Relapsed/Refractory Non-Hodgkin Lymphoma: Engineering T-Cells to Express Chimeric Antigen Receptors (CARs), a Salvage?

Abstract

For years, patients with B-cell non-Hodgkin lymphoma (NHL) have been treated with traditional first-line therapies with a fairly acceptable outcome. However, some individuals with relapsed or resistant lymphoma do not respond to those treatments, including chemotherapy, immunotherapy, radiotherapy, and (or) autologous stem cell transplantation. Based on the acquired immunotherapy knowledge, T-cells genetically engineered with chimeric antigen receptors (CARs) seem to offer complete, enduring clinical responses to patients with refractory or relapsed lymphomas. Currently, four autologous CD19-directed CAR T-cell therapies have gained approval by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, highgrade B-cell lymphoma, and transformed follicular lymphoma, while further CAR T-cell immunotherapies have entered the clinical trials pipeline. This review aims to summarize the efficacy and safety of the FDAapproved CAR T-cell treatments for the relapsed or refractory lymphomas.

The emerging role of off-the-shelf engineered natural killer cells in targeted cancer immunotherapy

“…CAR T cells represent a cutting-edge immunotherapeutic approach that has revolutionized cancer treatment. Currently, the U.S. Food and Drug Administration (FDA) has approved four autologous CD19-directed CAR T cell therapies for the treatment of relapsed or refractory diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, high-grade B cell lymphoma, and transformed follicular lymphoma, 49 as well as one autologous B cell maturation antigen (BCMA)-directed CAR T cell therapy for the treatment of relapsed/refractory MM. 50 Despite the successes of CAR T cell therapy in the clinic, several challenges remain unaddressed.…”

Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently

“…CAR received impressive remissions, with complete remission (CR) rate 81% (Roex et al, 2020). Compared with favorable results in ALL, the therapeutic effect of CD19 CAR-T in CLL and NHL was dissatisfactory (Kanwal, 2021;Mancikova and Smida, 2021;Myers et al, 2021;Yin et al, 2021). Food and Drug Administration (FDA) approved four autologous CD19-directed CAR-T cell treatments for R/R lymphoma (Ti et al, 2020).…”

“…Overall response rate (ORR) ranged from 53.1% to 87%, with CR rates ranging from 39.5% to 62%. Meanwhile, grade 3 or higher cytokine release syndrome (CRS) occurred in 10% to 46% of the individuals (Kanwal, 2021). On-target effects caused by CAR-T cell binding cause CRS, which is a series of hazardous side effects (Cosenza et al, 2021).…”