Real world experience in low-dose ipilimumab in combination with PD-1 blockade in advanced melanoma patients.

Dual immune-checkpoint blockade with the anti-PD-1 antibody nivolumab (1 mg/kg) and standard-dose ipilimumab (3 mg/kg) is the mainstay of immunotherapy in advanced melanoma and it is approved since 2016. However, severe side effects (grade 3/4) occur in up to 60% of the patients. Recently, clinical trials have shown similar anti-tumor activity with a more favorable toxicity profile in patients treated with low-dose ipilimumab (1 mg/kg) and standard-dose pembrolizumab (2 mg/kg). In this study we report on the real-world experience of this dosing regime in advanced melanoma patients not eligible for clinical trials. A total of 33 patients with metastatic melanoma (24 with cutaneous and 9 with uveal melanoma) were assessed, retrospectively. Brain metastases were present in 33% of the patients and lactate dehydrogenase was elevated in 70%. Overall response rates were 38% and 0% in cutaneous melanoma and uveal melanoma respectively. Median overall survival was not reached in cutaneous melanoma and was 18 months in uveal melanoma. In 18% of the patients at least one treatment-related severe adverse event was observed. Our observation that the combination of standard dose pembrolizumab and low-dose ipilimumab has a favorable toxicity profile yet anti-tumor activity comparable to the approved standard-dose combination regime in advanced patients not suitable for enrollment in clinical trials is encouraging.