CD19 CAR T-cell (BY19) therapy for Pediatric and Adult Patients with Relapsed or Refractory B-Cell Neoplasms in Belarus: Phase 1 trial

Despite the approval of multiple CAR T-cell products, access to this therapy remains limited in many developing countries. We conducted a single-arm, open-label, non-randomized, parallel phase 1/2 clinical trial (ClinicalTrials.gov identifier: NCT05333302) at two independent centers: the Vitebsk Regional Clinical Cancer Centre (VRCCC) and the Belarusian Research Center for Pediatric Oncology, Hematology, and Immunology (BRC POHI). The study enrolled patients with relapsed or refractory B-cell malignancies who received an in-house manufactured CD19 CAR T-cell product (BY19) following lymphodepletion with either fludarabine plus cyclophosphamide or cyclophosphamide plus fludarabine and decitabine. Seven patients at VRCCC and sixteen at BRC POHI received CD19 CAR T-cell therapy, comprising 17 patients with B-ALL, one with chronic lymphocytic leukemia (CLL), and five with non-Hodgkin lymphoma. The median age was 45 years (range: 38-56) at VRCCC and 13.5 years (range: 4-30) at BRC POHI. Cytokine release syndrome (CRS) occurred in 18 (67%) of the 27 infusions across both centers, predominantly mild cases. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 12 (44%) patients, with severe ICANS (grade [≥]3) in 5 patients (18.5%). The overall response rate (ORR) was 80.0% (16/20), with a complete response (CR) rate of 75.0% (15/20) at the first assessment on day 28. The median progression-free survival (PFS) was 23 months, and the median overall survival (OS) was 55 months. At 12 months, PFS was 83.3% for non-Hodgkin lymphoma patients and 48.3% for B-ALL patients. Higher Cmax levels tended to correlate with better response rates; however, no clear advantage in PFS was observed. In conclusion, our in-house manufactured CD19 CAR T-cell product (BY19) demonstrates a safety and efficacy profile comparable to approved CD19 CAR T-cell therapies. This study underscores the translational potential of localized CAR T-cell manufacturing to expand global access to advanced immunotherapies, especially in middle-income countries. Additionally, incorporating decitabine into the lymphodepletion regimen shows promise in enhancing therapeutic efficacy and warrants further prospective investigation.