BACKGROUND: Immunotherapy with checkpoint inhibitors (CPIs) is an emerging anticancer treatment strategy, which may cause a variety of skin reactions. In this study, we sought to analyze and classify the cutaneous side effects (CSE) of the CPIs nivolumab, pembrolizumab, and ipilimumab with respect to prevalence, type, and severity, and to review their potential interference with CPI immunotherapy. METHODS: In this retrospective analysis, medical records were analyzed with respect to incidence, type, and severity of CSE in patients on CPI immunotherapy for cancer. The implications for immunotherapy maintenance were scrutinized. RESULTS: From 2012 to 2019, 352 consecutive patients were treated with CPIs for cancer, of which 46 patients (13.1%) experienced CSE. The incidence of CSE was less with nivolumab (n = 16; 9.5%) and pembrolizumab monotherapy (n = 9; 9.6%) as compared to ipilimumab (n = 10; 23.3%) and combination therapy (n = 11; 23.9%); P < 0.05. Skin toxicity could be stratified by rash/eczema (n = 28; 60.9%), autoimmune (n = 8; 17.4%, vitiligo n = 5, lichen sclerosus n = 2, psoriasis guttata n = 1), lichenoid reaction (n = 5; 10.9%), pruritus (n = 4; 8.7%), and a miscellaneous group (n = 3; 6.5%). The limited severity grades of CSE caused immunotherapy disruption in only three (0.9%) cases. Interestingly, 80% of melanoma patients who developed vitiligo during immunotherapy had stable disease or disease remission. CONCLUSION: CPIs in cancer patients may result in a distinct set of CSE, with drug rash and eczematous rash being the most common. CTLA-4 blocker ipilimumab and combination therapy are more prone to elicit skin toxicity than the PD-1 inhibitors nivolumab and pembrolizumab, although this rarely interferes with the continuation of immunotherapy.
BACKGROUND: Immunotherapy with checkpoint inhibitors (CPIs) is an emerging anticancer treatment strategy, which may cause a variety of skin reactions. In this study, we sought to analyze and classify the cutaneous side effects (CSE) of the CPIsnivolumab, pembrolizumab, and ipilimumab with respect to prevalence, type, and severity, and to review their potential interference with CPI immunotherapy. METHODS: In this retrospective analysis, medical records were analyzed with respect to incidence, type, and severity of CSE in patients on CPI immunotherapy for cancer. The implications for immunotherapy maintenance were scrutinized. RESULTS: From 2012 to 2019, 352 consecutive patients were treated with CPIs for cancer, of which 46 patients (13.1%) experienced CSE. The incidence of CSE was less with nivolumab (n = 16; 9.5%) and pembrolizumab monotherapy (n = 9; 9.6%) as compared to ipilimumab (n = 10; 23.3%) and combination therapy (n = 11; 23.9%); P < 0.05. Skin toxicity could be stratified by rash/eczema (n = 28; 60.9%), autoimmune (n = 8; 17.4%, vitiligo n = 5, lichen sclerosus n = 2, psoriasis guttata n = 1), lichenoid reaction (n = 5; 10.9%), pruritus (n = 4; 8.7%), and a miscellaneous group (n = 3; 6.5%). The limited severity grades of CSE caused immunotherapy disruption in only three (0.9%) cases. Interestingly, 80% of melanomapatients who developed vitiligo during immunotherapy had stable disease or disease remission. CONCLUSION:CPIs in cancerpatients may result in a distinct set of CSE, with drug rash and eczematous rash being the most common. CTLA-4 blocker ipilimumab and combination therapy are more prone to elicit skin toxicity than the PD-1 inhibitors nivolumab and pembrolizumab, although this rarely interferes with the continuation of immunotherapy.