Citations 1
Treatment and outcomes of progression of disease post–CAR T-cell therapy in mantle cell lymphoma: a multicenter analysis
Epstein‐Peterson, Zachary D. , Lionel, Anath C. , Joseph, Ashlee , Drill, Esther , Atallah‐Yunes, Suheil Albert , Brooks, Taylor , Chong, Elise A. , Chong, Emeline R. , Cruz, Jamie Dela , Frank, Matthew J. , Jacobson, Caron A. , Beyar‐Katz, Ofrat , Maddocks, Kami J. , McLoughlin, Daniel E. , Navalekar, Rohin, Ryan, Christine E. , Sauter, Craig S. , Sharma, Samanvaya , Shukla, Navika , Therwhanger, Dylan , Besien, Herman J. van, Varon, Ben , Yamshon, Samuel , Palomba, M. Lia , Kumar, Anita , Brooks, Taylor R , Kamdar, Manali , Karmali, Reem , Matasar, Matthew , McLoughlin, Daniel , Rhodes, Joanna , Riedell, Peter A , Ryan, Christine E , Salles, Gilles A , Sawalha, Yazeed , Sharma, Samanvaya , Shouval, Roni , Therwhanger, Dylan , van Besien, Herman , Varon, Ben , Wang, Yucai , Yamshon, Samuel , Zelenetz, Andrew D , Jain, Preetesh , Kumar, Anita , Chong, Elise A , Joseph, Ashlee , Atallah-Yunes, Albert , Ip, Andrew , Iqbal, Madiha , Kamdar, Manali , Karmali, Reem , Matasar, Matthew J. , Merryman, Reid W. , Muñoz, Javier , Navalekar, Rohini, Rhodes, Joanna , Riedell, Peter A. , Salles, Gilles , Sawalha, Yazeed , Wang, Yucai , Zelenetz, Andrew D. , Jain, Preetesh
Blood Advances | August 5, 2025 | Volume: 9 | Issue: 21 | Pages: 5654-5662
10.1182/bloodadvances.2025016315
Abstract The treatment patterns and clinical outcomes for patients experiencing progression of disease (POD) following CD19-directed chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory (R/R) mantle cell lymphoma (MCL) are undefined. We identified all patients who received CD19-directed CAR T-cell therapy for R/R MCL therapy across 15 international centers, and studied those experiencing POD post–CAR T-cell therapy in detail. We extracted clinical/treatment/pathologic variables, and associated these features with survival outcomes. In total, 384 patients received CAR T-cell therapy, and 135 (35%) experienced POD. POD occurred at a median of 6 months following CAR T-cell therapy infusion, and most (64%) patients with POD had complete response as best response to CAR T-cell therapy. Tumor features at POD included blastoid/pleomorphic morphology in 29 of 78 (37%) patients, and TP53 mutation in 21 of 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 bispecific antibodies (13 patients; ORR, 67%). Among patients experiencing POD, the median progression-free survival and overall survival (OS) were 2.5 months and 5.4 months, respectively, from POD. Lack of response to CAR T-cell therapy and short time from CAR T-cell therapy infusion to POD (<3 vs 3-6 vs >6 months), among other factors, were associated with inferior OS after POD. In conclusion, we confirm the challenging prognosis for patients experiencing POD following CD19 CAR T-cell therapy for R/R MCL, and establish a benchmark for future investigations in this patient population.