What Is Immunotherapy for Mesothelioma?

How Immunotherapy Works

Immunotherapy is a fundamentally different approach from traditional cancer treatments like chemotherapy and radiation. Rather than directly attacking cancer cells, immunotherapy works by enhancing or restoring the body's own immune system so it can better recognize and destroy cancer.

Under normal circumstances, the immune system identifies and eliminates abnormal cells. However, cancer cells can evade immune detection by exploiting natural "checkpoints" — molecular switches on immune cells that normally prevent the immune system from attacking healthy tissue. Mesothelioma cells hijack these checkpoints to effectively hide from immune surveillance.

Checkpoint inhibitors, the class of immunotherapy drugs approved for mesothelioma, work by blocking these checkpoints and removing the "brakes" on the immune response. This allows T-cells (a type of white blood cell) to recognize mesothelioma cells as threats and mount an attack against them. The National Cancer Institute provides detailed information on how various types of immunotherapy function.

FDA-Approved: Opdivo Plus Yervoy

On October 2, 2020, the U.S. Food and Drug Administration approved the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) as the first immunotherapy treatment for malignant pleural mesothelioma. This approval marked a significant milestone — it was the first new systemic treatment approved for mesothelioma in 16 years, since pemetrexed was approved in 2004.

The approved indication is for adult patients with unresectable (not removable by surgery) malignant pleural mesothelioma who have not received prior treatment. This means it is approved as a first-line treatment — the initial therapy a patient receives after diagnosis, rather than a backup option after other treatments fail.

Nivolumab (Opdivo) is a PD-1 inhibitor. It blocks the PD-1 protein on T-cells, which cancer cells exploit to avoid immune attack. By blocking PD-1, nivolumab allows T-cells to recognize and kill mesothelioma cells.

Ipilimumab (Yervoy) is a CTLA-4 inhibitor. It blocks a different checkpoint protein, CTLA-4, which normally dampens the immune response. By blocking CTLA-4, ipilimumab amplifies the overall immune response against the cancer.

The two drugs work on complementary pathways, and their combination produces a stronger anti-tumor immune response than either drug alone.

CheckMate 743 Trial Results

The FDA approval was based on the results of CheckMate 743, a Phase III randomized clinical trial that enrolled 605 patients with previously untreated, unresectable malignant pleural mesothelioma across 103 sites in 21 countries.

The trial compared Opdivo plus Yervoy against the standard chemotherapy regimen of pemetrexed plus cisplatin or carboplatin. The key findings were significant.

Overall survival. Patients receiving Opdivo plus Yervoy achieved a median overall survival of 18.1 months, compared to 14.1 months for patients receiving chemotherapy. This represents a 26% reduction in the risk of death.

Non-epithelioid benefit. The survival advantage was particularly striking in patients with non-epithelioid (sarcomatoid and biphasic) cell types. These patients had a median overall survival of 18.1 months with immunotherapy versus just 8.8 months with chemotherapy — more than double the survival time. This is especially significant because non-epithelioid mesothelioma has historically been the most difficult to treat.

Duration of response. Among patients who responded to immunotherapy, the responses tended to be more durable (longer-lasting) than responses to chemotherapy, suggesting that the immune system can provide ongoing cancer control once activated.

The two-year survival rate was 41% for the immunotherapy group compared to 27% for the chemotherapy group, reinforcing the long-term benefit of this approach.

Other Immunotherapy Drugs in Development

While Opdivo plus Yervoy is currently the only FDA-approved immunotherapy for mesothelioma, several other immunotherapy drugs and combinations are being studied in clinical trials.

Pembrolizumab (Keytruda). This PD-1 inhibitor, widely used in other cancers, is being studied in multiple mesothelioma trials — both as a single agent and in combination with chemotherapy or other immunotherapy drugs. Early results have shown activity in mesothelioma, particularly in patients whose tumors express PD-L1.

Immunotherapy plus chemotherapy. Researchers are investigating whether combining checkpoint inhibitors with standard chemotherapy can improve outcomes beyond either approach alone. Several trials are exploring this strategy for both first-line and second-line treatment.

Novel immunotherapy approaches. Beyond checkpoint inhibitors, researchers are studying CAR T-cell therapy (engineered immune cells), cancer vaccines, and oncolytic virus therapy for mesothelioma. While most of these are in early-phase trials, they represent potential future treatment options.

Side Effects and Who Qualifies

Immunotherapy side effects differ from chemotherapy side effects because they result from an overactive immune response rather than the direct toxicity of the drugs. Common side effects of Opdivo plus Yervoy include fatigue, decreased appetite, nausea, rash, diarrhea, and musculoskeletal pain.

More serious immune-related side effects can occur when the activated immune system attacks healthy organs. These may include inflammation of the lungs (pneumonitis), liver (hepatitis), colon (colitis), thyroid (thyroiditis), or other organs. These side effects require prompt medical attention and may be managed with corticosteroids or temporary treatment interruption. Your oncologist will monitor for these reactions through regular check-ups and blood tests.

Who qualifies for Opdivo plus Yervoy: The FDA approval covers adults with unresectable malignant pleural mesothelioma who have not received prior systemic therapy. Patients must have adequate organ function and a performance status that allows them to tolerate treatment. Your oncologist will evaluate whether immunotherapy is appropriate based on your specific diagnosis, cell type, and overall health.

Patients with peritoneal mesothelioma or those who have already received prior treatment may access immunotherapy through clinical trials or off-label use, depending on their oncologist's recommendation.

Future Directions

Immunotherapy research for mesothelioma is advancing rapidly. Ongoing and planned studies are exploring combinations of immunotherapy with surgery and radiation, biomarkers that predict which patients will respond best to immunotherapy, strategies to overcome immunotherapy resistance, and new classes of immunotherapy agents.

As research continues, immunotherapy is expected to play an increasingly important role in mesothelioma treatment, potentially in combination with existing treatment approaches to further improve outcomes for patients at all stages of the disease.