CAR-T cell therapy in Israel – Clinical results of the first 90 patients treated with on-side produced CD19 CAR T cells

Introduction

Autologous CD19 chimeric antigen receptor (CAR) T cells demonstrate outstanding remission rates in pediatric and adult patients with relapsed and refractory acute lymphoblastic leukemia (ALL) and Non-Hodgkin lymphoma (NHL). Two CD19 CAR T cell products received recently FDA approval.

Patients and method

In October 2017, the Sheba Medical Center initiated the first phase 1b/2 study with on-site produced CD19 CAR T cells in Israel. Gamma-retrovirus encoding for a CD19 CAR based on an FMC63 derived scFv, CD28 costimulatory domain and CD3-zeta signaling domain was used for the study. CAR-T cells were produced from patients’ PBMC within 9-10 days.

Results and discussion

Until June 2019, 95 patients (half ALL and half NHL) were enrolled to the trial and 90 (95%) patients were treated. CAR T cells were successfully produced for 94 of 95 (99%) patients. Four patients dropped out of the study due to clinical deterioration. The median age of patients was 34 years (range 22 months – 71 years). Patients had a median of 4 prior regimens, including other CD19-based therapies and stem-cell transplantations. The overall response rate of evaluated patients was 70% (81% in ALL and 56% in NHL), including complete remission in 53%. The 1-year overall survival was 61%.

Conclusion

The clinical response rate and overall survival in refractory patients treated with on-site produced CAR T is remarkable and comparable with commercial CAR T products. The extremely fast turn-around time from PBMC collection to CAR T infusion of only 9-10 days, in contrast to 30-60 days with commercial CAR T products, and the high production success (99%) enabled the treatment of 95% of enrolled patients. We are currently aiming to transfer the production process into an automated system and make the therapy available to even more patients.