ASCO, NCCN Advise on Immune Checkpoint Inhibitor AEs

The American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) have released new guidelines to help clinicians assess and manage side effects related to immune checkpoint inhibitors.

“With rapidly increasing use of immune checkpoint inhibitors, it is imperative that clinicians are knowledgeable about their unique toxicity profiles. These new guidelines from ASCO and NCCN will help our community continue to provide the highest quality of care to all patients as they incorporate these agents into routine care,” said Clifford A. Hudis, MD, ASCO Chief Executive Officer.

The guidelines were published on February 15, 2018 in Journal of Clinical Oncology and at NCCN.org

The use of checkpoint inhibitors and combinations continues to expand beyond melanoma, Hodgkin lymphoma, and lung, liver, kidney, and bladder cancers to more indications. However, checkpoint inhibitors may be associated with unique toxicities that involve multiple body organs. Because of the rapid introduction of checkpoint inhibitors, many clinicians may not have experience in recognizing and treating these side effects.

“The real winners here are patients whose health care teams now have high quality, collaborative guidelines from ASCO and NCCN to minimize treatment toxicity and optimize outcomes,” said Robert W. Carlson, MD, Chief Executive Officer of NCCN. “While novel immunotherapies allow for life-extending therapy for selected forms of cancer, their success is associated with potentially substantial toxicity. These side effects are different from other forms of anticancer therapy and require rapid and appropriate recognition and treatment.”

Immunotherapy-related side effects can occur at any time and can affect any organ. The most common ones are rash, diarrhea, reduced levels of thyroid hormone, and fatigue. More severe side effects can lead to inflammation of the lung, intestines or liver, hormonal abnormalities, and kidney, heart, or neurologic problems.

“If you take the brakes off the immune system and allow it to attack cancer, it may also attack the healthy tissue in a patient’s body,” said John A. Thompson, MD, codirector, Seattle Cancer Care Alliance Melanoma Clinic, Fred Hutchinson Cancer Research Center. Dr. Thompson is chair of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Panel on Management of Immunotherapy-Related Toxicity, and cochair of the expert panel that developed the ASCO guideline. “Fortunately, most of the side effects are reversible, but early recognition and proper treatment are critical.”

The new guidelines stem from a systematic review of 204 eligible publications and an informal consensus process. They pertain only to immune checkpoint inhibitors, not to other types of immunotherapy.

Key recommendations include:

• For mild (grade 1) toxicities, checkpoint inhibitors can be continued with close monitoring, with the exception of neurologic and some hematologic toxicities.
• For moderate (grade 2) toxicities, checkpoint inhibitors should be held until symptoms and/or lab values revert to grade 1 levels or lower. Corticosteroids may be offered.
• For severe (grade 3) toxicity, patients should receive high-dose corticosteroids for at least 6 weeks. Extreme caution is recommended when restarting immunotherapy after a patient has experienced grade 3 toxicity.
• Very severe (grade 4) toxicity necessitates stopping checkpoint inhibitor therapy permanently.
• Consult the guidelines directly for more specific recommendations depending on which organ is affected.