Dr Tarhini on Hogh-Dose Bolus IL-2 With Ipilimumab Followed by Nivolumab in Melanoma

Ahmad Tarhini, MD, PhD, director, Cutaneous Clinical and Translational Research, leader, Neoadjuvant and Adjuvant Translational Science Program, senior member, Moffitt Cancer Center, Research Institute Departments of Cutaneous Oncology and Immunology; professor, Oncologic Sciences, University of South Florida Morsani College of Medicine; chair, Scientific Committee, Oncology Research Information Exchange Network (ORIEN); chair, ORIEN ImmunoOncology Research Subcommittee, discusses the use of high-dose bolus interleukin-2 (IL-2) with concurrent low-dose ipilimumab (Yervoy), followed sequentially by nivolumab (Opdivo), in patients with advanced melanoma.

These patients had experienced disease progression despite receiving immunotherapy, specifically anti-PD-1-based treatments either alone or in combination, as well as BRAF and MEK inhibitors if their tumors had BRAF mutations, Tarhini begins. The treatment protocol involved up to 3 courses of combination therapy, each lasting 12 weeks and divided into 4 cycles, with each cycle spanning 3 weeks.

The regimen began with a low dose of ipilimumab administered concurrently with high-dose IL-2 during the first week of the first 2 cycles, he explains. Starting in the first week of the third cycle, nivolumab, an anti–PD-1 therapy, was introduced. Disease assessments were conducted at the 12-week mark, and patients who demonstrated stable disease or a positive response were eligible for further treatment courses, Tarhini states.

This regimen was relatively well tolerated and yielded promising clinical activity, though the data are still preliminary, he continues. Among the 13 patients who reached the first response assessment, 2 achieved complete responses. These responses have proven durable, with 1 patient remaining in remission for over 37.7 months and the other for more than 14.1 months, Tarhini reports. This finding is particularly significant in a field where alternative treatment options are scarce, according to Tarhini. The study is ongoing, and as a next step, Tarhini states that investigators are conducting biomarker analyses and mechanistic studies to understand why some patients benefit from this regimen but others do not. This research will help refine eligibility criteria to better enroll patientswho are most likely to respond to this treatment, Tarhini concludes.