Currently, the FDA has approved 16 different immunomodulators—nine checkpoint inhibitors, four cytokines, two adjuvants, and a small molecule with immunomodulatory properties—for the treatment of more than a dozen major cancer types. Most of these approvals cover cancers that are advanced or resistant to other forms of treatment, but more recently they’ve also been approved as the first systemic treatment a patient receives for several types of metastatic cancer.
Checkpoint Inhibitors
- Atezolizumab (Tecentriq®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with bladder cancer, breast cancer, liver cancer, lung cancer, and melanoma
- Avelumab (Bavencio®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with bladder cancer, kidney cancer, and Merkel cell carcinoma, a type of skin cancer
- Cemiplimab (Libtayo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with cutaneous squamous cell carcinoma, basal cell carcinoma, and lung cancer
- Dostarlimab (Jemperli): a checkpoint inhibitor that targets the PD-1 pathway; approved for subsets of patients with uterine (endometrial) cancer
- Durvalumab (Imfinzi™): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with bladder cancer and lung cancer
- Ipilimumab (Yervoy®): a checkpoint inhibitor that targets the CTLA-4 pathway; approved for subsets of patients with melanoma, mesothelioma, liver cancer, and lung cancer
- Nivolumab (Opdivo®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with bladder cancer, colorectal cancer, esophageal cancer, gastric cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, lymphoma, melanoma, and mesothelioma
- Pembrolizumab (Keytruda®): a checkpoint inhibitor that targets the PD-1/PD-L1 pathway; approved for subsets of patients with bladder cancer, breast cancer, cervical cancer, colorectal cancer, cutaneous squamous cell carcinoma, esophageal cancer, head and neck cancer, kidney cancer, liver cancer, lung cancer, lymphoma, melanoma, Merkel cell carcinoma, and stomach cancer. It is also approved to treat subsets of patients with cancers of any type that present with certain genetic mutations (MSI-H, dMMR, or TMB-H).
- Relatlimab: a checkpoint inhibitor that targets the LAG-3 pathway; approved in combination with nivolumab (together known as Opdualag™) for subsets of patients with melanoma
Cytokines
- Aldesleukin (Proleukin®): a cytokine that targets the IL-2/IL-2R pathway; approved for subsets of patients with kidney cancer and melanoma
- Granulocyte-macrophage colony-stimulating factor (GM-CSF): an immunomodulatory cytokine; approved for subsets of patients with neuroblastoma
- Interferon alfa-2a: a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with leukemia and sarcoma
- Interferon alfa-2b (Intron A®): a cytokine that targets the IFNAR1/2 pathway; approved for subsets of patients with leukemia, lymphoma, melanoma, and sarcoma
- Peginterferon alfa-2b (Sylatron®/PEG-Intron®): a cytokine that targets the IFNAR1 pathway; approved for subsets of patients with melanoma
Adjuvants
- Imiquimod: an immune adjuvant targeting the Toll-like receptor 7 (TLR7) pathway; approved for subsets of patients with basal cell carcinoma
- Poly ICLC (Hiltonol®): an immune adjuvant targeting the Toll-like receptor 3 (TLR3) pathway; approved for subsets of patients with squamous cell carcinoma
Other Immunomodulators
- Pexidartinib (Turalio™): a small molecule inhibitor of the KIT, CSF1R, and FLT3 pathways; approved for a subset of patients with tenosynovial giant cell tumor
Due to their effect on overall immune activity and their ability to stimulate immune responses, immunomodulators may cause side effects.
Side Effects
Potential side effects may vary according to the type of immunomodulator—and what exactly it targets—and may also be influenced by the location and type of cancer as well as a patient’s overall health. Sometimes the manipulation of the immune system’s brakes and gas pedals via immunomodulators may lead to overactive immune responses as well off-target responses against healthy cells, both of which may lead to side effects.
Immunomodulator-related side effects can range from mild to moderate and can become potentially life-threatening under certain circumstances. Fortunately, in most cases potential side effects can be safely managed as long as they are recognized and addressed early. Therefore, it’s extremely important that patients notify their medical care team as soon as possible if they experience any unusual symptoms during or after treatment with cancer immunotherapy. In addition, patients should always consult their doctors and the rest of their care team to gain a better and fuller understanding of the potential risks and side effects associated with specific immunomodulators.
Common side effects associated with currently approved checkpoint immunotherapies may include but are not limited to: fatigue, rash, colitis, infusion-related reactions, diarrhea, asthenia, arthralgias, constipation, decreased appetite cough, dyspnea, headache, insomnia, nausea, pain (including in the abdomen, back, and musculoskeletal system), peripheral edema, pneumonitis/radiation pneumonitis, pruritus, pyrexia, vomiting, and weight loss.
Common side effects associated with currently approved cytokine immunotherapies may include but are not limited to: bilirubinemia, chills, confusion, diarrhea, dyspnea, fatigue, fever, flu-like symptoms, headache, hypotension, myalgia, nausea, oliguria, rash, thrombocytopenia, and vomiting.