Allogeneic Transplant and Car-T Therapy After Autologous Transplant Failure in DLBCL: A Noncomparative Cohort Analysis

Authors

Mehdi Hamadani
Ajay K Gopal
Marcelo Pasquini
Soyoung Kim
Xianmiao Qiu
Sairah Ahmed
Aleksandr Lazaryan
Vijaya Raj Bhatt
Andrew Daly
Premal Lulla
Stefan Ciurea
Jordan Gauthier
Vaibhav Agrawal
Natalie S Grover
Lazaros Lekakis
Dipenkumar Modi
Parastoo B Dahi
Megan M Herr
P Connor Johnson
Hamza Hashmi
Peiman Hematti
Frederick L Locke

Publication Date

1-25-2022

Journal

Blood Advances

DOI

10.1182/bloodadvances.2021005788

PMID

34673903

PMCID

PMC8791562

PubMedCentral® Posted Date

1-18-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Allografts, Autografts, Cohort Studies, Hematopoietic Stem Cell Transplantation, Humans, Lymphoma, Large B-Cell, Diffuse, Neoplasm Recurrence, Local, Receptors, Chimeric Antigen

Abstract

Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P < .001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.

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