Allogeneic transplant following CAR T-cell therapy for large B-cell lymphoma

Abstract

Allogeneic hematopoietic cell transplantation (alloHCT) can potentially salvage large B-cell lymphoma (LBCL) patients experiencing treatment failure after chimeric antigen receptor T-cell therapy (CAR-T). Nonetheless, data on the efficacy and toxicities of alloHCT after receipt of CAR-T are limited. We report a multicenter retrospective study assessing the safety, toxicities, and outcomes of alloHCT in LBCL patients following CAR-T failure. Eighty-eight patients with relapsed, refractory LBCL received an alloHCT following anti-CD19 CAR-T failure. The median number of lines of therapy between CAR-T infusion and alloHCT was 1 (range 0-7). Low intensity conditioning was used in 77% (n=68) and peripheral blood was the most common graft source (86%, n=76). The most common donor types were matched unrelated donor (39%), followed by haploidentical (30%) and matched related donor (26%). Median follow-up of survivors was 15 months (range 1-72). One-year overall survival, progression-free survival, and graft-versus-host disease-free relapse-free survival were 59%, 45%, and 39% respectively. One-year non-relapse mortality and progression/relapse were 22% and 33% respectively. On multivariate analysis,

Relapsed or refractory large B‐cell lymphoma after chimeric antigen receptor T‐cell therapy: Current challenges and therapeutic options

“…48 In the multivariate analysis, fewer than two lines of intervening therapy between CAR-T therapy and allo-HCT and CR before allo-HCT were associated with better outcomes. 48 Thus, allo-HCT after CAR-T therapy failure can be an alternative with durable responses in a subset of patients. The feasibility of allo-HCT consolidation to treat R/R DLBCL after CAR-T therapy is restricted due to limited salvage options and recipient comorbidities.…”

“…At 1 year, the OS, PFS and graft‐versus‐host disease‐free relapse‐free survival was 59%, 45% and 39% respectively 48 . In the multivariate analysis, fewer than two lines of intervening therapy between CAR‐T therapy and allo‐HCT and CR before allo‐HCT were associated with better outcomes 48 . Thus, allo‐HCT after CAR‐T therapy failure can be an alternative with durable responses in a subset of patients.…”

“…A recent study reported on the outcomes of 88 patients with R/R DLBCL who received an allo‐HCT after CAR‐T therapy failure. At 1 year, the OS, PFS and graft‐versus‐host disease‐free relapse‐free survival was 59%, 45% and 39% respectively 48 . In the multivariate analysis, fewer than two lines of intervening therapy between CAR‐T therapy and allo‐HCT and CR before allo‐HCT were associated with better outcomes 48 .…”

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms?

“…Limited data exist to document the safety and efficacy of allo-SCT after CAR-T therapy, and most of the evidence has come from a small patient series. Zurko et al [ 29 ] presented data for patients treated at 18 US academic medical centers. The 88 patients included in the analysis had a median age of 54.…”

The place of allogeneic stem cell transplantation in aggressive B-cell non-Hodgkin lymphoma in the era of CAR-T-cell therapy

“…The 1-year NRM was 22%, and the 1-year OS and PFS were 59 and 55%, respectively. In the multivariate analysis, the number of lines of therapy between CAR-T-cell therapy and ALLO-SCT and disease status at the time of ALLO-SCT were the most important prognostic factors for survival ( 73 ).…”