CT-1272: Bridging to Allogeneic Hematopoietic Cell Transplantation Following CD19-Directed CAR-T Therapy in Relapsed/Refractory Large B-Cell Lymphoma: A Systematic Review of Outcomes and Prognostic Indicators

Document Type

Conference Proceeding

Publication Date

9-1-2025

Publication Title

Clin Lymphoma Myeloma Leuk

Abstract

Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies have reshaped the therapeutic paradigm for relapsed/refractory large B-cell lymphoma (R/R LBCL). Yet, real-world durability remains limited, with up to 60% of patients progressing within 1 year. Allogeneic hematopoietic cell transplantation (allo-HCT) is increasingly considered as consolidative or salvage therapy, though its role after CAR-T therapy remains ill-defined. Objective: To systematically evaluate published outcomes of allo-HCT following CAR-T therapy in R/R LBCL and identify clinical or biological predictors of benefit. Design: A systematic review was conducted according to PRISMA guidelines. PubMed, Embase, and ClinicalTrials.gov were searched for studies published from 2017 to 2025. Inclusion criteria encompassed prospective or retrospective series reporting outcomes of adult patients with R/R LBCL undergoing allo-HCT following CAR-T therapy. Data on overall survival (OS), progression-free survival (PFS), nonrelapse mortality (NRM), and graft-vs-host disease (GVHD) were extracted. Setting and Patients: Seven studies comprising 142 patients were included. Median age ranged from 48 to 61 years. Most received axicabtagene ciloleucel or tisagenlecleucel. The interval between CAR-T infusion and allo-HCT ranged from 50 to 120 days. Approximately 60% to 75% of patients underwent transplant in complete response (CR), while others proceeded with partial response or stable disease. Intervention: Allo-HCT following CAR-T, using reduced-intensity or myeloablative conditioning. Donor sources included matched unrelated (44%–58%), matched sibling (18%–33%), and haploidentical (up to 15%) donors. GVHD prophylaxis regimens varied, with the most common post-transplant regimens based on cyclophosphamide and tacrolimus. Main Outcome Measures: Across studies, 1-year OS ranged from 36% to 59%, with PFS ranging from 30% to 45%. NRM ranged from 17% to 22%. Acute GVHD grade ≥2 occurred in 28% to 36%, and chronic GVHD in up to 40%. Durable remissions were predominantly observed in patients bridged in CR with minimal disease burden and fewer than two intervening salvage lines after CAR-T therapy. Conclusions: Allo-HCT remains a feasible and potentially curative option in select patients following CD19-directed CAR-T therapy failure. Optimal candidates are those with early response and minimal disease pre-HCT. The heterogeneity of conditioning intensity, donor selection, and timing limits direct comparability. Prospective biomarker-guided trials are warranted to define transplant eligibility and improve sequencing after CAR-T therapy in R/R LBCL.

Volume

25

First Page

S1054

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