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Soo Park, MD
Soo Park, MD
Posted: Friday, August 2, 2024
Although immune checkpoint inhibitor combinations have improved survival outcomes in melanoma, up to 60% of patients treated with nivolumab plus ipilimumab experience severe immune-related adverse events that often lead to discontinuation of therapy. Bilal Anouti, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues reportedly conducted the first study evaluating the front-line use of the interleukin-6 (IL-6) inhibitor tocilizumab to enhance the efficacy of these immune checkpoint inhibitors while reducing adverse events. The results of this trial were presented during the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 9553).
This phase II trial enrolled 35 patients with advanced melanoma to receive tocilizumab combined with 1 mg/kg of nivolumab plus 3 mg/kg of ipilimumab every 3 weeks for 12 weeks in the front-line setting. Tocilizumab was administered subcutaneously at 162 mg biweekly for six doses; 10 patients received 6 weeks of weekly tocilizumab followed by 6 weeks biweekly (dose dense).
The median follow-up was 18 months among patients on biweekly tocilizumab. By week 12, 44% of patients developed grade 3 or 4 immune-related adverse events, leading to 20% being hospitalized. The median time to onset of grade 3 or 4 immune-related adverse events was 7.4 weeks; 16% of patients discontinued treatment because of adverse events. The objective response and disease control rates at 12 weeks were 56% and 80%, respectively.
Patients who developed grade 3 or 4 immune-related adverse events demonstrated a trend toward higher IL-17 pathway gene expression, suggesting insufficient inhibition of the IL-6/T-helper 17 pathway. Therefore, 10 patients received the dose-dense regimen to better inhibit this pathway. The median follow-up in the dose-dense group was 7 months. By week 12, 40% of patients developed grade 3 or 4 immune-related adverse events, leading to 30% being hospitalized; these events led to treatment discontinuation in 30% of participants. The objective response and disease control rates at 12 weeks were 70% and 80%, respectively.
Disclosure: Dr. Anouti reported no conflicts of interest. For full disclosures of the other study authors, visit coi.asco.org.
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