Essential Questions to ask if you or a loved one has been diagnosed with Mesothelioma ***IMPORTANT***

Immune Checkpoint Inhibitors

Posted on: April 1, 2024 *Updated on: May 27, 2024

Immune checkpoint inhibitors have revolutionized the treatment of various cancers, including inoperable pleural mesothelioma, by enhancing the body’s immune response against cancer cells. These drugs are part of a broader category of therapies known as immunotherapy, which leverages the body’s immune system to fight cancer. Checkpoint inhibitors specifically target and block immune checkpoints, which are molecular brakes that cancer cells exploit to evade detection and destruction by the immune system

Mechanism of Action

  • PD-1/PD-L1 Checkpoint: Programmed death-1 (PD-1) is a receptor on T-cells, a type of white blood cell pivotal for the immune response. PD-L1, its ligand, is often overexpressed on the surface of cancer cells. When PD-1 binds to PD-L1, the immune response is dampened, allowing cancer cells to evade immune surveillance. Checkpoint inhibitors targeting this pathway, such as nivolumab (Opdivo) and pembrolizumab (Keytruda), block this interaction, thereby enhancing the immune system’s ability to recognize and destroy cancer cells.
  • CTLA-4 Checkpoint: Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is another receptor that downregulates the immune response, but it operates earlier in the immune response cycle than PD-1. By inhibiting CTLA-4, drugs like ipilimumab (Yervoy) amplify T-cell activation and proliferation, bolstering the immune system’s cancer-fighting capabilities.

FDA-Approved Checkpoint Inhibitors for Mesothelioma

  • Opdivo (nivolumab) + Yervoy (ipilimumab): This combination has received FDA approval for the treatment of inoperable pleural mesothelioma, offering a new line of therapy for patients with this challenging condition. The combination therapy targets both the PD-1/PD-L1 and CTLA-4 checkpoints, providing a dual approach to enhancing the immune response against mesothelioma cells.
  • Imfinzi® (durvalumab): Targets the PD-1/PD-L1 pathway, approved for certain types of cancer and studied in mesothelioma.
  • Imjudo® (tremelimumab): Another CTLA-4 targeting drug, sometimes used in combination with drugs targeting the PD-1/PD-L1 pathway for a more comprehensive immune response.

Clinical Benefits and Considerations

Checkpoint inhibitors have shown significant promise in improving survival rates and quality of life for patients with various cancers, including mesothelioma. However, these treatments are not without potential side effects, given their mechanism of boosting the immune system, which can sometimes attack healthy tissues as well. Common side effects include fatigue, skin rash, and colitis, with more severe immune-mediated effects occurring less frequently.

Conclusion

The development and approval of immune checkpoint inhibitors mark a significant advancement in cancer therapy, offering hope to patients with previously intractable forms of cancer. Their use in mesothelioma underscores the potential of immunotherapy to change the landscape of cancer treatment, providing patients with more effective and targeted options. Continued research and clinical trials are essential to further understand the full potential and limitations of these innovative therapies.