Shoushtari AN, et al. - In a prospective cohort study, researchers sought to assess detailed toxic effects and time to treatment failure of patients with melanoma treated with Nivolumab plus ipilimumab (nivo?+?ipi). Observations revealed a 91% incidence of clinically significant immune-related adverse events (AEs) that resulted in frequent emergency department visits, hospitalizations, and systemic immunosuppression. Immuno-oncology trials should routinely inscribe these metrics. Patients did not tolerate 4 doses, however, less than 4 doses could exhibit clinical benefit.

Methods

• At a single tertiary cancer center, researchers examined a cohort of 64 adults with advanced or unresectable melanoma and enrolled them in an expanded access program of nivo + ipi conducted from December 2014 to January 2016.
• The patients were administered intravenous nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for up to 4 doses, followed by nivolumab (3 mg/kg) every 2 weeks or pembrolizumab (2 mg/kg) every 3 weeks until unacceptable toxic effects, disease progression, or complete response.
• For this study, they defined clinically significant immune-related AEs as Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or higher or any immune-related AEs requiring systemic steroids.
• The interval between initiating therapy and the earliest of clinical progression, new locally directed or systemic treatment other than anti–programmed cell death 1 protein (anti–PD-1) monotherapy, or death was defined as the time to treatment failure.

Results

• Researchers enrolled 64 adults with advanced or unresectable melanoma (male to female ratio, 1:1; median [range] age, 56 [22-82] years); 25 patients (39%) received all 4 doses of nivo + ipi, and 31 patients (48%) received no maintenance anti–PD-1 therapy.
• Because of toxic effects, most treatment discontinuation occurred(n = 31 [80%]).
• Time to treatment failure was similar between those who did or did not modify therapy for toxic effects among those patients who were progression free at 12 weeks.
• They noticed a clinically significant immune-related AE (median, 2/patient) in 58 patients (91%), and there were 46 patients (72%) who required systemic steroids.
• Sixteen patients (25%) required infliximab or mycophenolate for steroid-refractory immune-related AEs.
• In this study, 7 patients (11%) developed hyperglycemia, 32 patients (50%) had an emergency department visit, and 23 patients (36%) required a hospital admission related to an immune-related AE.
• A new, clinically significant immune-related AE developed in 4 of 31 patients (13%), who stopped combination therapy early for toxic effects, more than 16 weeks after the last treatment.