LP-08. Experience with CAR-T-cell therapy in the treatment of indolent and aggressive lymphomas

Summary

CAR-T-therapy (Chimeric antigen receptor T cells), according to world experience, is one of the promising methods for the treatment of relapsed/refractory cases of hemoblastoses, which allows achieving long-term remissions with minimal toxicity. The experience of conducting CAR-T therapy in the Russian Federation is minimal. This study brings together data regarding the use of CAR-T therapy in the treatment of B/T-cell lymphomas as a third and subsequent line of therapy. Our aim was to evaluate efficiency of CAR-T therapy in the treatment of patients with indolent and aggressive B/T-cell lymphomas.

Materials and methods

A prospective study was conducted from 2017 to 2023 at the Department of Chemotherapy for Lymphatic Tumors (National Research Center for Hematology, Moscow) with bone marrow and hematopoietic blood stem cell transplantation Unit and a day Hospital. The study group included 19 patients with recurrent/refractory hemoblastoses (n=4, primary mediastinal large B-cell lymphoma, PMBCL; n=3, mediastinal gray zone lymphoma, MGZL; n=3, follicular lymphoma, FL; n=4, FL with transformation to DLBCL; n=2, angioimmunoblastic lymphoma, AIBL; n=1, DLBCL; n=1, Hodgkin’s lymphoma; HL), who underwent CAR-T- therapy as a third/subsequent line of therapy, including patients after auto-HSCT (2/19, 11%)). The median age was 45 (21-76) years. Leukapheresis, production and introduction of CAR-T cells were performed in four clinics: “N. N. Aleksandrov Republican Scientific and Practical Center of Oncology and Medical Radiology” (Republic of Belarus), Department of Research and Development, Geno-Immue Medical Institute (Shenzhen, China), Sheba Governmental Hospital (Israel), University Hospital of Giessen and Marburg (Germany). CAR-T cells were used with two- or three-lineage orientation in 13/19 (68%) cases, with uni-linear orientation, in 6/19 (32%) cases. Statistical analysis, in addition to the standard descriptive one, included the Kaplan-Meier method to plot survival curves. The statistical differences were assessed with a logarithmic rank test. P values <0.05 were considered significant.

Results

Among 19 patients who received CAR-T therapy, the antitumor response was evaluated in 17 cases (two patients still are in the course of treatment). The overall antitumor response was obtained in 24% of cases (4/17), who achieved complete remission of the disease, i.e., in patients with FL (n=2), FL with transformation to DLBCL (n=1), and DLBCL (n=1). In 9 of 13 cases with tumor progression after CAR-T therapy, the mortality rate was 69% including all four patients with a TP53 gene mutation. Four patients (31%, 4 of 13 cases) after CAR-T therapy received non-programmed regimens of therapy with complete remission achieved, i.g., nivolumab-lenalidomide (n=2, MGZL), polatuzumab vedotin-bendamustine (n=1, FL with transformation in DLBCL), nivolumab monotherapy (n=1, AIBL). The median follow-up was 9 months (since injection of CAR-T cells).

Conclusion

CAR-T therapy as a “rescue therapy” in the third and subsequent lines of therapy for hemoblastoses is effective only in 24% of cases, and is not effective in patients with a mutation in the TP53 gene. Our results suggest a need for optimized treatment protocols by inclusion of targeted drugs into the first-line therapy, and implementation of CAR-T therapy at earlier stages of treatment.

Keywords

Non-Hodgkin’s lymphoma, refractoriness, CAR-T therapy.