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Purpose: UCART19 is an “off-the-shelf” genome-edited anti-CD19 CAR-T cell product, manufactured from unrelated healthy donor cells. Patients and Methods: UCART19 was administered to 25 adult patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) in the CALM trial. All patients underwent lymphodepletion with fludarabine and cyclophosphamide ± alemtuzumab and received one of three ascending doses of UCART19. Given the allogeneic nature of UCART19, we analyzed the impact of lymphodepletion, HLA disparities and host immune system reconstitution on its kinetics, along with other factors known to affect autologous CAR-T cell clinical pharmacology. Results: Responder patients (12/25) had higher UCART19 expansion (Cmax) and exposure (AUCTlast) than non-responders (13/25), as measured by transgene levels in peripheral blood. The persistence of CAR+ T cells didn’t exceed 28 days in 10/25 patients and lasted beyond 42 days in 4/25. No significant correlation was found between UCART19 kinetics and administered cell dose, patient and product characteristics or HLA disparities. However, the number of prior lines of therapy and absence of alemtuzumab negatively impacted UCART19 expansion and persistence. Alemtuzumab exposure positively affected interleukin-7 and UCART19 kinetics, while negatively correlating with host T-lymphocyte AUC0-28. Conclusions: UCART19 expansion is a driver of response in adult R/R B-ALL patients. These results shed light on the factors associated with UCART19 kinetics, which remain highly affected by the impact of alemtuzumab on interleukin-7 and host-versus-graft rejection.

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