[Modern systemic treatment-bispecific antibodies and CAR-T cell therapy : Clinical management, mechanisms of action, outcomes].

Abstract

Background: Despite chemoimmunotherapy and autologous stem cell transplants, 30-40% of all patients with aggressive B‑cell non-Hodgkin lymphoma relapse.

Objective: The use of targeted therapies is necessary to optimize the survival of these patients.

Results: Chimeric antigen receptor (CAR) T‑cell therapies directed against CD19 are increasingly changing the therapeutic landscape for patients with diffuse large B‑cell lymphoma (DLBCL) and other B‑cell non-Hodgkin lymphomas. Follow-up data show that 30-40% of patients with relapsed or refractory aggressive lymphomas remain disease-free and can be cured in the long term after CAR-T cell therapy. Increasingly improved management of side effects, e.g., cytokine release syndrome (CRS) and neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS), by trained teams improves treatment safety. Bispecific antibodies are also targeted therapies that bind and activate CD3 effector T‑cells and assemble them into B‑cell antigens in the sense of an immunological synapse, resulting in cell-dependent cytotoxicity. Some of these drugs are also approved for aggressive and some for indolent B‑cell non-Hodgkin lymphoma; they are available off the shelf and can also be used in particular for older and less fit patients.

Conclusion: Both treatment options have significantly improved the prognosis of patients with lymphoma and generally have lower toxicities.