John Theurer Cancer Center Participates in Multicenter Study Showing Treatment of Melanoma Immunotherapy Side Effects Does Not Impair Patient Outcomes

Researchers from Hackensack Meridian John Theurer Cancer Center and Lombardi Comprehensive Cancer Center at Georgetown University, an NCI consortium, conducted a multicenter study showing that the treatment of immune-related side effects in people with advanced melanoma receiving immunotherapy does not impair overall survival or increase their risk of recurrence. The study was reported in the journal Cancer, a publication of the American Cancer Society.

"Our findings support the use when necessary of medications to manage immune-related adverse events in people receiving immunotherapy for inoperable or metastatic melanoma," explained Andrew Pecora, MD, co-chief of the Division of Skin Cancer and Sarcoma, who led JTCC's participation in the study.

Immunotherapies called checkpoint inhibitors have revolutionized the treatment of advanced melanoma and other solid tumors. They work by taking the brakes off the immune response, boosting the power of immune cells to detect and destroy cancer cells. Some inhibit a checkpoint protein called CTLA-4 (such as ipilimumab) and others block the action of a protein called PD-1 (such as nivolumab and pembrolizumab). These medications are called checkpoint inhibitors.

Some patients experience immune-related side effects from checkpoint inhibitors, such as chills, fever, headache, and flu like symptoms, which may be treated with immunosuppressive drugs like steroids (such as prednisone) or other medications. Few studies, however, have investigated the effects of immunosuppressive medications on the effectiveness of immunotherapy, and their impact on long-term anti-tumor immunity has been uncertain.

In this retrospective study, researchers looked at outcomes among 370 patients, many treated at John Theurer Cancer Center or Georgetown Lombardi Comprehensive Cancer Center, who had received immune checkpoint inhibitors for stage III or IV melanoma. They examined the effects of immunotherapy type, incidence of immune-related side effects, and immunosuppressive treatment of those side effects on overall survival and progression-free survival (the time it took for a cancer to grow or return). Overall, immune-related side effects occurred in 57% of the patients, and in 23% of patients, those side effects were moderate to severe. Thirty-seven percent of patients received steroids and 3% received other immunosuppressive medications.

Overall survival was shortest among those who did not experience immune-related side effects and longer among patients who received steroids for immune-related side effects, with or without other immunosuppressive medications. Similar results were observed for those who received only anti-PD-1 immunotherapy as well as those who received both anti-CTLA-4 and anti-PD-1 treatments.

Prior studies have also shown that the development of immune-related side effects may indicate that the immune system has become activated by immunotherapy and is primed to recognize and kill cancer cells. "These data also suggest that the presence of immune-related side effects and their management using steroids and other immunosuppressive agents are predictive markers of the effectiveness of immunotherapy," Dr. Pecora added.