August 29, 2012
1 min read

Interleukin-21 linked to favorable survival outcomes in metastatic melanoma

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Interleukin-21 yielded an overall response rate of more than 20% in a cohort of patients with metastatic melanoma, according to results of a phase 2 study.

The researchers conducted the multicenter study to evaluate interleukin-21 (IL-21) — a cytokine that has potent regulatory effects on immune system cells — with regard to efficacy, toxicity, PFS, immunogenicity and biomarker profile.

Eligible patients had no prior systemic therapy and limited-disease metastatic melanoma.

The researchers evaluated 40 patients. Study protocols called for three dosing regimens.

Three patients in cohort 1 were assigned to 50 mcg/kg per day by outpatient IV bolus injection for 5 days of each week during weeks 1, 3 and 5 of an 8-week cycle.

Thirty patients in cohort 2 received 30 mcg/kg per day on the same schedule.

Seven patients in cohort 3 received 50 mcg/kg per day for 5 days of each week during weeks 1 and 3 of a 6-week cycle.

Dose-limiting toxicities occurred in two patients in cohort 1 and four patients in cohort 3. Fatigue, rash, diarrhea, nausea and myalgia were the most commonly reported adverse events.

The researchers observed a 22.5% overall response rate, including nine confirmed partial responses (median response duration, 5.3 months). Sixteen patients achieved stable disease (median response duration, 5.3 months). Overall response rate did not appear to be dependent on IL-21 receptor expression or BRAF mutation status, the researchers said.

The researchers observed a median PFS of 4.3 months and a median OS of 12.4 months (95% CI, 10.09-17.81).

“The response rate seen in this study is higher than that seen with IL-2 and ipilimumab (Yervoy, Bristol-Myers Squibb),” the researchers wrote. “IL-21 is generally well tolerated and safely administered in an outpatient setting, an advantage over other immunotherapeutic agents, which makes it ideal for combination with other agents … There is also scientific rationale for combining IL-21 with tyrosine kinase inhibitors, as well as other immunotherapeutic agents that may augment the immune response and possibly increase durable responses. Future trials should continue to explore molecular correlates of response to allow for targeted selective treatment of patients with metastatic melanoma.”

Disclosure: The researchers report research funding from ZymoGenetics.