From the Guidelines
Monoclonal antibody treatments can cause a wide range of immune-related adverse effects, including skin, gut, endocrine, lung, and musculoskeletal irAEs, as well as less common but serious cardiovascular, hematologic, renal, neurologic, and ophthalmologic irAEs, with an overall incidence of ≤30% in phase 3 trials of anti-PD-1/PD-L1 agents 1.
Common Immune-Related Adverse Effects
Some of the common immune-related adverse effects associated with monoclonal antibody treatments include:
- Skin irAEs, such as rash and dermatitis
- Gut irAEs, such as colitis and diarrhea
- Endocrine irAEs, such as thyroiditis and hypophysitis
- Lung irAEs, such as pneumonitis
- Musculoskeletal irAEs, such as arthritis and myositis
Less Common but Serious Immune-Related Adverse Effects
Less common but serious immune-related adverse effects include:
- Cardiovascular irAEs, such as myocarditis and pericarditis
- Hematologic irAEs, such as anemia and neutropenia
- Renal irAEs, such as nephritis and renal failure
- Neurologic irAEs, such as encephalitis and meningitis
- Ophthalmologic irAEs, such as uveitis and optic neuritis
Incidence and Severity of Immune-Related Adverse Effects
The incidence of immune-related adverse effects varies depending on the specific monoclonal antibody and the patient population, with an overall incidence of ≤30% in phase 3 trials of anti-PD-1/PD-L1 agents 1. The severity of immune-related adverse effects can range from mild to life-threatening, with some patients experiencing serious and occasionally life-threatening irAEs, such as severe colitis, pneumonitis, and encephalitis 1.
Delayed Onset and Prolonged Duration of Immune-Related Adverse Effects
Immune-related adverse effects can have a delayed onset and prolonged duration compared to adverse events resulting from chemotherapy, with some patients presenting with irAEs late in the course of treatment, and in some cases, months or even years after treatment discontinuation 1.
From the FDA Drug Label
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously Immune-mediated pneumonitis occurred in 3.1% (61/1994) of patients receiving OPDIVO as a single agent, including Grade 4 (<0.1%), Grade 3 (0.9%), and Grade 2 (2.1%) adverse reactions. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) adverse reactions.
Immune-related adverse effects of monoclonal antibodies may include:
- Immune-mediated pneumonitis: a potentially fatal condition that can occur at any time after starting treatment
- Severe and fatal immune-mediated adverse reactions: can occur in any organ system or tissue and can affect more than one body system simultaneously
- Other immune-mediated adverse reactions, such as endocrinopathies and dermatologic reactions, can also occur
These adverse effects can be severe and potentially fatal, and early identification and management are essential to ensure safe use of monoclonal antibodies 2, 3, 3.
From the Research
Immune-Related Adverse Effects of Monoclonal Antibodies
The administration of monoclonal antibodies (mAbs) can lead to various immune-related adverse effects, including:
- Acute anaphylaxis 4
- Serum sickness 4
- Generation of antibodies 4
- Infections 4, 5
- Cancer 4
- Autoimmune disease 4
- Organ-specific adverse events, such as cardiotoxicity 4
- Infusion reactions, which are the most frequent adverse effects 6
- Cytokine release syndrome, a life-threatening condition that can occur during the first-in-human study with certain mAbs, such as TGN1412 4
Mechanism of Action and Adverse Effects
The mechanism of action of mAbs is highly specific binding to their target antigen and interaction with the immune system, which can lead to adverse effects 6. The use of mAbs, such as nivolumab, can promote anti-tumor immunity but may also lead to immune-related adverse effects, including those related to the combination therapy with other agents 7, 8.
Infectious Complications
Infectious complications are a significant concern with the use of mAbs, and the risks of infection and infectious disease-related complications vary depending on the specific agent and the underlying disease process 5. Post-marketing surveillance is essential for identifying adverse reactions and improving knowledge of the mechanism of action of mAbs 6.