Outcomes of autologous transplant, allogeneic transplant, and car t cell therapy in tp53 altered mantle cell lymphoma: a multi‐institution retrospective analysis

Introduction: TP53 alterations are associated with poor prognosis in mantle cell lymphoma (MCL). In trials of intensive chemotherapy and autologous hematopoietic cell transplant (auto-HCT), patients (pts) with TP53 mutations had an overall survival (OS) of 1.8 years (yrs) compared to 12.7 yrs for unmutated. Optimal treatment to achieve durable remission is unknown. We report transplant and cellular therapy outcomes of a large cohort of pts with TP53 altered MCL. Methods: We conducted a multi-site retrospective study of pts with MCL harboring TP53 mutation, deletion, or overexpression at 25 sites in the United States from 1998 to 2022. For outcomes after auto-HCT, allogeneic transplant (allo-HCT), and chimeric antigen receptor T cell therapy (CAR-T), TP53 alteration must have been present at time of this therapy. Event free survival (EFS) after auto-HCT, allo-HCT, and CAR-T was defined as time from treatment to relapse, subsequent therapy, or death. Results: We identified 254 pts with TP53 altered MCL, with median 4.8 yrs follow up and baseline characteristics described in table 1. TP53 alteration was found in 75% at diagnosis. OS for the total cohort was 6.3 yrs from diagnosis. There was no difference in OS based on type of TP53 alteration or Ki-67. MIPI high risk (p < 0.0001) and blastoid/pleomorphic variant (p = 0.02) predicted shorter OS. There were 75 consolidative auto-HCT eligible pts, defined as age 65 and under with no events within 6 months after first line therapy. Of these, 42 received auto-HCT in first remission. Median EFS was 4.0 yrs in pts who received auto-HCT and 1.5 yrs for no auto-HCT (p < 0.01). There was no difference in OS (p = 1.0). Among pts with a TP53 mutation, EFS was 2.1 yrs with auto-HCT (N = 10) and 2.2 yrs without (N = 18) (p = 0.5). Allo-HCT was used in 24 pts, after a median of 2 lines of therapy. 46% had prior Bruton tyrosine kinase inhibitor (BTKi) treatment. Allo-HCT was matched in 74%, related donor in 50%, myeloablative in 25%, using post-transplant cyclophosphamide in 46%, and ATG in 13%. With median follow up 5.9 yrs, median EFS after allo-HCT was 1.5 yrs and OS 5.4 yrs, with no difference according to type of TP53 alteration. There were 5 pts still in remission over 5 years from allo-HCT. CAR-T was used in 37 pts, with median 3 prior lines of therapy. 92% had prior BTKi and 86% received bridging therapy. With median follow up 1.3 yrs, median EFS after CAR-T was 0.9 yrs and median OS 1.4 yrs, with no difference based on type of TP53 alteration. Conclusion: Here we report the largest pooled analysis of transplant and cellular therapy for TP53 altered MCL. Within this high risk cohort, high MIPI and blastoid/pleomorphic morphology predicted even shorter survival. Auto-HCT was associated with improved EFS in all TP53 altered, but not among TP53 mutated. CAR-T and allo-HCT do not appear to abrogate the poor prognosis conferred by TP53 mutation, emphasizing the need for targeted clinical trials in this population. Keywords: aggressive B-cell non-Hodgkin lymphoma, cellular therapies, stem cell transplant Conflicts of interests pertinent to the abstract S. D. Smith Consultant or advisory role: Astrazeneca, Beigene, KITE pharma Research funding: Astrazeneca, Beigene, Genentech D. Bond Consultant or advisory role: SeaGen, KITE/Gilead, Nurix Research funding: Nurix, Novartis P. Ramakrishnan Geethakumari Consultant or advisory role: KITE, BMS, Rafael Pharma, Pharmacyclics LLC, ADC Therapeutics, Cellectar Biosciences, Ono Pharma