Evolving Transplantation Patterns for Mantle Cell Lymphoma in the Era of Chimeric Antigen Receptor Therapy.

Transplantation and Cellular Therapy(2024)

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Introduction Mantle cell lymphoma is an aggressive lymphoma with poor survival after chemotherapy alone. Both autologous (auto) and allogeneic (allo) transplants have improved outcomes over the years, but transplant strategies most beneficial for MCL are not clearly defined Recently, chimeric antigen therapies (CAR T) have changed the landscape for relapsed/refractory MCL patients not candidates for conventional transplants. Methods Patient Population: A total of 77 patients underwent transplant for diagnosis of MCL at Penn State Cancer Institute, between January 2002 and July 2023. Median follow up was 13.6 years (80 days-5000 days).Patient Characteristics: A total of 77 patients (67 M: 10 F) underwent transplants, including autologous (n=34), allogeneic (n=34), and CAR T (n=9). Since 2020, 19 transplants were performed,. CAR T (n=9) auto transplants (n=9) and allogeneic transplants (n=1). Relapsed and refractory MCL (n=9) patients received CAR T whereas patients achieving CR 1 (n=9)and PR1 (n=1) received auto transplants.Median age at the time of transplant was 59 (37-70)years for auto, 56(33-67) years for allo and 63 (55 -75) years for CAR T respectively. Donor type for the 34 allografts included haploidentical donors (n=1), MSD (n=16), MUD (n=17); 34 recipients received autografts. Source of graft was peripheral blood in 76 patients, and only one was bone marrow. Most patients were Caucasian (n= 73), with few Hispanic (2), African American (1), or Asian (1). Disease status at transplant was CR (CR1 or CR2) (n=38), PR (PR1 or PR2) (n=11), and primary induction failure or relapsed/refractory (n=28). Outcomes One year and 3 yr overall survival (OS) was 93.8 % and 79.4% respectively for autologous (auto) transplants (P = 0.053). For Allogeneic (allo) transplants, one year and 3 year OS was 64.5%and 54.7% respectively. For CAR-T therapy OS was 85.7% at one yr and 3 yr OS was not reached(NR)Progression free survival at 1 yr and 3 yr for auto transplants was 86.3% and 66.3%; for allo: 52.5%and 45.5% and for CART: 61 % at one yr and 3 yr PFS was NR. P = 0.099 . Primary cause of death was TRM (n= 8) (GVHD=4; Pulmonary=3; MOF=2) and disease progression (n=8); unknown (n= 4); other (n=1).Primary cause of death for CAR T therapy was grade IV ICANS and disease progression. Conclusion Both autologous and allogeneic transplants can be performed as consolidation therapy for MCL but benefit of allogenic transplant is offset by increased risk of transplant related mortality and GVHD. Recently CAR T therapies have changed the landscape of MCL treatment algorithm and non-blastoid histology MCL achieve CR without increased risk of GVHD. In the era of CAR T therapies for MCL, CR at the time of transplant is no longer a factor for long term outcomes of MCL patients. Randomized studies or larger retrospective CIBMTR data analysis may be important to answer best transplant strategy for MCL patients.
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