Feasibility and safety of CD19 CAR T cell treatment for B-cell lymphoma relapse after allogeneic hematopoietic stem cell transplantation.

Abstract Although CD19-directed chimeric antigen receptor (CAR) T cells have been successfully used after a preceding allogeneic stem cell transplantation (alloHCT) in patients with acute lymphoblastic leukemia, little is known about feasibility and outcome of CAR T cell treatment in patients who have been previously allotransplanted for lymphoma. In a single centre retrospective analysis, course and outcome of all allografted patients who have been treated with CD19 CAR constructs for B-cell lymphoma between October 2018 and November 2019 were studied. CAR therapy consisted either of a third-generation CAR (HD-CAR-1), or of commercially manufactured axicabtagene ciloleucel (axi-cel, Gilead). Altogether 10 CAR T cell dosings using recipient leukapheresis products were performed in 8 patients: 4 patients (2 mantle cell lymphoma, 2 chronic lymphocytic leukemia) received 6 dosings with HD-CAR-1; and 4 patients (all with diffuse large B-cell lymphoma) received 4 dosings with axi-cel. Overall, 6 of 8 (75%) of the patients responded. CAR treatment was well tolerated with grade ≥3 cytokine release syndrome and neurotoxicity each being observed after 1 of 10 dosings. A single patient had moderate chronic GVHD. Of note, three of four patients who received axi-cel had ongoing grade ≥3 cytopenia three months post-dosing, whereas prolonged cytopenia was not observed in 9 alloHCT-naive patients who received axi-cel during the same time period. In conclusion, CAR T cell treatment from recipient-derived leukapheresis products after a prior alloHCT appears feasible, effective, and safe in patients with B-cell lymphoma. Protracted cytopenia after axi-cel treatment is a matter of concern and requires further exploration.