Head to head comparison of on-site produced CD19 Chimeric Antigen Receptor (CAR) T cells in ALL and NHL patients

Orit Itzhaki ¹ Elad Jacoby ^1,2,5 Abraham Nissani ¹ Adva Kubi ¹ Michal Levi ¹ Karin Brezinger-Dayan ¹ Hadar Breier ¹ Li-at Zeltzer ¹ Meir Rosenbaum ^2,5 Amilia Meir ² Arnon Nagler ^3,5 Gal Markel ^1,4 Amos Toren ² Avigdor Abraham ^3,5 Jacob Schachter ¹ Michal J Besser ^1,4

¹Ella Lemelbaum Institute of Immuno- Oncology, Sheba Medical Center, Israel
²Division of Pediatric Hematology and Oncology, The Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Israel
³Division of Hematology and Bone Marrow Transplantation, Sheba Medical Center, Israel
⁴Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Israel
⁵Sackler Faculty of Medicine, Tel Aviv University, Israel

CD19 CAR-T cells demonstrate remarkable remission rates in pediatric and adult patients with refractory or relapsed (r/r) Acute Lymphoblastic Leukemia (ALL) and Non-Hodgkin Lymphoma (NHL).

In 2016, we initiated a clinical trial with on-site produced CD19 CAR-T cells with a CD28 co-stimulatory domain. We analyzed, for the first time, differences in production and phenotype between ALL and NHL patients.

Non-cryopreserved CAR-T cells were produced from patients’ PBMC within 9-10 days. 93 patients with r/r ALL (37) and NHL (53) were enrolled under the same study and CAR T were produced in parallel. All patients were heavily pretreated with a median of 3 prior therapies, including stem-cell transplantations. Three patients dropped out from the study due to clinical deterioration (n=2) or production failure (n=1). 100% of ALL patients and 94% of NHL patients received the target dose of 1x10e6 CAR-T/kg. Cells of ALL patients expanded significantly better and contained more CAR-T cells than of NHL patients. The infusion products from ALL patients contained significantly more naïve CAR-T cells and a significantly higher expression of the chemokine receptor CXCR3. PD-1, LAG-3, TIM-3 and CD28 were equally expressed. The overall response rate was 84% (30/36) in ALL and 62% (32/52) in NHL.

In conclusion, the onsite-production of CAR-T cells is highly efficient and fast. The clinical response rate was high. CAR-T cells can be successfully produced in 99% of patients in just 9-10 days. Cells from ALL patients demonstrate a higher proliferation rate and higher frequencies of CAR-T cells and naïve T cells.