Онкогематология (Sep 2023)
Use of locally produced anti-CD19 CAR-T cells in the treatment of relapsed/refractory B-cell lymphomas in adults
Abstract
Background. Patients with B-cell lymphoma have an extremely unfavorable prognosis after relapse or in case of refractoriness to the first and consecutive lines of immunochemotherapy with the anti-CD19 CAR-T cells being the only therapeutic option to such patients. the manual preparation of anti-CD19 CAR-T lymphocytes was reproduced in the N. N. Alexandrov republican research and practical center for oncology and medical radiology (Minsk). Their safety was demonstrated. Aim. To estimate safety, tolerability and efficacy of the in-house CAR-T cells, including objective response rate, progression-free and overall survival. Materials and methods. The second generation anti-CD19 chimeric antigen receptor contained an anti-CD19 antibody scFv fragment, CD28 transmembrane domain, 4-1BB and CD3z signaling domains. the coding sequence was cloned into the lentiviral vector S4. The cell product was obtained by expansion of CD4- and CD8-positive lymphocytes populations with IL-7 and IL-15 after initial activation and lentiviral transduction with vector S4. CAR-T cells were infused into 8 patients with refractory forms of B-cell lymphoma after the preliminary lymphodepleting chemotherapy. Persistence of CAR-T cells was assessed by flow cytometry. therapeutic efficiency was assessed by positron emission tomography-computed tomography with 18F-fluorodeoxyglucose. Results. Expansion of CAR-T cells with resulting b-cell aplasia was observed in all patients. the median of observation was 113 days (range 22–529 days). objective response rate was 100 %, complete remission was observed in 6 patients, partial response – in 1 patient. One patient died because of complications before the clinical response. Overall survival was 88 ± 12 %. cytokine release syndrome and neurotoxicity were not observed in 6 out of 8 patients despite a high tumor burden. Conclusion. Our study demonstrated efficiency and safety of the in-house CAR-T cells for the treatment of patients with refractory B-cell lymphomas.
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