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Chimeric antigen receptor T-cell therapy in adult patients with B-cell lymphoproliferative diseases

https://doi.org/10.35754/0234-5730-2022-67-1-8-28

Abstract

Introduction. The introduction of chimeric antigen receptor (CAR) T-cell therapy is a promising treatment of patients with relapsed or refractory (R/R) B-cell lymphoproliferative diseases (LPDs).

Aim — to present the results of CAR-T-cell therapy of 6 adult patients with B-cell LPDs.

Materials and methods. This is a pilot study conducted in adult patients with R/R or persistent minimal residual disease B-cell LPDs treated with CAR-T-cells. The study was approved by a local ethical committee of National Research Center for Hematology. Patients did not have alternative options for effective and safe treatment. All patients signed an informed consent. All patients were lymphodeplated with fl udarabine and cyclophosphamide for 4 days before the introduction of CAR-T-lymphocytes. Cytokine release syndrome (CRS) was prevented by tocilizumab on the day of CAR-T-cell administration. The effi cacy and safety of CAR-T-cell therapy was evaluated.

Results. From 01.01.2020 to 01.01.2022, 10 CAR-T-cell infusions were performed for 6 adult patients (age 19–68 years, median — 32 years) with B-cell LPDs: 4 — R/R B-acute lymphoblastic leukemia, 1 — R/R diffuse large B-cell lymphoma, 1 — persistence of MRD in mantle cell lymphoma. In all patients with a R/R, median — 4 (2–5) lines of chemotherapy and/ or immunotherapy were performed before CAR-T-cell therapy. CD19 CAR-T-cells received 3 patients, CD19/CD22 CAR-Tcells — 2 patients, CD19 and CD20 CAR-T-cells received 1 patient. Autologous CAR-T-cells received 4 (66 %) patients, allogeneic CAR-T-cells received 1 patient, and one patient had two CAR-T-cell administrations — 1 autologous and 1 allogeneic. The median number of CAR-T-cells was 0.5 × 106 /kg (from 0.1 × 106 /kg to 3 × 106 /kg). In 7 (87.5 %) of the 8 cases after CAR-T-cell administration, overall response to therapy (complete or partial remission) was achieved, and complete remission was achieved in 6 (75 %) cases. Side effects were noted after 8 of 10 CAR-T-cell transfusions: CRS in 40 % (CRS 1 — 10 %, CRS 2 — 20 %, CRS 3 — 10 %), ICANS in 10 %, tumor lysis syndrome in 20 %, multi-organ dysfunction syndrome in 10 %.  There were no lethal complications due to CAR-T-cell administrations. The median follow-up period was 6 (1–16) months. Of the 6 patients, 2 (33 %) died from relapses and progression of LPD. One (17 %) patient died in complete remission from infectious complications. Three (50 %) patients are observed till now. The median time of CAR-T-cell circulation was 33 (6– 60) days.

Conclusion. CAR-T-cell therapy is a promising treatment for R/R B-cell LPDs and LPDs with persistence of MRD after cytoreductive therapy. This type of therapy requires a multidisciplinary approach.

About the Authors

O. A. Gavrilina
National Research Center for Hematology
Russian Federation

Olga A. Gavrilina, Cand. Sci. (Med.), Head of the Observational Department 

125167, Moscow



G. M. Galstyan
National Research Center for Hematology
Russian Federation

Gennadiy M. Galstyan, Dr. Sci. (Med.), Head of the Department of Resuscitation and Intensive Care 

125167, Moscow



A. E. Shchekina
National Research Center for Hematology
Russian Federation

Antonina E. Shchekina, Postgraduate Student, Physician, Resuscitation and Intensive Care Unit 

125167, Moscow



E. S. Kotova
National Research Center for Hematology
Russian Federation

Ekaterina S. Kotova, Postgraduate Researcher, Department of Intensive HighDose Chemotherary of Haemoblastosis and Hametopoiesis Depressions 

125167, Moscow



M. A. Maschan
Dmitriy Rogachev Nation al Medical Research Center of Pediatric Hematology, Oncology and Immunology
Russian Federation

Michail M. Maschan, Dr. Sci. (Med.), Deputy Director, Director of the Institute of Molecular and Experimental Medicine 

117997, Moscow



V. V. Troitskaya
National Research Center for Hematology
Russian Federation

Vera V. Troitskaya, Cand. Sci. (Med.), Deputy Director General for Medicine 

125167, Moscow



D. A. Koroleva
National Research Center for Hematology
Russian Federation

Daria A. Koroleva, Cand. Sci. (Med.), Hematologist, Department of Intensive High-dose Chemotherapy of Lymphomas 

125167, Moscow



E. E. Zvonkov
National Research Center for Hematology
Russian Federation

Evgeny E. Zvonkov, Dr. Sci. (Med.), Head of the Department of Intensive Highdose Chemotherapy of Lymphomas 

125167, Moscow



Z. T. Fidarova
National Research Center for Hematology
Russian Federation

Zalina T. Fidarova, Cand. Sci. (Med.), Head of the Department of Intensive High-Dose Chemotherary of Haemoblastosis and Hametopoiesis Depressions  

125167, Moscow



V. A. Vasilyeva
National Research Center for Hematology
Russian Federation

Vera A. Vasilyeva, Cand. Sci. (Med.), Head of Immunochemotherapy Department for Patients after BMT, National Research Center for Hematology 

125167, Moscow



E. N. Parovichnikova
National Research Center for Hematology
Russian Federation

Elena N. Parovichnikova, Dr. Sci. (Med.), CEO of the National Research Center for Hematology 

125167, Moscow



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Gavrilina O.A., Galstyan G.M., Shchekina A.E., Kotova E.S., Maschan M.A., Troitskaya V.V., Koroleva D.A., Zvonkov E.E., Fidarova Z.T., Vasilyeva V.A., Parovichnikova E.N. Chimeric antigen receptor T-cell therapy in adult patients with B-cell lymphoproliferative diseases. Russian journal of hematology and transfusiology. 2022;67(1):8-28. (In Russ.) https://doi.org/10.35754/0234-5730-2022-67-1-8-28

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