Third-Generation CD19-Directed CAR-T Cell Treatment Shows Promising Efficacy for Patients With R/R ALL

A first report of a phase-1/2 investigator-initiated trial demonstrated that a regimen of escalating doses of third-generation CAR-T cells were associated with favorable clinical efficacy and low procedure-specific toxicity in treating adult patients with acute lymphoblastic leukemia (ALL). 

In this trial, 13 patients were treated with escalating doses of CD19-directed CAR-T cells between 1 × 106 and 50 × 106 CARTs/m². Each step of the treatment, including leukapheresis, manufacturing, and administration of CAR-T cells were performed in-house. End points included feasibility of manufacturing and treatment safety, clinical efficacy, as well as survival.

Upon study completion on day 90 following CAR-Ts, 10 patients were evaluable for response; 8 patients achieved a complete remission (CR), including 5 patients with minimal residual disease (MRD)-negative CR. At 1-year follow-up, the median overall survival (OS) was not reached, while progression-free survival (PFS) was 38%; Median PFS was reached on day 120. It was noted that lack of CD39-expression on memory-like T cells was more frequent in CAR-T products of responders when compared to CAR-T products of non-responders. Following CAR-T administration, higher CD8 + and γδ-T cell frequencies, a physiological pattern of immune cells and lower monocyte counts in the peripheral blood, were associated with response.

For the full patient population, CAR-T manufacturing was noted to be feasible. As for adverse events, no patients developed any grade of immune effector cell-associated neurotoxicity (ICANS) syndrome or a grade 3 or higher cytokine release syndrome (CRS). Additionally, CAR-T expansion and long-term CAR-T persistence were evident in the peripheral blood of evaluable patients.

Study authors concluded, “Third-generation CAR-Ts were associated with promising clinical efficacy and remarkably low procedure-specific toxicity, thereby opening new therapeutic perspectives for patients with [R/R] ALL.”

Source:

Schubert ML, Schmitt A, Hückelhoven-Krauss A. et al. Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. J Hematol Oncol 2023;16, (79). doi:10.1186/s13045-023-01470-0