High-Dose Ipilimumab and High-Dose Interleukin-2 for Patients With Advanced Melanoma

Area of Science:

• Immunotherapy
• Oncology
• Clinical Trials

Background:

• High-dose ipilimumab (IPI) and high-dose interleukin-2 (IL-2) are approved for metastatic melanoma.
• The combination's efficacy and safety were previously unknown.
• This study evaluated the combination in advanced unresectable stage III and IV melanoma.

Observation:

• A Phase II, multicenter, open-label, single-arm trial enrolled nine patients.
• Patients received concurrent high-dose IPI and high-dose IL-2, followed by IPI maintenance.
• No prior PD-1 blockade was received by most patients.

Findings:

• One partial response (11%), four stable disease (44%), and four progressive disease (44%) were observed.
• Two patients achieved durable disease control (44+ and 50+ months).
• One-year and 2-year survival rates were 89% and 67%, respectively.
• Seven patients (78%) experienced grade 3 or 4 adverse events, all reversible.
• An increased HLA-DM:HLA-DO ratio was observed in patients with decreasing tumor burden.

Implications:

• Combination therapy with high-dose IPI and IL-2 is feasible and offers clinical benefit in advanced melanoma.
• The HLA-DM:HLA-DO ratio may serve as a novel biomarker for treatment response.
• Further studies of IL-2-based compounds with CTLA-4 blockade are warranted for patients refractory to PD-1 blockade.