What are the considerations and treatment options for immunotherapy?

From the Guidelines

Immunotherapy treatment should be carefully considered based on patient factors, cancer type, and potential side effects, with checkpoint inhibitors like pembrolizumab, nivolumab, and ipilimumab being key options, as recommended by the most recent guidelines 1. When considering immunotherapy, it is essential to evaluate the patient's overall health, cancer type, and stage, as well as biomarkers such as PD-L1 expression and tumor mutational burden. The treatment selection process should be individualized, taking into account the specific characteristics of the patient and their cancer.

• Checkpoint inhibitors, including pembrolizumab, nivolumab, and ipilimumab, are administered intravenously every 2-6 weeks, depending on the specific drug and indication.
• CAR T-cell therapy involves modifying a patient's own T-cells to target cancer cells and is primarily used for certain blood cancers.
• Monoclonal antibodies, such as rituximab, target specific cancer cell proteins and are often administered weekly for 4 weeks.
• Cancer vaccines, like Sipuleucel-T for prostate cancer, and cytokines, including interleukin-2 and interferon, represent additional approaches. The management of immune-related adverse events is crucial, with prompt treatment using corticosteroids, such as prednisone 1-2 mg/kg/day, and potentially other immunosuppressants, as outlined in the guidelines 1. Regular monitoring through physical exams, laboratory tests, and imaging is essential throughout treatment, with effectiveness typically assessed every 2-3 months.
• The use of biomarkers, such as PD-L1 expression and tumor mutational burden, can help predict response to immunotherapy, although their clinical validation and regulatory considerations are complex 1.
• The Society for Immunotherapy of Cancer has provided consensus recommendations for the treatment of advanced renal cell carcinoma, including the use of nivolumab, ipilimumab, and pembrolizumab 1. In summary, immunotherapy treatment options should be carefully selected based on individual patient factors, cancer type, and potential side effects, with a focus on maximizing clinical benefits while minimizing toxicity, as supported by the most recent and highest-quality evidence 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)].