From the Guidelines
Immunotherapy treatment should be considered as a first-line systemic treatment option for patients with newly diagnosed pleural mesothelioma, with ipilimumab plus nivolumab being a recommended combination. When considering immunotherapy, patient factors, cancer type, and potential side effects should be carefully evaluated. Before starting immunotherapy, patients should undergo comprehensive evaluation including biomarker testing (like PD-L1 expression or MSI status), assessment of autoimmune conditions, and organ function tests 1. Common immunotherapy medications include checkpoint inhibitors (pembrolizumab, nivolumab, atezolizumab, durvalumab) typically given intravenously every 2-6 weeks, CAR T-cell therapies (like Kymriah or Yescarta) for certain blood cancers, and cytokines (interleukin-2, interferon) for specific cancers.
Key Considerations
- Treatment duration varies from fixed periods (often 1-2 years) to indefinite treatment until disease progression or unacceptable toxicity.
- Side effects can include immune-related adverse events affecting various organs, requiring prompt management with corticosteroids (often starting with prednisone 1-2 mg/kg/day) and sometimes immunosuppressants like infliximab for severe cases.
- Regular monitoring during treatment includes symptom assessment, blood tests, and imaging studies.
- Immunotherapy works by enhancing the body's natural immune response against cancer cells, either by removing inhibitory signals that prevent T-cells from attacking cancer (checkpoint inhibitors) or by directly boosting immune cell activity (cytokines, CAR T-cells) 1.
Recent Guidelines
The most recent guidelines from 2025 recommend ipilimumab plus nivolumab as a first-line systemic treatment option for patients with newly diagnosed pleural mesothelioma, with a strong strength of recommendation 1. Additionally, the guidelines suggest that PD-L1, TMB, or MSI should not be used to determine the choice of chemotherapy or immunotherapy in patients with pleural mesothelioma.
Biomarker Testing
Biomarker testing, such as PD-L1 expression or MSI status, is an essential part of the comprehensive evaluation before starting immunotherapy. However, the validation of biomarkers to predict response to immunotherapy is a complex process that requires careful consideration of pre-analytical and analytical aspects, as well as clinical validation and regulatory considerations 1.
From the FDA Drug Label
The safety of OPDIVO in combination with chemotherapy or in combination with ipilimumab was evaluated in CHECKMATE-648, a randomized, active-controlled, multicenter, open-label trial in patients with previously untreated unresectable advanced, recurrent or metastatic ESCC [see Clinical Studies (14. 13)]. Serious adverse reactions occurred in 62% of patients receiving OPDIVO in combination with chemotherapy and in 69% of patients receiving OPDIVO in combination with ipilimumab.
The considerations and treatment options for immunotherapy with nivolumab (OPDIVO) include:
- Serious adverse reactions: occurring in 62% of patients receiving OPDIVO in combination with chemotherapy and in 69% of patients receiving OPDIVO in combination with ipilimumab 2
- Adverse reactions leading to discontinuation: of OPDIVO in 7% of patients and dose interruption in 26% of patients 2
- Grade 3 and 4 adverse reactions: occurring in 41% of patients receiving OPDIVO, including increased gamma-glutamyl transferase and diarrhea 2
- Common adverse reactions: including fatigue, musculoskeletal pain, rash, and pruritus 2
- Laboratory abnormalities: such as increased ALT, AST, and alkaline phosphatase 2 2 Key considerations for immunotherapy with nivolumab include:
- Monitoring for adverse reactions: and laboratory abnormalities
- Dose interruption or discontinuation: in case of serious adverse reactions
- Combination with other therapies: such as chemotherapy or ipilimumab, which may increase the risk of adverse reactions.
From the Research
Considerations for Immunotherapy
- Immunotherapy is a relatively new treatment modality that has shown promising results in the treatment of various types of cancer, including advanced non-small cell lung cancer [(3,4)].
- The immune system plays a critical role in the recognition and eradication of tumor cells, and immunotherapies based on this concept have been used for decades with some success against a few tumor types 3.
- However, most immunotherapies were limited by a lack of either substantial efficacy or specificity, resulting in toxicity 3.
- Recent studies have identified key molecules that govern the interactions between the immune system and tumors, revitalizing the interest in immunotherapy as an evolving treatment modality [(3,5)].
Treatment Options for Immunotherapy
- Immunotherapies have potentially complementary mechanisms of action that may allow them to be combined with other immunotherapeutics, chemotherapy, targeted therapy, or other traditional therapies [(3,6)].
- Examples of immunotherapeutics include ipilimumab, an antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor immune responses 3.
- The programmed death-1 (PD-1) checkpoint inhibitors are promising immunotherapies with demonstrated sustained antitumor responses in several tumors [(3,5)].
- Combination therapies, such as immunotherapy with chemotherapy, radiation therapy, and targeted therapy, have shown promising results in clinical trials 6.
Efficacy and Safety of Immunotherapy
- Clinical trial results have shown that immunotherapy can be an effective treatment option for patients with advanced cancer, with some studies demonstrating improved overall survival rates and progression-free survival rates [(4,7)].
- However, treatment-related adverse events can occur, and the efficacy and safety of immunotherapy can vary depending on the specific treatment and patient population 4.
- Further research is needed to identify the most effective combination therapies and to optimize the use of immunotherapy in the treatment of cancer [(6,5)].