From the Guidelines
Bispecific antibody therapy for cancer commonly causes cytokine release syndrome (CRS), neurotoxicity, and hematologic toxicities, with infection rates ranging between 33% and 76%, indicating an increased infection risk through BCMA signaling effects 1.
Common Toxicities
The toxicities associated with bispecific antibody therapy include:
- Cytokine release syndrome (CRS)
- Neurotoxicity
- Hematologic toxicities, such as neutropenia, thrombocytopenia, and anemia
- Infusion reactions with symptoms like fever, chills, and hypotension
- Treatment-related infections due to immunosuppression
- Tumor lysis syndrome in patients with high tumor burden
Management of Toxicities
Management of these toxicities typically involves:
- Tocilizumab and corticosteroids for CRS
- Neurological monitoring
- Antimicrobial prophylaxis
- Supportive care The severity of toxicities often correlates with disease burden and tends to decrease after initial doses as tumor burden diminishes 1.
Infection Risk
Patients with multiple myeloma (MM) are at increased risk of infections due to immune impairment and dysfunction of the adaptive immune response, with bispecific antibody therapy further increasing this risk 1.
Guidance on Infection Management
Guidance on the diagnosis of infections, monitoring, prophylaxis, and treatment is needed for patients receiving bispecific antibody therapy, with general guidelines and recommendations available for the management and prophylaxis of infections in patients with MM 1.
From the Research
Common Toxicities of Bispecific Antibody Therapy for Cancer
- Cytokine release syndrome (CRS) is a common acute toxicity in T-cell therapies, including T-cell-engaging bispecific antibodies (T-BiSp) 2, 3, 4, 5
- Neurotoxicity presents as neurological symptoms 2
- On-target, off-tumour toxicity damages healthy cells 2
- The incidence and severity of these toxicities vary based on the type of bispecific antibody, dose, patient factors, and tumor characteristics 2
Management of Toxicities
- Early recognition, dose modification, supportive care, and, in severe cases, immunosuppressive therapy or treatment discontinuation are crucial for managing toxicities 2, 4
- Tocilizumab, an IL-6 receptor antibody, can prevent CRS without affecting antitumor activity of bispecific antibodies 4
- Dexamethasone, a steroid, can inhibit T cell proliferation and antitumor activity, and is not recommended for CRS prevention in bispecific antibody therapy 4
Pathophysiology and Clinical Presentation of Cytokine Release Syndrome
- CRS is triggered by on-target effects induced by binding of chimeric antigen receptor (CAR) T cells or bispecific antibody to its antigen and by subsequent activation of bystander immune and non-immune cells 5
- CRS is associated with high circulating concentrations of several pro-inflammatory cytokines, including interleukins, interferons, tumor necrosis factors, colony-stimulating factors, and transforming growth factors 5