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

• POD post-CAR-T for R/R MCL is associated with short OS and time from CAR-T infusion to POD, predicted inferior OS in this setting

• Bispecific antibodies and combination small molecule approaches have activity in treating progressive disease post-CAR-T for R/R MCL

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.