Real-World Impact of Low-Grade Toxicities to Adjuvant Pembrolizumab in Stage III Melanoma.

Purpose: Primary malignant melanoma is a curable disease, with surgical resection being the gold standard of treatment. For stage III melanoma, which poses a high risk of recurrence, adjuvant checkpoint inhibitors are used to reduce the risk of relapse. However, adjuvant treatment carries a risk of immune-related adverse events that can significantly impact on quality of life. Although the impact of grade 3 to 4 toxicities has been well characterized, the impact of lower-grade toxicity in this setting has not been as robustly discussed in the literature.

Methods: We gathered retrospective data on patients with stage III melanoma who underwent adjuvant pembrolizumab treatment between December 2019 and December 2022 from two sites (Belfast City Hospital and Royal Preston Hospital). This included information on toxicity on the basis of Common Terminology Criteria for Adverse Events grading (version 5), treatment discontinuation, hospital admission, toxicity treatments, and disease progression.

Results: Data were collected on 142 patients. 67 (47%) completed a 1-year course of adjuvant pembrolizumab. Median recurrence-free survival was 36.2 months. One hundred (70%) experienced treatment-related toxicity, of whom 72 (51%) had only low-grade toxicity (grade 1 to 2). In patients with only low-grade toxicity, 15% were hospitalized, 31% had treatment stopped because of toxicity, and 33% required immunosuppression treatment. The rate of early treatment discontinuation was higher among patients age 65 years or older compared with patients younger than 65 years (66% v 38%, P < .001).

Conclusion: In addition to the impact of grade 3 to 4 toxicities, there is a substantial burden of low-grade toxicity in patients undergoing adjuvant pembrolizumab treatment for stage III melanoma. Clinicians should discuss its potentially significant impact with patients and prepare to support them through these effects.