CD19 CAR T cell therapy BY19 for pediatric and adult patients with relapsed or refractory B cell neoplasms in Belarus: Phase 1 trial.
Access to chimeric antigen receptor (CAR) T cell therapy remains limited in many developing countries. We conducted a single-arm, open-label, phase 1 trial (NCT05333302) at two Belarusian centers, evaluating an in-house manufactured CD19 CAR T cell product (BY19) in pediatric and adult patients with relapsed/refractory B cell malignancies. Lymphodepletion included fludarabine/cyclophosphamide, with or without decitabine. Twenty-three patients received therapy: seventeen B cell acute lymphoblastic leukemia, one chronic lymphocytic leukemia, and five non-Hodgkin lymphomas. Cytokine release syndrome (CRS) occurred in 67% of infusions, mostly grade 1-2, with severe CRS in 19%. Immune effector cell-associated neurotoxicity occurred in 44%, with severe cases in 18.5%. The overall response rate was 80% (16/20 evaluable), with complete remission achieved in 75% at day 28. Median progression-free survival (PFS) was 23 months; 12-month PFS was 83.3% in lymphoma and 48.3% in B cell acute lymphoblastic leukemia (B-ALL). Higher Cmax levels tended to correlate with better response rates (p = 0.0416); however, no clear advantage in PFS was observed. BY19's safety and efficacy profiles were comparable to approved CD19 CAR T cell products. This study underscores the translational potential of localized CAR T cell manufacturing to expand global access to advanced immunotherapies, especially in middle-income countries. Decitabine-containing lymphodepletion showed potential benefit and warrants further study.
Authors
Katsin Katsin, Dormeshkin Dormeshkin, Migas Migas, Karas Karas, Shman Shman, Serada Serada, Khalankova Khalankova, Klych Klych, Lutskovich Lutskovich, Lukoika Lukoika, Meleshko Meleshko
View on Pubmed