Ipilimumab Plus Nivolumab Sustains Efficacy Among Patients With Asymptomatic Melanoma Brain Metastases

According to long-term follow-up results from a phase 2 study, ipilimumab plus nivolumab demonstrated long-term efficacy among immunotherapy-naive patients with asymptomatic melanoma brain metastases. 

“Patients with melanoma brain metastases respond well to immunotherapy, but long-term comparative survival data are scarce,” wrote Georgina Long, PhD, Melanoma Institute Australia, Sydney, Australia, and coauthors. Here, “we aimed to assess the efficacy of ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases at 7 years.”

In this open-label study, researchers enrolled 79 patients who had not received prior lines of brain-directed therapy. Patients were randomized on 5-to-4 basis to receive either 3 mg/kg of intravenous ipilimumab plus 1 mg/kg of nivolumab every 3 weeks for 4 doses followed by an additional 3 mg/kg of nivolumab every 2 weeks (n = 36), or 3 mg/kg of intravenous nivolumab every 2 weeks (n = 27). There was an additional, non-randomized cohort, including patients who had received previous brain-directed therapy, or with neurological symptoms or leptomeningeal disease, treated with the nivolumab monotherapy regiment (n = 16). The primary end point was 7-year intracranial response. Key secondary end points included intracranial progression-free survival (PFS), overall survival (OS), and safety. 

At a median follow-up of 7.6 years, intracranial responses occurred in 51% of patients in the ipilimumab-nivolumab arm and 20% of patients in the randomized nivolumab monotherapy arm. Intracranial PFS rate at 7 years was 42% in the ipilimumab-nivolumab arm and 15% in the randomized nivolumab monotherapy arm and 7-year OS rate was 48% and 26%, respectively. Safety was consistent with prior results. At the time of analysis, 50 patients had died, including 18 in the ipilimumab-nivolumab arm, 18 in the randomized nivolumab monotherapy arm, and 14 in the non-randomized arm. 

“Our findings suggest that ipilimumab plus nivolumab maintains efficacy to at least 7 years in patients with active asymptomatic brain metastasis,” concluded Dr Long et al. “Upfront ipilimumab plus nivolumab should be the standard of care for patients with melanoma brain metastasis.” 

Source: 

Long GV, Atkinson V, Lo SN, et al. Ipilimumab plus nivolumab versus nivolumab alone in patients with melanoma brain metastases (ABC): 7-year follow-up of a multicentre, open-label, randomised, phase 2 study. Lancet Oncol. Published online: February 17, 2025. doi: 10.1016/S1470-2045(24)00735-6