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.

• Authors: Sambhavi Krishnamoorthy, Armin Ghobadi, Rowena D Santos, Joel D Schilling, Andrew F Malone, Haris Murad, Nancy L Bartlett, Tarek Alhamad
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 21 Issue 2 Pg. 809-814 (02 2021) ISSN: 1600-6143 [Electronic] United States
• PMID: 33089906 (Publication Type: Journal Article)
• Copyright: © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Receptors, Chimeric Antigen

Topics

• Acute Disease
• Humans
• Lymphoproliferative Disorders (etiology, therapy)
• Organ Transplantation (adverse effects)
• Pancreatitis
• Receptors, Chimeric Antigen