CAR-T therapy in solid organ transplant recipients with treatment refractory posttransplant lymphoproliferative disorder

Abstract

Chimeric antigen receptor T cells (CAR‐T) are genetically modified T cells with a chimeric antigen receptor directed against a specific tumor‐associated antigen like CD19 in lymphoma. CAR‐T cells have shown encouraging activity against recurrent and refractory diffuse large B cell lymphomas (DLBCL). However concurrent use of immunosuppressive agents was prohibited in most CAR‐T trials effectively excluding patients with prior solid organ transplantation (SOT) and posttransplant lymphoproliferative disorders (PTLD). We report the outcomes for three patients with PTLD refractory to immunochemotherapy 10‐20 years after SOT who received CAR‐T therapy between January 2018 and December 2019. One patient had an orthotopic heart transplant, the second had a deceased donor kidney transplant, and the third had a pancreas after kidney transplant (PAK). All patients developed complications of CAR‐T therapy such as cytokine release syndrome, immune effector cell‐associated neurotoxicity syndrome, and acute kidney injury requiring renal replacement therapy in the two out of three patients. All patients expired after withdrawal of care due to lack of response to CAR‐T therapy. In addition, the PAK patient developed acute pancreatitis after CAR‐T therapy. This case series identifies the challenges of using CAR‐T therapy to manage refractory PTLD in SOT recipients and its possible complications.

Case Report: Successful Chimeric Antigen Receptor T Cell Therapy in Haploidentical-Allogeneic Stem Cell Transplant Patients With Post-Transplant Lymphoproliferative Disorder

“…To our knowledge, this is the first report of successful chimeric antigen receptor T cell therapy in haploidentical-allogeneic stem cell transplant patients with PTLD. Both patients achieved complete remission after receiving donor-derived CAR-T cell infusions, which was different from the cases previously reported that refractory EBV-negative PTLD in three solid organ recipients did not respond to CAR-T therapy, possibly due to different pathogeneses of EBV-positive and EBV-negative cases ( 18 ).…”

Successful Treatment of Pediatric Refractory Burkitt Lymphoma PTLD after Liver Transplantation using Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy

“…Thus, one could hypothesize that similar results might be obtained in the setting of BL-PTLD. Although there was one trial that reported poor response and death outcomes for three patients with diffuse large B cell lymphomas (DLBCL) PTLD after heart and kidney transplant received CAR T-cell therapy 16 . In one case of an adult patient with refractory BL, a complete response was achieved with anti-CD19 CAR T-cells 17 .…”

Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review

“…All patients experienced significant immunologic side effects, and none showed a response to the treatment. 71 We strongly recommend the use of these treatments only in prospective clinical trials.…”