CD19-Directed CART Therapy for T Cell/Histiocyte Rich Large B-Cell Lymphoma: A CIBMTR Analysis

Le résumé fourni par la source

T cell/Histiocyte Rich Large B-cell Lymphoma (THRLBCL) is a rare histologic variant of large B-cell lymphoma (LBCL) with less favorable treatment outcomes. While CD19-directed chimeric antigen receptor T-cell (CART) therapy is effective in large B-cell lymphoma, its role in THRLBCL is controversial. In a recent case series, 9 out of 9 THRLBCL patients experienced treatment failure within 90 days post-CART infusion (Trujillo et al., Blood 2021). We therefore investigated CART outcomes for THRLBCL in the CIBMTR registry. Adult patients (≥ 18 years) with THRLBCL who received commercial CD19-directed CART between 2015 and 2022 were identified in the CIBMTR registry. Patients were excluded if they had received prior adoptive cellular therapy. Overall survival (OS) was the primary outcome. Secondary outcomes included progression-free survival (PFS), incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurologic syndrome (ICANS), and cumulative incidence of relapse/progression (rel/prog) and non-relapse mortality (NRM). A total of 58 patients from 37 centers were included in the analysis. The median age was 49 years (range: 19-76), with 12 patients (21%) older than 65 years (Table). Axicabtagene ciloleucel was the predominant CART product (69%). Most patients (67%) had early initial relapse of disease, including 45% (n=26) with primary refractory disease. The median number of prior therapies was 3 (range: 1-7). A Karnofsky performance status < 90 was reported in 41% (n=24) of patients. With a median follow-up of 23 months (range: 2-48) from CART infusion, 2-year OS was 42% (95% CI: 27-57) and PFS was 29% (95% CI: 17-43; Figure A). In a univariable analysis, only poor performance status pre-infusion was associated with significantly higher risk for mortality (Figure B). The 2-year cumulative incidences of rel/prog and NRM were 69% (95% CI: 55-82) and 2% (95% CI: 0-8), respectively. Grade ≥ 3 CRS and ICANS were observed in 4 (7%) and 9 (15%) patients, respectively. In this largest analysis of THRLBCL treated with CD19-directed CART, approximately 30% of patients were alive and progression-free 2 years following CART infusion. Despite a high risk of relapse (69% at 2 years), these results suggest that a subset of patients with THRLBCL may have durable response with CART. Further study is required to identify predictors of treatment success.

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