Study Finds Immunotherapy Causes Chronic Side Effects

A recent study has found chronic immune-related side effects are common in patients with skin cancer who are treated with postsurgical Opdivo (nivolumab) or Keytruda (pembrolizumab), although for some individuals, these toxicities resolve by the 18-month mark.

In the study, researchers analyzed data from 318 patients who were treated with Opdivo or Keytruda after undergoing surgery for advanced or metastatic melanoma. Findings showed 147 patients (46.2 percent) experienced at least one chronic (lasting three months or longer) immune-related side effect. This included 74 grade 2 or higher side effects and six grade 3 through 5 (moderate, severe or fatal). All side effects were symptomatic. Common immunotherapy side effects that sometimes became chronic included adrenal insufficiency, arthritis or joint pain, skin inflammation, thyroid issues and colitis/diarrhea.

At a longer follow-up (average of 34.7 months), 54 patients (36.7 percent) experienced resolution of their chronic side effects, with an average of 11.2 months between ending their immunotherapy treatment and having their toxicity resolve. For those still experiencing side effects at the long-term follow-up, 59.1 percent had grade 2 or higher side effects, while 44.1 percent were symptomatic and 25.8 percent were using therapeutic steroid treatment.

Among the 48 patients who experienced chronic side effects, 32.7 percent experienced disease recurrence, including 18 cases (12.2 percent) of regional recurrence and 30 (20.4 percent) of metastatic recurrence, meaning the cancer spread to another part of the body. Additionally, some patients (32.4 percent) experienced a flare of the toxicity when they were retreated with immunotherapy.

“(Immunotherapy drugs) targeting … PD-1/PD-L1 prolong recurrence-free survival when used as adjuvant therapy. … Anti–PD-1 also causes widespread T-cell activation and results in autoimmune side effects involving multiple organs, termed immune-related adverse events,” the researchers wrote. “While most severe (immune-related adverse events) are acute and resolve with glucocorticoids, we recently reported that up to 43 percent of (immune-related adverse events) persist for at least 12 weeks following therapy cessation in patients with melanoma treated with adjuvant anti–PD-1.”