Factors of Ipilimumab/Nivolumab Success in Metastatic Melanoma Identified

This new analysis of combination treatment with ipilimumab and nivolumab identified factors likely to lead to therapeutic success with the combination.

A new analysis of the use of ipilimumab (Yervoy) and nivolumab (Opdivo) to treat patients with advanced metastatic melanoma found a lower real-world overall survival (OS) rate than previous studies. However, it also identified factors that may boost an individual’s chance of success with the therapy.

As immune checkpoint inhibitors (ICIs) have become an important part of melanoma treatment, the strategy of combining anti–CTLA-4 agents, like ipilimumab, with anti–PD-1 agents, like nivolumab, has gained traction. However, the study authors noted that many patients do not respond to ICIs and there is a lack of clear biomarkers that can be used to predict which patients will and will not respond, as well as which types of therapy would be ideal.

In a new study in Clinical and Translational Oncology, the investigators looked back at OS and related biomarkers in a cohort of 44 patients who had advanced melanoma and received at least 1 dose of an ipilimumab/nivolumab regimen between 2016 and 2020. All of the study enrollees were patients at the same institution.

“In addition, we evaluated the baseline clinical characteristics, molecular variables, and peripheral blood laboratory values to determine the [OS] in this cohort and explore biomarkers associated with clinical benefit,” they wrote.

Most of the patients in the study (86.4%) had cutaneous melanoma, about half each had BRAF mutant cancers and high lactate dehydrogenase (LDH) values at presentation. Twenty-three patients had at least 3 disease sites, and 10 patients had brain metastases.

Most of the patients (63.6%) were treatment naïve, 9 patients had received BRAF and MEK inhibitors, 5 had been on anti–PD-1 therapy, and 2 had received other therapies.

With a median follow-up of 37.7 months, the investigators calculated a median OS of 21.1 months (95% CI, 8.2-not reached). When the authors separated out patients with central nervous system (CNS) metastases, they found an overall response rate (ORR) of 39.4% among patients without CNS metastases and a 10% ORR among those with CNS metastases; there was no difference in median OS.

“This value is lower than that of previous studies likely because of the inclusion of 22% of patients with brain metastases, most with > 3 brain lesions, half of whom required corti- costeroid treatment,” the authors wrote.

When they performed a multivariate analysis, they found patients with Eastern Cooperative Oncology Group scores of zero, those with normal LDH levels, those without liver metastases, and those with neutrophil-to-lymphocyte ratios less than 5 had significantly longer OS. These factors were then used to classify patients into 3 prognostic risk groups.

“The model proposed allowed the identification of patient subgroups with different prognoses following ipilimumab-plus-nivolumab treatment, with 31.8% of patients presenting favorable values in all 4 factors, and the median OS was not reached,” they said. “In contrast, the prognosis was poor in individuals with 0-1 favorable factors, presenting a median OS of 2.2 months after initiating the ipilimumab-plus-nivolumab regimen.”

The investigators said their study offers potential new biomarkers that could be used to guide treatment decisions, although they said their findings would need to be verified in future prospective trials.


Vila CM, Moreno FA, Estébanez MM, et al. Exploratory analysis of clinical benefit of ipilimumab and nivolumab treatment in patients with metastatic melanoma from a single institution. Clin Transl Oncol. Published online August 22, 2021. doi:10.1007/s12094-021-02692-9

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