Impaired hematopoiesis affects apheresis and CAR T-cell product composition and treatment response.

[BACKGROUND] Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of hematologic malignancies, but its success depends on obtaining sufficient CD3 T-cell yields during leukapheresis. This can be difficult in heavily pretreated patients, who often show leukopenia and reduced T-cell fitness.

[METHODS] We analyzed 166 leukapheresis products from 154 patients undergoing manufacturing of CD19-directed CAR T-cells, including 146 from non-Hodgkin's lymphoma (NHL) and 20 from acute lymphoblastic leukemia (ALL). Collections were performed for commercial CAR T-cell products (axi-cel, tisa-cel, brexu-cel, liso-cel; n = 121) and the HD-CAR-1 trial with in-house manufacturing (heidagenlecleucel; n = 45).

[RESULTS] In 150/154 patients, a sufficient CD3 T-cell yield was achieved by a single leukapheresis. Pre-apheresis lymphocyte count strongly predicted CD3 T-cell yield (p< .001) and was associated with treatment response (p = .044). Impaired hematopoiesis, reflected by reduced nucleated cell count (p< .001), lymphocyte count (p <.001), and hematocrit (p = .017), was linked to poorer collection efficiency. Intensive prior therapies, including stem cell transplantation, reduced CAR T-cell expansion during manufacturing (p = .036). In patients with ALL, higher proportions of effector and CD8 CAR T-cells in the product correlated with improved clinical outcomes (p = .04; p = .023).

[CONCLUSION] These findings highlight the importance of early leukapheresis, ideally before intensive treatments, to optimize T-cell yield, product quality, and therapeutic efficacy.