A new type of immunotherapy is gaining traction in the treatment of solid tumors and hematologic malignancies. Bi-specific T-cell engager (BiTE) treatments are now approved for the treatment of Acute Lymphoid Leukemia, Follicular and diffuse large cell lymphomas, Multiple Myeloma, and Metastatic Uveal Melanoma.
BiTE therapies are off-the-shelf monoclonal antibodies that deploy two binding domains. One of the sites attaches to the tumor-specific antigen on the cancer cell and the other to the patient’s cancer-killing T-cell. BiTEs essentially recruit T-cells directly to the tumor cell for cell lysis. The cytotoxic potential of the T cell is activated, ridding the body of the malignant cell.
This type of precision medicine has been shown to provide deep and durable responses in heavily pre-treated patients. Impressive response rates and improvements in overall survival have been shown.
BiTE therapies are initially administered in the hospital, with most treatments requiring a 5–7-day admission. They are administered via intravenous or subcutaneous routes utilizing a step-up dosing regimen. After the initial step-up dosing, most patients will receive the remainder of their therapy as outpatients.
BiTE therapy is associated with potential serious side effects including Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). CRS can occur if the patient’s immune system gets highly upregulated in response to the BiTE treatments. Symptoms may include fevers, chills, headache, tachycardia, shortness of breath, rash, nausea, and hypotension. In severe cases, this can lead to life-threatening multiorgan failure.
ICANS presents with cognitive changes including confusion, word-finding difficulty, hallucinations, headaches, tremors, and impaired fine motor skills. In critical cases, seizures and cerebral edema can occur. Close monitoring by all healthcare staff including frequent neurologic assessments and vital signs can minimize these severe reactions. This is the rationale for in-patient administration during step-up dosing. Treatment for both CRS and ICANS is available and must be given promptly to minimize the potentially toxic effects of BiTE treatment.
Other side effects of BiTE therapies may include fatigue, rash, pyrexia, injection site reactions, infections, cytopenias, and tumor flare. Because of the potential for severe reactions and the need for immediate treatment, BiTE treatments are only available to providers and institutions that have completed Risk Evaluation and Mitigation Strategy (REMS) training. This ensures patient safety remains a top priority.
The landscape of immune-oncology treatments is rapidly changing. The success of BiTE therapies is expanding the platform. BiTE therapy is being investigated in numerous tumor types which will hopefully lead to more therapeutic options in the future for all patients with a cancer diagnosis.
References
Einsele, H., Borghaei, H., Orlowski, R.Z., Subklewe, M., Roboz, G.J., Zugmaier, G., Kufer, P., Iskander, K. and Kantarjian, H.M. (2020), The BiTE (bispecific T-cell engager) platform: Development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer, 126: 3192-3201. https://doi.org/10.1002/cncr.32909
Klein, C., Brinkmann, U., Reichert, J.M. et al. The present and future of bispecific antibodies for cancer therapy. Nat Rev Drug Discov (2024). https://doi.org/10.1038/s41573-024-00896-6
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