Safety of anti-PD1 in the treatment of melanoma: A survey in 90 patients treated in a French University Hospital

Introduction Metastatic melanoma is an aggressive disease with a 16% 5-year survival rate and poor response to most standard chemotherapies. Immune checkpoint inhibitors pembrolizumab and nivolumab, two anti-programmed-death-1 (PD-1) drugs, have been approved for the treatment of advanced melanoma. Survival results reported to date are very promising, but several adverse effect (AE), such as immunological AE, are expected. The aim of this study is to report the rate of AE related to these drugs in 90 patients treated for malignant melanoma. Methods An observational prospective study was conducted in 90 consecutive patients treated for malignant melanoma in a French university referral hospital. A standardized questionnaire was developed to collect data. Results A total of 90 patients were included (51 men and 39 women) between January 2014 and June 2016. The median of age was 67.0 years (IQR: 50.3–75.3 years). Fifty-three patients were treated by nivolumab and thirty-four by pembrolizumab. Mutated BRAF was significantly more frequent in patients treated with nivolumab (48.2% vs. 17.6%, P  = 0.004). Cutaneous (30%), hepatic (15.6%), gastrointestinal (12.2%) and renal (6.7%) AE occurred in 59 patients (65.6%). One patient developed a Vogt-Koyanagi Harada syndrome after 15 months of successful pembrolizumab treatment. Severe (grade 3–4) AE (17% of AE) occurred in 10 patients and motivated discontinuation ( n  = 3) or withdrawal of anti-PD1 ( n  = 2). Only 3 (30%) of these last cases were reported to the pharmacovigilance center. Conclusion The rate of AE related to pembrolizumab and nivolumab in this study is similar to those previously reported in the literature. As severe AE were under-reported to the pharmacovigilance center, physicians need to be made aware of the importance of reporting AE of these drugs, in particular because the length of treatment can lead to new adverse effects detection.