Adjuvant use of peginterferon alfa-2b (pegIFN) has been shown to improve progression-free survival (PFS) in patients with resected stage III melanoma.1 Ipilimumab (IPI) is approved as a single agent for patients with metastatic melanoma (MM) on the basis of increased overall survival (OS).1 Kudchadkar and colleagues (ASCO 2014; Abstract 9098) reported updated results of a phase 1B study in which IPI (3 mg/kg every 3 weeks x 4 doses) was combined with pegIFN (3 mcg/kg weekly) in patients with unresectable stage IIIB, IIIC, and IV melanoma. PegIFN was given for a maximum of 3 years or until disease progression, unacceptable toxicity, or patient withdrawal.
To date, 31 patients (18 men and 13 women) have been treated with IPI and pegIFN, including 23 cutaneous primaries, 6 unknown primaries, and 2 acral melanomas. Their median age was 61 years.
Among 30 patients evaluable for response, there was 1 confirmed complete response (CR), 13 confirmed partial responses (PR), and 3 confirmed stable disease, resulting in a 47% overall response rate and a 57% disease control rate. Six-month PFS was 56%. Median OS was 16.6 months, and 1-year OS was 56%. There was no significant change in the presence of autoantibodies between responders and nonresponders in the evaluable patients. However, all 5 cases of vitiligo were associated with response, with 4 PRs and 1 CR.
Toxicities associated with pegIFN dosed at 3 mcg/kg weekly resulted in dose reductions for 7 patients. Grade 3 events leading to dose reductions included nausea and vomiting, leukopenia, dehydration, and hyponatremia. After observing these toxicities, subsequent trial enrollees received pegIFN at a dose of 2 mcg/kg weekly. Among these patients, grade 3/4 treatment-related events included pneumonitis, nausea/vomiting, rash, pruritus, fatigue, neutropenia, and diarrhea.
This study suggests that pegIFN combined with IPI in MM results is active, with a response rate of 47% to date. PegIFN (2 mcg/kg weekly) with IPI (3 mg/kg every 3 weeks x 4) is well tolerated, with grade 3 rash appearing to correlate with response. Kudchadkar and colleagues concluded that this immunotherapy combination warrants further exploration in MM.
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