Impact of blinatumomab and inotuzumab exposure on apheresis composition for CAR T in patients with B-cell acute lymphoblastic leukemia.

Children with B-cell acute lymphoblastic leukemia (B-ALL) are increasingly treated with immunotherapeutic agents such as blinatumomab and inotuzumab. Thus, those who present in relapse for chimeric antigen receptor (CAR) T-cell therapy are likely to have prior exposure to these other immunotherapies. The effect of blinatumomab and inotuzumab exposure on cellular therapy, particularly, cell collection and the composition of apheresis products, is unknown. In this study, we analyzed the apheresis composition of 113 pediatric and young adult patients with relapsed or refractory B-cell malignancies across three CAR T-cell trials spanning from 2014 to 2024 and compared patients who did or did not have exposure to blinatumomab or inotuzumab prior to cell collection. We found no association between blinatumomab exposure and differences in apheresis composition, including total nucleated cell (TNC) yield, CD3 counts, CD56 counts, or CD4:CD8 ratio of CD45+ cells. The apheresis products from patients with inotuzumab exposure had lower CD4:CD8 ratios compared to those of patients without inotuzumab exposure. There were no other notable differences in T-cell phenotype or markers of exhaustion among the subset of samples with extended flow cytometry panels. With the exception of lower CD4:CD8 ratios in patients with prior inotuzumab, the comparable apheresis yield and composition observed after immunotherapy exposure is a reassuring finding, particularly in light increased use of upfront blinatumomab for B-ALL.