Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients

SIMPLE SUMMARY: Elderly cancer patients over the age of 80 years represent a growing population; these are notably melanoma patients since 25% of cases are diagnosed after 75 years of age. Establishing the best therapeutic strategies for older patients with melanoma is a challenge since this subpopulation has poor disease-specific outcomes, partly due to age-related variations in therapeutic management. Regarding mono-immunotherapy, either with anti-CTLA-4 or anti-PD-1, several studies have shown similar tolerability outcomes in older and younger patients. However, there are limited data in very elderly patients, especially those treated with immunotherapy combinations. The aim of this multicenter retrospective study is to analyze the prescribing patterns and the safety profile of nivolumab combined with ipilimumab in a cohort of octogenarian and nonagenarian melanoma patients in a real-life setting. The results indicate that the prescribing patterns are very heterogeneous in patients aged over 80 years old, highlighting the lack of clear therapeutic guidelines in the elderly population. In this cohort, the toxicity data did not show a high frequency of severe immune-related adverse events. ABSTRACT: Data regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3–93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question.