ABSTRACT
The outcome of patients with malignant lymphoma has significantly improved over the last decades. Major contributions have come from an increased knowledge of the disease, from its better classification, and from relevant advances in treatment. Novel important therapies have been added to the existing approach, making it possible to improve direct cancer cell killing. Further, these new therapies also support the immune system to act against the tumor, opening the era of immuno-oncology (IO). In the field of IO, chimeric antigen receptor (CAR)-T-cell therapies represent one new effective approach that has so far produced unprecedented results in the treatment of lymphomas. Four CAR-T products are available to treat relapsed refractory patients with diffuse large B-cell lymphoma (DLBCL), transformed indolent lymphomas, primary mediastinal B-cell lymphomas, and mantle cell lymphomas. Several clinical trials are currently recruiting patients to evaluate the addition of novel indications for CAR-T, to anticipate the use of CAR-T to earlier lines of treatment for DLBCL patients, and to explore combination therapies. Moreover, the CAR approach is investigated using cells other than T lymphocytes to improve feasibility and reduce the toxicity of therapy. In this review we describe the state of the art of clinical research and real-world data on the use of CAR-T, which likely represents a new milestone in the treatment of malignant lymphomas.

IMPACT STATEMENT
Clinical trials and real-world data confirm CAR-T cell therapy as a revolutionary treatment for patients with diffuse large B-cell lymphoma.