Immunotherapy drugs fall into varying classes, each carrying its own mechanism of action and anticipated side effects. Although some side effects of immunotherapy may appear similar to those of chemotherapy (e.g., diarrhea, fatigue), they actually result from a totally different mechanism—meaning they require a different approach to management. Treating immunotherapy side effects as you would chemotherapy effects would likely result in patient harm.

Active Immunotherapies

Some classes of immunotherapy actively engage the immune system to recognize and destroy cancer cells specifically, and they may even enable the immune system to remember cancer cells. As such, some treatments are administered only one time, and then the immune system will recognize cancer in the future.

Chimeric antigen receptor (CAR) therapy: With two recent U.S. Food and Drug Administration (FDA) approvals for the treatment of hematologic malignancies, much has been learned about CAR therapy, where a patient’s T cells are genetically engineered to recognize and destroy cells expressing a specific antigen. Approved therapies exploit the CD19 antigen commonly associated with leukemia and lymphoma.

The most well-documented side effect is cytokine release syndrome. Patients should be vigilantly monitored for fever, hemodynamic changes, and laboratory abnormalities. Intervention requires ruling out an infectious cause while rapidly providing antipyretics, IV fluids, and potentially mechanical ventilation and renal support.

Cancer vaccines: Cancer vaccines also exploit tumor-associated antigens to train the immune system to target and kill cancer cells. Therapeutic cancer vaccines either delay or stop cancer cell growth, shrink the tumor, and prevent tumor growth. They work by presenting the immune system with antigens it will recognize as foreign or dangerous. Vaccines often include the administration of an adjuvant such as filgrastim to stimulate the immune system.

Some cancer vaccines are administered subcutaneously, whereas others require IV administration. Premedications are recommended to prevent hypersensitivity reactions. Patients commonly report flu-like symptoms; other effects include myalgias, nausea and vomiting, and injection site pain.

Passive Immunotherapies

Other immunotherapy classes are passive; rather than inducing cancer cell death, they optimize the immune system to be more effective in the way it surveys for cancer cells. These classes typically require routine and frequent administration because they do not create long-lasting immunity.

Checkpoint inhibitors: Checkpoint inhibitors have exploded on the cancer treatment scene with more than five agents currently approved for multiple cancer sites. PD-1, PD-L1, and CTLA-4 are common immune checkpoints that normally stop immune activity. Inhibiting these checkpoints allows the immune system, T cells specifically, to stay in overdrive, survey for cancer cells, and mount an immune response to attack cancer cells.

The agents may be associated with infusion reactions. Although relatively well tolerated, given the mechanism of action for these agents, most side effects are immune-related and result from an overactive immune system. Commonly reported immune-related adverse events (irAEs) include dermatitis, colitis, pneumonitis, and endocrinopathies, but any body system is subject to impact. Conduct vigilant assessments and use systemic corticosteroids when implicated. The American Society of Clinical Oncology and the Society for Immunotherapy of Cancer recently published checkpoint inhibitor-related irAE management guidelines.

Monoclonal antibodies: More than a dozen monoclonal antibodies (mAbs) are currently FDA approved, transforming the approach to pharmacologic cancer treatment. MAbs seek out and attach to tumor-associated antigens on the surface of tumor cells, essentially becoming a beacon for the immune system to recognize foreign cells. Some mAbs are bound to other anticancer agents and deliver the agent directly to the tumor, leaving healthy cells untouched.

MAbs are developed in a laboratory and derived from human antibodies, animal antibodies, or a combination. For that reason, infusion-related reactions are associated with mAbs. Premedication is a common part of the treatment plan to prevent these reactions, but institutions should have a management plan in place in the event of an emergency during administration of these agents.

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