Michael A. Postow, MD
Different patterns of response are associated with the dosages of immunosuppressants used to manage the adverse effects of immunotherapies, said Michael A. Postow, MD, at the International Congress on Immunotherapies in Cancer™.1
Postow, a medical oncologist with Memorial Sloan Kettering (MSK) Cancer Center in New York, New York, discussed interpretive strategies and solutions for toxicity problems that commonly occur with immunotherapies. High dose (HD) and low dose (LD) steroids may may not yield inferior outcomes to avoiding use of steroids; however, there is a trend toward better outcomes based on using smaller doses of steroids rather than larger ones, Postow said.
A study of immune-related adverse events (irAEs) in patients with melanoma treated with ipilimumab (Yervoy) at MSK found that patients treated with steroids for management of irAEs had equivalent or slightly improved time to treatment failure (TTF) versus those who did not receive immunosuppressants, Postow said. Of 298 patients, 103 (35%) required corticosteroid treatment for an irAE, the majority of them (n = 78) for grade ≥3 irAEs. The major reasons for corticosteroids were diarrhea (n = 50), hepatitis (n = 22), dermatitis (n = 21), and endocrinopathies (n = 14).
Median overall survival (OS) for the full study population was 16.5 months (95% CI, 12.6-21.1) and the estimated median TTF was 5.7 months (95% CI, 5.1-6.4). In an assessment of the effect of irAEs on OS and TTF, investigators found no difference in either measure when patients were stratified by the presence or absence of irAEs of any grade or by the administration of systemic corticosteroids to treat an irAE.2
Postow also noted a retrospective analysis of nivolumab (Opdivo) monotherapy in patients with advanced melanoma, designed to assess the safety profile of the agent and the management of irAEs. This found that use of immune modulators did not result in significantly different overall response rates: 29.8% (95% CI, 21.6%-39.1%) for those receiving corticosteroids (n = 114) versus 31.8% (95% CI, 27.6%-36.3%) for those who did not (n = 462).3
However, he said, a retrospective study evaluating HD steroids versus LD steroids in the treatment of ipilimumab-induced hypophysitis did find distinct survival patterns relative to the levels of dosage used. Among 98 patients with melanoma with ipilimumab-induced hypophysitis, OS and TTF were significantly longer in the LD group compared with the HD group. Median OS and TTF were not reached in the LD group and were 23.3 and 11.4 months, respectively, in the HD group. HD was identified as any dose larger than 7.5 mg daily of prednisone (Table
Investigators also found that all patients who had hypophysitis had superior OS compared with those who did not have hypophysitis (median OS, 28.2 vs 9.5 months; P
= .0003). In addition, radiologic and endocrinologic outcomes and symptom resolution were not different between the LD and HD groups.4
The study was a helpful start in addressing the question of whether patients would do better if you didn’t treat their irAEs with immunosuppressants, a question that’s inherently difficult to resolve because patients often receive immunosuppression for adverse events, Postow said.