Immunotherapy of diffuse large B-cell lymphoma


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Abstract

First-line CHOP-R immunochemotherapy provides long-term progression-free survival (PFS) in 33-96% of patients with diffuse large B-cell lymphoma (DLBCL) depending on the prognosis, but progression or relapse occurs in 30-40% of patients. When carrying out high-dose chemotherapy with autologous hematopoietic stem cell transplantation (HDCT with auto-HSCT) for patients with chemo-sen-sitive recurrence of DLBCL, 5-year event-free survival (EFS) reaches 46%, overall survival (OS) - 53%. To improve the results of HDCT with auto-HSCT, new “rescue" therapy regimens are being studied, as well as modes of supporting remission after HDCT with auto-HSCT. The effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with recurrence of DLBCL after HDCT with auto-HSCT was confirmed by high rates of 3-year PFS and OS - 41 and 53%. Modern ideas about the molecular biological characteristics of DLBCL justify the use of immunotherapy in the treatment of relapses and refractory forms. Modern “rescue" therapies for the DLBCL with high efficacy and low toxicity are especially relevant for patients who are not candidates for HDCT with auto-HSCT, as well as for relapses after HDCT with auto-HSCT. In June 2019, the FDA granted accelerated approval for the use of polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of relapses and refractory forms of DLBCL after two or more lines of previous therapy. In June 2018, the FDA granted granted for pembrolizumab in the treatment of adults and children with relapses and refractory forms of primary mediastinal (thymic) B-cell lymphoma (PMBCL) after two or more lines of previous systemic therapy. The antitumor efficacy of the combination of nivolumab with brentuximab vedotin is significantly higher compared to that of monotherapy with nivolumab/pembrolizumab, brentuximab vedotin: the overall response (OR) rates are 73.0%, 48.0 and 13.3%, complete remissions (CR) - 37% , 13, 0% in PMVCL patients with relapses and refractory forms. In the Phase IIL-MIND study [NCT0239085], the efficacy of tafasitamab (OR - 60%, CR - 43%) is comparable to that of CAR-Tcell therapy in patients with relapses and refractory forms of DLBCL, while tafasitamab has significantly lower toxicity. In order to increase the antitumor effect of immunotherapy, combined modes are being studied, primarily with various mechanisms of action and possible synergistic antitumor activity. The identification of predictive biomarkers will allow to develop an optimal algorithm for the appointment of immunotherapy, which helps to determine the dose, regimen, effectiveness and duration of therapy. Promising areas of DLBCL therapy are associated with the further study of new targets for tumor cells and their signaling pathways.

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About the authors

L. V Filatova

N.N. Petrov National Medical Research Center of Oncology;North-Western State Medical University n.a. I.I. Mechnikov

Email: Larisa_Filatova@list.ru
Dr. Sci. (Med.), Leading Researcher at the Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation, N.N. Petrov National Medical Research Center of Oncology; Professor at the Department of Oncology, North-Western Medical University n.a. I.I. Mechnikov 68, Leningradskaya str., Pesochny settlement, St. Petersburg 197758, Russian Federation

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