Potential of small-molecule targeted drugs in combination with CAR-T cell therapy for hematologic lymphomas

As the traditional first-line standard treatment of B-cell non-Hodgkin's lymphoma, the R-CHOP chemotherapy regimen faces the problem of about 30%-40% of patients progressing into relapsed or refractory disease. Small molecule targeted drugs and CAR-T cell therapy, represented by BTK inhibitors and Bcl-2 inhibitors have achieved breakthrough results in the treatment of lymphoma, but they still face restrictions such as limited single-drug efficacy, drug-resistant recurrence, and toxic reactions. In order to overcome the shortcomings of single therapy, combined treatment strategies have become a research hotspot. This review systematically summarizes the efficacy evidence of the current preclinical and early clinical combined treatment of small molecule targeted drugs and CAR-T cell therapy. The potential synergistic mechanism of the joint application of small molecule targeted drugs and CAR-T cell therapy is discussed, including improving the tumor microenvironment, enhancing the function of CAR-T cells, improving the sensitivity of tumor cells to CAR-T, inhibiting exhaustion, and reducing toxicity. This joint strategy is expected to improve the therapeutic effect and overcome drug resistance. It is a very promising development direction for the treatment of relapsed or refractory lymphoma in the future. At the same time, further in-depth research is needed to promote its clinical transformation and application.