Bispecific Antibody Toxicity

Excerpt

Bispecific antibodies (bsAbs) have gained significant attention in recent years as a promising class of therapeutic agents designed to target multiple antigens simultaneously (see Image. Blinatumomab Mechanism of Action). These unique antibodies are engineered to recognize and bind to 2 distinct epitopes, allowing for a broader range of applications in treating various diseases, including cancer, autoimmune disorders, and infectious diseases. The FDA has already approved the following bsAbs for marketing in the US:

1. Blinatumomab (2014): For CD19-positive B-cell precursor acute lymphoblastic leukemia therapy

2. Emicizumab (2017): For reducing bleeding frequency in Hemophilia A with factor VIII inhibitors

3. Amivantamab (2021): For treating locally advanced or metastatic non–small cell lung cancer with epidermal growth factor receptor exon-20 insertion mutation

4. Faricimab (2022): For therapy of neovascular age-related macular degeneration and diabetic macular edema

5. Teclistamab (2022): For relapsed or refractory multiple myeloma treatment

6. Mosunetuzumab (2022): For relapsed or refractory follicular lymphoma therapy

7. Epcoritamab and glofitamab (2023): For treating relapsed or refractory diffuse large B-cell lymphoma

8. Talquetamab and elranatamab (2023): For therapy of relapsed or refractory multiple myeloma

While bsAbs offer exciting therapeutic possibilities, their use raises concerns about potential toxicity. These agents' adverse effects include cytopenias, diarrhea, transaminitis, and tumor lysis syndrome (TLS), which are also seen with conventional chemotherapy. Side effects unique to bsAbs include cytokine release syndrome (CRS), neurotoxicity (including immune effector cell-associated neurotoxicity syndrome or ICANS), and tumor flare.