Bispecific antibodies engaging T-cells have emerged as an innovative form of immunotherapy, seamlessly combining two antigen-recognizing elements into a single structure. This unique design enables the antibody to engage with two distinct targets simultaneously and to bring them into close proximity. By binding to both a T-cell and a cancer cell concurrently, it triggers a potent antitumor immune response, ultimately leading to the destruction of cancer cells. Notably, the specificity of bispecific antibodies reduces collateral damage to healthy cells in the vicinity, introducing a more targeted and potentially more effective treatment approach for patients.

Bispecific antibodies have shown great promise in cancer treatment. However, they have the potential for unique toxicities and safe administration requires collaboration between a multidisciplinary team to closely monitor patients and proactively manage potential side effects such as cytokine release syndrome (CRS) and neurotoxicity, specifically, immune effector cell-associated neurotoxicity (ICANs).

Severe toxic side effects

Bispecific antibodies can cause over activation and dysregulation of the immune system, with a large number of activated white blood cells releasing inflammatory cytokines. Cytokine release syndrome (CRS) and neurotoxicity (specifically immune effector cell-associated neurotoxicity syndrome, or ICANs) can be life threatening and require urgent management; therefore, patients receiving bispecific antibodies may need to be closely monitored in hospital during the initial doses, when the risk of CRS and ICANS are highest.

CRS is an acute systemic inflammatory reaction characterized by fever, hypotension, hypoxia and multi-organ dysfunction.

ICANs is a neurological syndrome that ranges from mild confusion to speech disturbances, seizures, motor weakness, and rarely cerebral edema or coma. CRS and ICANS may occur together or independently.

Immunosuppression, particularly among patients with lymphoma/myeloma, is common and may be profound. Hypogammaglobulinemia is common and the risk of infection may be increased, despite normal blood counts.

Other common side effects

• Abnormal blood tests/Low blood count
• Fever
• Infections
• Rash
• Joint pain
• Muscle pain
  
• Nausea
• Shortness of breath
• Swelling

For more details and management recommendations, see the BC Cancer Supportive Care CRS and ICANS management guidelines (links below).