How I prevent infections in adults receiving bispecific antibody therapies for advanced B-cell malignancies

ABSTRACT: T-cell-engaging bispecific antibodies (BsAbs) have transformed the treatment landscape for multiple hematologic malignancies and are under investigation in the frontline setting, within combination regimens, and for nonmalignant diseases. However, their increasing use has revealed new patterns of immune suppression and infectious complications that differ from other treatment modalities, including chimeric antigen receptor T-cell therapy. Notably, infections are frequent and represent the principal cause of nonrelapse mortality. These risks with repeated BsAb dosing arise from multifactorial mechanisms, including B-cell or plasma-cell aplasia, hypogammaglobulinemia, and early cytopenias. Additional contributors such as T-cell exhaustion, cytokine-directed immune modulation, and disease-related immunodeficiency, further compound infection risk. The result is a dynamic and cumulative impairment of host immunity that evolves over the course of therapy. In this "How I Treat" article, we provide a practical, phase-based framework for preventing and managing infections in patients receiving BsAbs for non-Hodgkin lymphoma or multiple myeloma. Our review includes pretreatment evaluation, the period of active therapy, and long-term follow-up. Using representative cases, we highlight strategies for infectious disease screening, antimicrobial prophylaxis, immunoglobulin supplementation, vaccination, and other supportive care practices. Our aim is to equip clinicians with an evidence-informed and pragmatic framework for mitigating BsAb-related infection risks.