Outcomes following CD22 CAR T-cells in B-ALL: a tale of two manufacturing strategies.

Abstract

As use of chimeric antigen receptor (CAR) T-cells continues to grow, there is increasing interest in utilizing automated manufacturing systems as a mechanism to support decentralized manufacturing and increase access. However, most FDA approved CAR T-cell therapies are manufactured using traditional bag culture methodologies. Thus, understanding how different manufacturing platforms may impact outcomes is imperative. With parallel trials of CD22 CAR T-cells conducted in patients with B-cell acute lymphoblastic leukemia using a uniform vector but two different manufacturing strategies - either bag-culture (BC) or Prodigy - we were able to compare outcomes. Across 57 patients, 41 received BC cells and 16 received Prodigy-based cells. No significant differences in response rates or incidence of CAR-associated toxicities were observed between cohorts, although the BC cohort had slightly higher rates of severe CRS and IEC-HS. Peak ferritin and C-reactive protein levels were higher in the BC cohort. CAR T-cell expansion was similar, except for patients who had extramedullary disease with low bone marrow disease burden (n = 6 from each group), for whom BC-manufactured cells had greater expansion. In summary, while efficacy across both platforms was comparable, lower inflammatory markers in those who received Prodigy manufactured CAR T-cells suggest changes in the infusion product.