From the Guidelines
No, immune checkpoint inhibitors (ICIs) do not cause immunosuppression, but rather enhance the immune system's ability to fight cancer. According to the study by Slimano et al. 1, ICIs, such as anti-PD-1 and anti-PD-L1 monotherapy, do not induce immunosuppression. In fact, preliminary analyses did not show a detrimental effect of immunotherapy compared to other anticancer treatments in patients with COVID-19 1.
The mechanism of action of ICIs involves blocking proteins that normally keep immune responses in check, allowing T cells to become more active in recognizing and attacking cancer cells. This enhanced immune response can lead to side effects known as immune-related adverse events (irAEs), which are essentially overactive immune responses affecting various organs.
However, it's essential to note that while ICIs boost immune function against cancer, patients may still be at increased risk for certain infections due to the overall changes in immune regulation. To mitigate this risk, healthcare providers should monitor patients on these medications closely for both signs of treatment efficacy and potential immune-related side effects.
Some key considerations for the use of ICIs in patients with cancer include:
- Curative or palliative objective
- Patient age and life expectancy
- Number of treatment lines
- Risk of lymphopenia and cumulative risk with COVID-19 symptoms
- Potential for cytokine release syndrome between ICIs or CAR-T cells and cytokine storm in severe COVID-19 infection
In terms of specific treatment adjustments, the study suggests that a reduced frequency of administration and increased dose of ICIs, such as nivolumab and pembrolizumab, may be considered to minimize the risk of immunosuppression and COVID-19-related complications 1.
Overall, the use of ICIs in patients with cancer requires careful consideration of the potential benefits and risks, as well as close monitoring for immune-related adverse events.
From the FDA Drug Label
The trial excluded patients with autoimmune disease and patients requiring chronic systemic treatment with corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications.
The FDA drug label does not answer the question.
From the Research
Immune Checkpoint Inhibitors and Immunosuppression
- Immune checkpoint inhibitors (ICIs) are designed to restore T-cell effector function by targeting immune checkpoint molecules that activate immunosuppressive pathways 2.
- The use of ICIs does not seem to generally increase the risk of infection, but they might increase susceptibility to certain infections, such as tuberculosis 2.
- ICIs can reinvigorate immune responses, which may play a significant role in pathogen clearance and have a positive impact on chronic infectious diseases, such as HIV infection 2.
- Immunosuppressants used to treat immune-related adverse events (irAEs) caused by ICIs can have unfavorable effects on ICI efficacy and survival 3.
- The treatment of irAEs with immunosuppressants requires a balance between preventing fatality or chronicity and maintaining ICI efficacy 3.
Mechanism of Action
- ICIs work by blocking the immune checkpoint molecules that suppress the immune response, allowing the immune system to attack cancer cells more effectively 4, 5.
- The activation of immune checkpoint pathways by cancer cells can lead to immune suppression, which is a major obstacle to effective cancer treatment 5.
Clinical Evidence
- ICIs have demonstrated a dramatic improvement in overall survival in patients with advanced melanoma and squamous non-small cell lung cancer (NSCLC) 4.
- The therapeutic outcomes of ICIs vary depending on the type of cancer, patient population, and biomarkers 5, 6.
- Biomarkers, such as PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures, are being developed to predict the response to ICIs and immune-related adverse events 5, 6.