Spotlight: What Are the Side Effects of Cancer Immunotherapies?

Spotlight: What Are the Side Effects of Cancer Immunotherapies?

Immuno-oncology uses the body’s own natural defenses to combat cancer. Researchers are currently looking into several different mechanisms for training the immune system to attack cancer and bolstering its ability to kill cancerous cells. This approach to cancer treatment is a major break from the traditional treatment modalities, such as chemotherapy and radiation, which kill both cancerous cells and healthy body cells. While medical researchers have devised ways of focusing these treatments to minimize the deleterious effects on healthy tissues, they still cause very serious side effects in patients.

Several questions about immuno-oncology and its efficacy continue to exist, including what sorts of side effects immunotherapy will cause. While these side effects are largely expected to be milder than those of traditional treatments, patients may still face some serious treatment-associated complications.

Some of the Side Effects Associated with Approved Treatments

Some immuno-oncology drugs have already received approval for use in cancer treatment, so the side effects of these substances have been extensively researched. Because immunotherapy agents work through mechanisms that are radically different from radiation or chemotherapy, the side effects are distinct. This fact is important to consider because immunotherapies are generally offered in concert with standard-care treatments, so they create extra burdens on patients who choose to take them.

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Image courtesy James Palinsad | Flickr

One of the main ways that investigators have fought cancer through immunotherapy is by inhibiting natural checkpoints in the body. Immune checkpoints keep the system from attacking cells that are supposed to be in the body. However, cancer cells take advantage of these checkpoints to prevent the immune system from identifying them as foreign cells that need to be destroyed. When these checkpoints are disabled, the brakes are taken off of the immune system so that it can attack cancer cells. However, without checkpoint restraint, the system can also attack healthy tissues, thus producing effects similar to the symptoms of an autoimmune disease.

Research has found that immunotherapies are generally well tolerated by patients with no hair loss or blood cell abnormalities that could potentially result from such treatment. However, other side effects have emerged, the most common of which is fatigue. Patients may also experience fevers, chills, and nausea, as well as local reactions at sites where the drugs are administered.

Some of the approved checkpoint inhibitors currently being administered to patients include Ipilimumab, nivolumab, and pembrolizumab. These drugs can help patients with kidney and lung cancer, as well as those with melanoma. While the previously mentioned side effects are controllable, patients may experience more serious issues, such as pancreatitis, hepatitis, colitis, and pneumonitis. Some patients also develop endocrine disorders, such as thyroid abnormalities and adrenal insufficiencies, as well as severe skin rashes. Doctors closely monitor patients who receive these drugs, so that they can control adverse symptoms immediately. To soothe inflammatory overreactions, for example, they can administer corticosteroids and antihistamines.

 Side Effects of Other Common Approaches to Cancer Immunotherapy

Outside of the approved checkpoint inhibitors, researchers are looking into several other immuno-oncology techniques for treating cancer. For example, some scientists are investigating the potential of cancer vaccines. These therapies involve the targeting of antigens that are commonly found on tumor cells but only rarely exist on normal cells. Because the treatments are so specific, vaccines have demonstrated very low toxicity. The most common side effects of Provenge (the only approved cancer vaccine currently on the market) are chills and back pain. However, these side effects only occur in about 2 percent of patients.

Another approach to immuno-oncology involves cytokines. Recombinant human interferon alfa was approved for the treatment of hairy cell leukemia in 1992, and six years later, interleukin-2 was approved for use in the treatment of renal cell carcinoma and melanoma. Both of these treatments frequently result in serious, often life-threatening, side effects, such as vascular leak syndrome. Patients often report headache and myalgias, as well as fever and fatigue that can be dose-limiting. Nearly half of patients develop depression while on the drugs, and neuropsychiatric symptoms are sometimes reported with human interferon alfa. Other common side effects include diarrhea, anorexia, hyper- and hypothyroidism, and thrombocytopenia. Interleukin-2 can lead to pleural effusions, kidney failure, hypotension, and pulmonary edema.

Some cancer immunotherapies fall under the umbrella of adoptive cell therapies, which are derived from tumor-infiltrating lymphocytes in certain cancers. These therapies are engineered using the patient’s own cells, and they have proven effects against synovial sarcoma, cervical cancer, and metastatic melanoma. In certain cases, these therapies have caused life-threatening autoimmunity that requires expert management. In addition, some patients develop cytokine release syndrome. In preparation for these therapies, patients undergo chemotherapy, which can cause sepsis and life-threatening immunosuppression. The toxicities that result from these treatments can be controlled using corticosteroids and alemtuzumab.

The Future of Immuno-Oncology Side Effects

Researchers are actively looking for biomarkers that could identify likely toxicities from these various cancer immunotherapies. While no biomarkers have yet been identified, it is possible that oncologists will be able to predict side effects in the future and treat them prophylactically.

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