Hematopoietic recovery and immune reconstitution after axicabtagene ciloleucel in patients with large B-cell lymphoma.
Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 may be associated with long-term adverse effects such as cytopenia and immune deficiency. To characterize these late events, we analyzed 31 patients with relapsed or refractory large B-cell lymphoma treated with axicabtagene ciloleucel at our institution on 2 clinical trials, ZUMA-1 (NCT02348216) and ZUMA-9 (NCT03153462). Complete blood counts, lymphocyte subsets, and immunoglobulin levels were measured serially until month 24 or progression. Fifteen (48%) patients had grade 3-4 cytopenia, anemia (5 [16%]), neutropenia (9 [29%]), or thrombocytopenia (13 [42%]) at day 30. Cytopenia at day 30 was not significantly associated with later diagnosis of myelodysplasia. Among patients with ongoing remission, grade 3-4 cytopenias was observed in 1/9 (11%) at 2 years. While peripheral CD8+ T cells recovered early, CD4+ T cell recovery was delayed with a count of <200/μL in 3/9 (33%) patients at 1 year and 2/7 (29%) at 2 years. Immunoglobulin G levels normalized in 5/9 (56%) patients at 2 years. Thirteen (42%) patients developed grade 3-4 infectious complications, including herpes zoster and Pneumocystis jiroveci pneumonia. These results suggest the need for prolonged monitoring and prophylaxis against opportunistic infections in these patients to improve the long-term safety of axicabtagene ciloleucel therapy.