Safety and efficacy of bispecific antibodies in hematologic neoplasms: a systematic review.

Hematologic neoplasms remain a growing global burden, with relapse, resistance, and limited treatment options persisting. Bispecific antibodies (BsAbs) offer a novel multi-antigen targeting strategy. This systematic review assesses their efficacy and safety, offering an in-depth appraisal of their therapeutic potential and the unmet medical needs. We conducted this systematic review following the PRISMA 2020 guidelines. Articles published up to 20 June 2026 were searched across PubMed, Scopus, Web of Science, and Embase. Efficacy outcomes such as measurable residual disease (MRD), overall response rate (ORR), complete response (CR), overall survival (OS), and progression-free survival (PFS), as well as safety outcomes such as severe adverse events (SAEs), grade ≥3 adverse events (≥3 AEs), hematologic and non-hematologic toxicities were systematically evaluated. Thirty-six studies evaluating nineteen different BsAbs were included. Blinatumomab (CD3-CD19) remains the most extensively studied bispecific antibody in relapsed or refractory B-cell precursor acute lymphoblastic leukemia (R/R BCP-ALL). CD3-CD20 BsAbs (Glofitamab, Epcoritamab) demonstrated durability in non-Hodgkin lymphoma (NHL). In multiple myeloma (MM), BCMA- and GPRC5D-targeting BsAbs achieved MRD negativity and deep responses including very good partial response (VGPR) and stringent complete response (sCR). BsAbs in acute myeloid leukemia (AML) and Hodgkin/T-cell lymphoma (HL/TCL) remained early-phase with limited efficacy and no approvals to date. Cytokine release syndrome (CRS) and neurotoxicity were the dominant toxicities of CD3-engaging agents (neurologic events >50% in several Blinatumomab studies). Teclistamab (CD3-BCMA) and Talquetamab (CD3-GPRC5D) were associated with frequent CRS, with neurotoxicity also reported. However, hematologic toxicity and infections remain major challenges in multiple myeloma treatment. BsAbs demonstrate established clinical activity in BCP-ALL, B-cell NHL, and MM but remain under investigation in AML, HL, and T-cell lymphoma. CRS, neurotoxicity, cytopenias, and infections remain key safety considerations. Further studies should optimize treatment strategies and evaluate emerging targets and non-CD3-engaging bispecific antibodies.The protocol was prospectively registered in PROSPERO (CRD42023467556). https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023467556.