirtobrutinib (17 patients, ORR 36%), and bi-specific antibodies (BsAb), received by 13 patients, ORR 67%. Among patients experiencing POD, the median progression-free and overall survival was 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR-T and short time from CAR-T infusion to POD (<3 months vs. 3-6 months vs. >6 months), among other factors, were associated with inferior overall survival post-POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR-T for R/R MCL and establish a benchmark for future investigations in this patient population.

View details for DOI 10.1182/bloodadvances.2025016315

View details for PubMedID 40763269