Rate of durable complete response in ALL, NHL, and CLL after immunotherapy with optimized lymphodepletion and defined composition CD19 CAR-T cells.

102Background: We are conducting a phase I/II trial in which patients (pts) with relapsed or refractory (R/R) CD19+ B cell malignancies receive CD19 CAR-T cells comprised of a defined ratio of CD8+ and CD4+ CAR-T cells. Methods: Pts received lymphodepleting chemotherapy followed by infusion of a 1:1 ratio of CD8+:CD4+ CAR-T cells at one of 3 dose levels (2x105 to 2x107 CAR-T cells/kg). No pts were excluded due to lymphopenia (ALC < 0.5 in 22% of pts), circulating tumor or poor in vitro T cell proliferation. Results: Ninety pts with ALL (n = 36), NHL (n = 41) or CLL (n = 13) received CAR-T cells. Thirty-one of 33 ALL pts (94%) that have had restaging achieved CR by marrow flow cytometry. Two of 31 pts had molecular MRD. In vivo CAR-T cell expansion and persistence, and DFS were superior in pts who received cyclophosphamide (Cy) and fludarabine (Flu) lymphodepletion compared to those who received Cy without Flu. CAR-T cell persistence was limited in patients not receiving Flu by immune responses to the muri...