Mesothelioma is a rare and aggressive cancer that originates in the lining of the lungs, abdomen, or heart, most commonly linked to asbestos exposure. Immunotherapy has emerged as a significant and evolving approach in managing this disease. This treatment harnesses the body’s natural defenses to combat cancer cells.
Understanding Immunotherapy
Immunotherapy represents a distinct approach to cancer treatment, differing from traditional methods like chemotherapy or radiation. While chemotherapy uses drugs to directly kill fast-growing cells, and radiation therapy uses high-energy rays to destroy cancer cells in a targeted area, immunotherapy works differently. It functions by stimulating or augmenting a patient’s own immune system to recognize and attack malignant cells.
The immune system naturally possesses mechanisms to identify and eliminate abnormal cells, but cancer cells often develop ways to evade this detection. Immunotherapy aims to overcome these evasion strategies. It empowers the body’s existing defenses to mount a more robust and sustained response against the tumor.
Immunotherapy’s Role in Mesothelioma Treatment
Immunotherapy has become a promising treatment strategy for mesothelioma, particularly for patients with unresectable malignant pleural mesothelioma. The primary types of immunotherapy used for mesothelioma are immune checkpoint inhibitors, which block certain proteins on immune cells or cancer cells that act as “brakes” on the immune response. By releasing these brakes, the immune system can more effectively recognize and eliminate cancer.
One significant class of these inhibitors targets the PD-1/PD-L1 pathway. Programmed death-1 (PD-1) is a protein on T-cells, a type of immune cell, and programmed death-ligand 1 (PD-L1) is often found on cancer cells, including mesothelioma cells. When PD-1 binds to PD-L1, it signals the T-cell to stand down, preventing it from attacking the cancer. Drugs like nivolumab and pembrolizumab are PD-1 inhibitors that block this interaction, allowing T-cells to remain active and fight the tumor.
Another important target is CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), an immune checkpoint protein found on T-cells that also acts as an inhibitory signal. Ipilimumab is a CTLA-4 inhibitor that blocks this protein, enhancing T-cell activation and proliferation. Combining a PD-1 inhibitor like nivolumab with a CTLA-4 inhibitor like ipilimumab has shown improved outcomes for some patients with unresectable malignant pleural mesothelioma. This combination therapy simultaneously releasing two different brakes on the immune system, leading to a more potent anti-tumor response.
Immunotherapy is often considered for mesothelioma patients who are not candidates for surgery or whose disease has progressed after chemotherapy. For instance, the combination of nivolumab and ipilimumab is approved as a first-line treatment for unresectable malignant pleural mesothelioma. Pembrolizumab has also been explored as a treatment option, particularly in patients with PD-L1 positive tumors or those who have progressed on prior therapies. These therapies represent a significant advance, offering a different mechanism of action compared to traditional chemotherapy.
Patient Selection for Immunotherapy
Determining whether a patient with mesothelioma is a suitable candidate for immunotherapy involves a thorough evaluation by a multidisciplinary medical team. A patient’s overall health and performance status are important considerations, as immunotherapy requires a certain level of physical resilience. Patients generally need to have a good performance status, indicating they can carry out most daily activities.
The specific type of mesothelioma and its stage also influence treatment decisions. While immunotherapy is broadly applicable, certain histological subtypes, such as sarcomatoid or biphasic mesothelioma, may respond differently compared to epithelioid mesothelioma. Biomarkers, such as PD-L1 expression, are sometimes assessed, though their predictive value can vary. Prior treatments, including chemotherapy, also play a role.
Managing Treatment and Side Effects
Immunotherapy for mesothelioma is typically administered intravenously, meaning the medication is delivered directly into a vein. The frequency of infusions varies depending on the specific drug or combination, often ranging from every two to six weeks. The duration of treatment can extend for several months or even years, as long as the patient tolerates the therapy and the disease remains stable or responsive.
Patients receiving immunotherapy may experience immune-related adverse events (irAEs), which occur when the activated immune system targets healthy tissues. Common irAEs include fatigue, skin rashes, itching, and gastrointestinal issues like diarrhea or colitis. Less common but more severe irAEs can affect organs such as the lungs (pneumonitis), liver (hepatitis), or endocrine glands (thyroid dysfunction, adrenal insufficiency). Prompt reporting of any new or worsening symptoms to the medical team is important. Mild irAEs may be managed symptomatically, while more severe reactions often require temporary cessation of treatment and the administration of corticosteroids or other immunosuppressive medications.