Benefit of immune checkpoint inhibitors as adjuvant treatment for acral melanomas.

[BACKGROUND] Solar factors play no role in the development of acral melanoma (AM). AM is characterized by low cumulative solar damage (low CSD). Responses to immunotherapy are correlated with mutational load, which, in turn, is correlated with high cumulative sun damage (CSD). This suggests that AM patients may have poor responses to immunotherapy. The clinical benefit and safety profile of adjuvant immunotherapies in AM treatment have not been fully investigated.

[OBJECTIVES] To investigate whether the use of adjuvant immunotherapy for treating patients with AM in Stages IIb, IIc, III and IV NED (no evidence of disease) improves distant metastasis-free survival.

[METHODS] Among the 1005 AM patients in the RIC-Mel melanoma database, 64 AM patients who were treated with adjuvant immunotherapy were included in this study. We then calculated a propensity score to make the adjuvant immunotherapy-treated (n = 64) group and the untreated group (n = 64) comparable in all respects.

[RESULTS] The use of adjuvant immunotherapy for treating AM offers no clear benefit in terms of relapse-free survival or distant metastasis-free survival (RFS: HR = 0.84 [0.534, 1.324, 95% CI] and DMFS: HR = 0.94 [0.565, 1.562, 95% CI]). Among the AM patients who received adjuvant immune checkpoint inhibitors (ICI), 18.8% experienced severe (Grades 3-4) immune-related adverse events.

[CONCLUSIONS] The benefit-risk balance must be carefully weighed, including the relapse-free survival (RFS), distant metastasis-free survival (DMFS) and rate of severe immune-related adverse events (irAE) occurrence. Other therapeutic strategies should be investigated in larger studies to confirm the potential limited clinical benefit of this treatment strategy.