Anticorps bispécifiques en onco-hématologie

Une révolution en onco-hématologie : les anticorps bispécifiques. L’essentiel à connaître pour les réanimateurs.

Abstract

Bispecific antibodies have revolutionized the management of certain hematologic malignancies (such as B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and multiple myeloma) that have failed conventional treatments, significantly improving the survival of patients who were previously considered incurable. In this review, we focus on bispecific T-cell engagers (BiTEs), which we will refer to as “bispecific antibodies” for clarity. These molecules have two specific targets: one that engages the immune system (typically T lymphocytes via CD3) and another that targets a tumor antigen. They exert a direct antitumor effect by physically bringing the immune system into close proximity with the tumor and activating T cells (leading to proliferation, differentiation, release of cytotoxic granules, and production of pro-inflammatory cytokines) upon contact with the tumor. Clinical trials and indications for bispecific antibodies are rapidly expanding. Their role is well established in hematology (B-cell acute lymphoblastic leukemia, multiple myeloma, follicular lymphoma, diffuse large B-cell lymphoma), while it is just beginning in solid tumor oncology, and progressively extending to certain systemic diseases. These therapies can cause complications similar to those seen with CAR-T cells, including cytokine release syndrome, specific neurological toxicity, sepsis and septic shock, and cytopenias. While these complications occur roughly half as often as in patients treated with CAR-T cells, they can still be life-threatening and may require admission to intensive care. Patients admitted to the intensive care units following bispecific antibody therapy have been still poorly described in the literature. This review article aims at reviewing the mechanism of action, the indications, and the complications of bispecific antibodies, for intensivists.