Autologous Transplant or CAR-T as Consolidation Options in MYC Rearranged Large B-Cell Lymphoma Patients in Remission After Salvage Treatments.

in American journal of hematology by Fateeha Furqan, Kwang W Ahn, Manmeet Kaur, Jinalben Patel, Stephen Ansell, Farrukh T Awan, John Baird, Evandro Bezerra, Umar Farooq, Henry Fung, Arushi Khurana, Lazaros Lekakis, Forat Lutfi, John McCarty, Akash Mukherjee, Rajneesh Nath, Jason Romancik, Stephen J Schuster, Melody Smith, Allison Winter, Cameron Turtle, Craig Sauter, Mazyar Shadman, Alex Herrara, Mehdi Hamadani

TLDR

  • The study compared CAR-T and auto-HCT in patients with R-MYC LBCL who achieved a CR/PR with salvage therapies and found that CAR-T was associated with lower overall survival, but not with significantly different PFS, risk of relapse, or post-relapse survival.
  • These findings support consideration for auto-HCT in patients with R-MYC LBCL who achieve a CR/PR after salvage therapies, particularly in regions with no or limited access to CAR-T.

Abstract

Although recent studies have demonstrated the efficacy of chimeric antigen receptor T-cell (CAR-T) therapy in relapsed large B-cell lymphoma (LBCL) with MYC rearrangement (R-MYC), the data comparing CAR-T to autologous hematopoietic cell transplant (auto-HCT) in such patients who achieve a complete or partial response (CR/PR) after salvage therapies are limited. We compared the clinical outcomes of patients with R-MYC LBCL (including double and triple hit lymphomas) who underwent CAR-T or auto-HCT after achieving a CR/PR with salvage therapies using the Center for International Blood & Marrow Transplant Research registry. Among the 252 patients (auto-HCT = 98, CAR-T = 154), relative to auto-HCT, CAR-T was associated with significantly lower overall survival (OS) (Hazard Ratio [HR] 2.09, 95% CI 1.38-3.15, p < 0.001) on multivariate analysis. There were no differences in progression-free survival (PFS) (HR 1.21, 95% CI 0.81-1.8 p = 0.36), risk of relapse (HR 1.1, 95% CI 0.71-1.69 p = 0.68), nonrelapse mortality (NRM) (HR 1.74, 95% CI 0.64-4.7 p = 0.28) while the post-relapse survival was longer in auto-HCT relative to CAR-T (HR 1.93, 95% CI 1.21-3.06 p = 0.01). On propensity score matched analysis accounting for differences in characteristics across the two cohorts, we detected no significant differences in OS (HR 1.72, 95% CI 0.92-3.21 p = 0.09), PFS (HR 1.04, 95% CI 0.64-1.68 p = 0.88), NRM (HR 1.22, 95% CI 0.35-4.2 p = 0.76), relapse (HR = 0.93, 95% CI 0.54-1.6 p = 0.8) and post-relapse survival (HR 2.25, 95% CI 0.98-5.17, p = 0.06). These data, although retrospective, support consideration for auto-HCT in patients with R-MYC LBCL who achieve a CR/PR after salvage therapies, particularly in regions with no or limited access to CAR-T.

Overview

  • The study compared the clinical outcomes of patients with R-MYC LBCL who underwent CAR-T or auto-HCT after achieving a CR/PR with salvage therapies using the Center for International Blood & Marrow Transplant Research registry.
  • The study focused on patients with relapsed large B-cell lymphoma (LBCL) with MYC rearrangement who received either CAR-T therapy or autologous hematopoietic cell transplant (auto-HCT) after achieving a complete or partial response with salvage therapies.
  • The primary objective of the study was to compare the clinical outcomes of CAR-T and auto-HCT in this patient population, with a specific focus on overall survival, progression-free survival, risk of relapse, non-relapse mortality, and post-relapse survival.

Comparative Analysis & Findings

  • The study found that CAR-T therapy was associated with significantly lower overall survival (OS) compared to auto-HCT in patients with R-MYC LBCL who achieved a CR/PR with salvage therapies.
  • However, there were no significant differences in progression-free survival (PFS), risk of relapse, non-relapse mortality, or post-relapse survival between the two treatment groups.
  • In a propensity score-matched analysis, the study detected no significant differences in OS, PFS, NRM, relapse, and post-relapse survival between the CAR-T and auto-HCT groups.

Implications and Future Directions

  • These findings support consideration for auto-HCT in patients with R-MYC LBCL who achieve a CR/PR after salvage therapies, particularly in regions with no or limited access to CAR-T.
  • Future studies should aim to address the limitations of this retrospective analysis, such as the potential selection biases and the lack of control for confounding variables.
  • Prospective trials comparing CAR-T and auto-HCT in this patient population are necessary to confirm the findings of this study and provide more definitive treatment recommendations.
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