CD19 CAR-T CELL THERAPY IN RELAPSED/REFRACTORY SOLID ORGAN TRANSPLANT-RELATED LYMPHOPROLIFERATION: A LYSA ANALYSIS OF THE FRENCH COHORT DESCAR-T

Abstract

Introduction: Post-transplant lymphoproliferative disorder (PTLD) is a rare but severe complication of solid organ transplantation (SOT). First-line treatment typically involves reducing immunosuppressive drugs (ID) alongside Rituximab, followed by maintenance for partial responders (PR) or immunochemotherapy for progression disease (PD). The management of refractory/relapsed (R/R) remains uncertain. The role of CD19 CAR-T cells is not established, though case reports and a series of 22 patients have been published.

Methods: We conducted a retrospective analysis of the multicenter French DESCAR-T registry (NCT04328298) to identify patients treated by CD19 CAR-T cells for SOT-related PTLD. The study period spanned from July 2019 to September 2024. Survival analyses were performed using Kaplan-Meier models.

Results: We identified 12 patients (5 males) treated by CD19 CAR-T cells. Prior SOTs included kidneys (n = 10), liver (n = 1) and lungs (n = 1). In all but one patient, lymphoproliferation occurred more than one year after SOT. All PTLD were classified as diffuse large B cell lymphoma (EBV-associated in 10/11, 1 not available (NA)), except one diagnosed as transformed marginal zone lymphoma. CAR-T cells were administered as second line treatment in 3 patients, and beyond second line in 9 patients. The median age at infusion was 41 years (IQR: 22–62). At diagnosis, performance status was 0-1 in 11/12, Ann-Arbor stage was III-IV in 8/12 and aaIPI score was 1-2 in 11/12 patients. The median lymphocyte rate at apheresis was 0.6G/L (IQR:0-3.4). CAR-T products used included axicabtagene ciloleucel (n = 9) and tisagenlecleucel (n = 3). Ten patients received cyclophosphamide-fludarabine as conditioning regimen (2 NA). ID was modified in all patients at diagnosis then before apheresis. At CAR-T infusion, patients were receiving corticosteroids alone (n = 8), m-TOR inhibitor (n = 1), corticosteroids and calcineurin inhibitor (n = 1), or no ID (n = 2). Cytokine-release-syndrome occurred in all patients with grade 3–4 in 2 cases. Immune-effector-cell associated neurotoxicity (ICANS) was observed in 7 patients with grade 3–4 in 2 cases. Hypogammaglobulinemia (< 5 g/L) was reported in 70% of patients (7/10) without need of immunoglobulins replacement. The best ORR was 82%, including 64% complete response, 18% PR and 18% PD. With a median follow-up of 12.9 months (mo) (95% CI: 4.5-(-)), median progression-free-survival and overall survival were both 16.6 mo (95% CI: 1.1-(-) and 2-(-), respectively) (Figure). Six patients died among which three due to PD and 2 from high grade ICANS (one acute, one late) (1 NA). Among the six surviving patients, one experienced kidney rejection requiring a return to dialysis.

Conclusion: This is the second reported series of patients with R/R SOT-related PTLD treated with CD19 CAR-T cells. Our findings suggest that CD19 CAR-T cell therapy is a feasible option for patients with late R/R PTLD, with manageable toxicity.

Keywords: other; aggressive B-cell non-Hodgkin lymphoma; cellular therapies

Potential sources of conflict of interest:

R. Di blasi

Employment or leadership position: Kite/Gilead: Scientific Advisory Board, Conference speaker, Travel accommodation

Consultant or advisory role: BMS: Scientific Advisory Board

Stock ownership: Janssen: Scientific Advisory Board

Educational grants: Abbvie: Conference speaker

Other remuneration: Novartis: Scientific Advisory Board and Conference speaker