The 2018 Nobel Prize in Physiology or Medicine was awarded to Tasuku Honjo and James Allison for their discoveries in cancer immunology. Professor Honjo was awarded due to his discovery of the programmed death molecule-1 (PD-1) on T cells. Professor Allison discovered another important immunosuppressive molecule: cytotoxic T-lymphocyte antigen-4 (CTLA-4). Suppression of T cell activation by PD-1 and/or CTLA-4 is considered one of the major escape mechanisms of cancer cells. Inhibition of these molecules by immune checkpoint inhibitors can successfully activate the immune system to fight cancer. Checkpoint inhibitors have brought about a major breakthrough in cancer immunotherapy, reviving the hope of curing patients with end-stage cancer, including a wide variety of cancer types. In metastatic malignant melanoma, the previous long-term survival of only 5% can now be extended to 50% with anti-PD-1 plus anti-CTLA-4 combined treatment in the latest report. More checkpoint molecules such as lymphocyte-activation gene 3 and T cell immunoglobulin and mucin domain 3 are under investigation. The achievement of Drs. Honjo and Allison in cancer immunotherapy has encouraged research into other immune-pathological diseases.

Background The association between immune-related adverse events (irAEs) and survival outcomes in patients with advanced melanoma receiving therapy with immune checkpoint inhibitors (ICIs) has not been well established, particularly in Asian melanoma. Methods We retrospectively reviewed 49 melanoma patients undergoing therapy with ICIs (anti-PD-1 monotherapy), and analyzed the correlation between irAEs and clinical outcomes including progression-free survival (PFS) and overall survival (OS). Results: Overall, the patients who experienced grade 1–2 irAEs had longer PFS (median PFS, 4.6 vs. 2.5 months; HR, 0.52; 95% CI: 0.27–0.98; p = 0.042) and OS (median OS, 15.2 vs. 5.7 months; HR, 0.50; 95% CI: 0.24–1.02; p = 0.058) than the patients who did not experience irAEs. Regarding the type of irAE, the patients with either skin/vitiligo or endocrine irAEs showed better PFS (median PFS, 6.1 vs. 2.7 months; HR, 0.40, 95% CI: 0.21–0.74; p = 0.003) and OS (median OS, 18.7 vs. 4.5 months; HR, 0.34, 95% CI: 0.17–0.69, p = 0.003) than patients without any of these irAEs. Conclusions Melanoma patients undergoing anti-PD-1 monotherapy and experiencing mild-to-moderate irAEs (grade 1–2), particularly skin (vitiligo)/endocrine irAEs had favorable survival outcomes. Therefore, the association between irAEs and the clinical outcomes in melanoma patients undergoing anti-PD-1 ICIs may be severity and type dependent.

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