Abstract
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.
Highlights
In recent years, monoclonal antibodies blocking the inhibitory programmed cell death 1 pathway (PD-1/PDL1) and the cytotoxic T lymphocyte associated protein 4 (CTLA-4) have significantly impacted the treatment of advanced melanoma
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 were included in this study (Figure 1), 23 patients with cutaneous melanoma, 9 patients with uveal melanoma and 1 patient with melanoma of unknown primary (MUP; Table 1 )
Summary
Monoclonal antibodies blocking the inhibitory programmed cell death 1 pathway (PD-1/PDL1) and the cytotoxic T lymphocyte associated protein 4 (CTLA-4) have significantly impacted the treatment of advanced melanoma. In melanoma the low-dose ipilimumab (1 mg/kg) protocol was investigated in the KEYNOTE-029 (NCT02089685) and CheckMate 511 (NCT02714218) trials. Reducing the toxicity by the sequential administration of Ipilimumab (3 mg/kg, four doses), followed by nivolumab (3 mg/kg) versus vice versa has been investigated (Checkmate 064 trial) [14]. The rate of grade 3/4 AEs between both cohorts was high with 63% in the nivolumab followed by ipilimumab group and 50% in the reverse sequence. Reducing the number of ipilimumab infusions was investigated in a cohort of 40 patients with short-term ipilimumab (2 cycles) followed by PD-1 blockade and induced treatment-related grade 3/4 AEs in only 38% of patients with an ORR of 55% [15].
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