GC-01. Anti-CD19 CAR T-cell therapy in Belarus: Current state
Elena S. Lukojko1, Alexandr A. Migas1, Tatsiana V. Shman1, Igor N. Severin2, Olga A. Kalenik2, Natalya N. Konoplia2, Inna V. Proleskovskaya1, Olga V. Aleinikova3
1 Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, Minsk, Republic of Belarus
2 N. N. Alexandrov National Cancer Center of Belarus, Minsk, Republic of Belarus
3 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia
Contact: Dr. Elena S. Lukojko, e-mail: lenalukojko@gmail.com
Summary
Chimeric antigen receptor (CAR) T-cell therapy has been actively introduced into clinical practice in Belarusian specialized healthcare institutions since 2020 as a part of research protocol NCT05333302. The main objective of given research protocol is safety and efficiency evaluation of locally manufactured CAR T-cell product in the treatment of CD19-positive relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) and lymphoma.
Materials and methods
Manufacture and clinical application of CAR T-cell product was performed at N. N. Alexandrov National Cancer Center of Belarus and in Belarusian Research Center for Pediatric Oncology, Hematology and Immunology. Populations of CD4 and CD8 T-cells were obtained by separate procedures from the apheresis product by immunomagnetic selection. Genetic modification of T-cells was performed by lentiviral transduction with bicistronic vector FMC63-41BB-3z-P2A-hEGFRt coding for second generation CAR and truncated variant of human epidermal growth factor receptor (hEGFRt). After ex vivo cell expansion for 12-14 days, the final CAR T-cell product underwent quality control including sterility check, immunophenotyping and functional activity testing. Pre-conditioning regimen of lymphodepleting chemotherapy included fludarabine and cyclophosphamide. Dose of infused CAR T-cells was in the range of 1-3×106 cells per kilogram of body weight depending on tumor burden. Treatment of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) included tocilizumab and corticosteroids.
Results
CAR T-cell therapy was carried out for 13 patients. CAR T-cells expansion in vivo observed in 12 patients with median peak value 17 (range 1.7-224) cells/mcL of peripheral blood (PB). Median persistence of CAR T-cells in PB of recipients was 60 days (range 13-90). B-cell aplasia was observed in all patients with proven expansion of CAR T-cells. CRS events were confirmed in 77% of cases: grade 1, 7 patients; grade 2 CRS was seen in 1 case; grade 3, in 2 patients. ICANS developed in 46% of cases: grade 1, in 5 patients; grade 3, in 1 case. Complete response (CR) was detected in 6 out of 8 cases with B-ALL. One patient did not respond and died due to disease progression. One more patient died due to complications (CRS + sepsis) not achieving clinical response. Three out of six patients with CR subsequently developed relapse after 4, 5 and 18 months correspondingly. Median remission duration in given group was 9 months (range 4-18). CR was detected in 3 out of 5 patients with B-cell lymphomas, partial response (PR) in 1 case and 1 patient died due to complications (CRS + sepsis) not achieving clinical response. Patients with CR are in remission for 1, 6 and 10 months correspondingly. Patient with PR is preparing for autologous hematopoietic stem cell transplantation. Outcome: of 13 treated patients 9 are alive, 4 patients are dead, median duration of observation was 6 months (range 1-20).
Conclusion
The CAR-T cell technique is safe, reproducible and effective upon current follow-up of ALL patients.
Keywords
CAR Т-cell therapy, B-ALL, B-cell lymphoma.
