Vitiligo-like leukoderma as an indicator of clinical response to immune checkpoint inhibitors in late-stage melanoma patients

Abstract

Purpose. Although development of immune checkpoint inhibitors has revolutionized the treatment of metastatic melanoma, more than a half of treated patients experience disease progression during therapy. Cases of spontaneous vitiligo-like leukoderma have been described in melanoma patients and have been associated with a favorable outcome. This vitiligo-like leukoderma can also appear in melanoma patients undergoing immune therapies such as immune checkpoint inhibitors. However, no consensus exists about the relationship between vitiligo-like leukoderma onset and improved overall survival. Our study investigates the possible association between the onset of vitiligo-like leukoderma during immune checkpoint inhibitor treatment and a better prognosis.Methods. A non-concurrent cohort study was conducted by identifying retrospectively 280 patients who had inoperable or metastatic melanoma and had undergone immune therapy with checkpoint inhibitors in any line of treatment. Toxicities developed during therapy were evaluated.Results. Among the 280 study participants, 50% developed at least one type of toxicity, and vitiligo-like leukoderma was observed in 43 patients (15.4%). In the multivariate Cox model, a protective effect for mortality was observed for patients with vitiligo-like leukoderma development (HR = 0.23; 95% CI = 0.11-0.44, p <0.0001). In a sub-group analysis comprising only cutaneous melanoma in rst line of treatment (N=153), occurrence of vitiligo-like leukoderma was also an independent predictor factor for duration of clinical bene ts measured by time to the next treatment (HR:0.17; 95% CI:0.06-0.44). Conclusion.Our ndings indicate that onset of vitiligo-like leukoderma during melanoma treatment could be a marker of favorable outcome in patients treated with immune checkpoint inhibitors.

Multiple immune-related adverse events secondary to checkpoint inhibitor therapy in patients with advanced cancer: association with treatment effectiveness

“…Furthermore, it has been demonstrated that specific types of IRAEs exhibit a more profound correlation to treatment effectiveness and the type of these IRAEs differ across various cancer types. For example, vitiligo has been linked to treatment response in melanoma patients and thyroid dysfunction in NSCLC and renal cell carcinoma patients (24)(25)(26)(27)(28).…”

Vitiligo-specific soluble biomarkers as early indicators of response to immune checkpoint inhibitors in metastatic melanoma patients

“…These biomarkers of response to therapy would permit to better address melanoma patients towards the most efficacious treatments. In this regard, the intent of our work was the identification of predictive and/or early biomarkers of response to anti-PD-1 antibodies, taking advantages of previously identified biomarkers of an active vitiligo disease, since vitiligo-like leukoderma represents an irAE that often occurs during CPI therapy in melanoma patients and correlates with a positive outcome 48 . In fact, we confirmed also in our melanoma patient subset the association between development of leukoderma and a favorable clinical response.…”

“…Considering that leukoderma development has been described in melanoma patients receiving CPI immunotherapy and it has been associated with a positive response to therapy [25][26][27][28][29]48 , we hypothesized that immunological mechanisms like those activated in vitiligo pathogenesis could be also triggered in melanoma patients responding to CPI therapy. If this would be the case, the same biomarkers that identify vitiligo active phase could also represent biomarkers of patient response to CPI therapy.…”

Beneficial autoimmunity and maladaptive inflammation shape epidemiological links between cancer and immune-inflammatory diseases

“…In specific conditions, autoimmune diseases have been linked to improved immunosurveillance, as exemplified for autoimmune thyroiditis and thyroid cancer, 9 , 10 vitiligo and melanoma 11 , 12 or non-cirrhotic primary biliary cholangitis and cholangiocarcinoma. 13 Moreover, in preclinical models, vaccination with normal epithelial cells from the intestine or the mammary gland can induce protective immune responses against colon and breast cancer, respectively, underscoring the possibility that immune responses against (by definition) non-mutated self-antigens can participate to cancer immunosurveillance.…”