Bispecific Antibodies in Hematologic Malignancies: Attacking the Frontline

Since blinatumomab's approval as the first bispecific antibody (BsAb) in cancer therapy, these immunomodulatory agents have achieved substantial success in lymphoid malignancies. A decade after provisional approval in relapsed settings, blinatumomab became part of first-line induction therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL). Now, six additional BsAbs have FDA approvals for the treatment of B-cell non-Hodgkin's lymphomas and multiple myeloma (MM), achieving high response rates in otherwise refractory scenarios. In lymphoma, epcoritamab, glofitamab, and mosunetuzumab show proof-of-principle for complete remission (CR) without chemotherapy or cell-based treatment. Single-agent remissions do not appear durable, but fortunately, these immunotherapies are readily combined with other treatment modalities. Therefore, their true potential to contribute to cures may be close on the horizon owing to ongoing and future trials. In MM, teclistamab, talquetamab, and elranatamab achieve impressive CR rates in the relapsed setting and similarly, are being investigated in earlier line combinations and in precursor entities such as smoldering myeloma and monoclonal gammopathy of undetermined significance (MGUS). With a unique mechanism of action and continued testing in earlier lines, BsAbs are poised to be among the winners in the race to the frontline treatment of hematologic malignancies.