CAR-T for management of R/R PTLD following lung transplant: A multi-center retrospective study

Post-transplant lymphoproliferative disorder (PTLD) is a rare malignancy following solid organ transplantation (SOT), with lung transplant recipients experiencing disproportionately high rates of progression and mortality. While CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated efficacy in relapsed/refractory (R/R) B-cell lymphoma, its role in PTLD remains underexplored, particularly in lung SOT. We present a multi-center retrospective study of three lung transplant recipients treated with Axicabtagene ciloleucel (Axicel) for R/R PTLD. All patients had received multiple lines of prior therapy, including chemoimmunotherapy, with one patient also receiving EBV-specific T-cell therapy (Tabelecleucel). CAR-T therapy resulted in complete or partial response in all three patients, although one subsequently developed allograft rejection. Immunosuppression (IST) was held at the time of lymphodepletion and re-introduced variably post-CAR-T depending on risk of rejection versus risk of relapse/recurrence. Cytokine release syndrome (CRS) was observed in all cases but was mild, occurred early post-CAR-T, and managed effectively with tocilizumab with/without dexamethasone Our study highlights the feasibility of CAR-T therapy in lung SOT recipients with PTLD, with promising responses and manageable toxicities. Individualized and judicious modification of IST around CAR-T infusion is critical to balance efficacy and disease relapse with lung allograft preservation. These cases highlight the limitations of current CAR-T studies, which have excluded this high-risk, immunologically complex patient population, and underscore the need for further publications in this patient subset to better understand how to manage IST around CAR-T.