Interleukin-21 has activity in patients with metastatic melanoma: a phase II study.
OBJECTIVE
We report a multicenter phase II study of patients with metastatic melanoma (MM), evaluating the efficacy, toxicity, progression-free survival (PFS), immunogenicity, and biomarker profile of interleukin-21 (IL-21).


METHODS
Patients with no prior systemic therapy and with limited-disease MM were treated with IL-21 by using three different dosing regimens. Cohort 1 received 50 μg/kg per day by outpatient intravenous bolus injection for 5 days of each week during weeks 1, 3, and 5 of an 8-week cycle. Cohort 2 received 30 μg/kg per day on the same schedule, and cohort 3 received 50 μg/kg per day for 5 days of each week during weeks 1 and 3 of a 6-week cycle.


RESULTS
Forty patients were enrolled: three in cohort 1, 30 in cohort 2, and seven in cohort 3. Two patients in cohort 1 and four in cohort 3 had dose-limiting toxicities; all other patients were treated with a dose of 30 μg/kg per day. Common adverse events were fatigue, rash, diarrhea, nausea, and myalgia. Overall response rate (ORR) was 22.5%, with nine confirmed partial responses (median response duration, 5.3 months); 16 had stable disease (median response duration, 5.3 months). ORR did not appear to depended on IL-21 receptor expression or BRAF mutation status. The median PFS was 4.3 months and median overall survival (OS) was 12.4 months (95% CI, 10.09 to 17.81 months).


CONCLUSIONS
The ORR to IL-21 is 22.5% for first-line MM and warrants further investigation. The favorable PFS and OS suggest that this is an active agent in comparison to both historical NCIC Clinical Trials Group data and data from meta-analysis of Cooperative Group phase II trials.
Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada M4N 3M5. teresa.petrella@sunnybrook.ca
Teresa M
TM
Petrella
Richard
R
Tozer
Karl
K
Belanger
Kerry J
KJ
Savage
Ralph
R
Wong
Michael
M
Smylie
Suzanne
S
Kamel-Reid
Victor
V
Tron
Bingshu E
BE
Chen
Naomi N
NN
Hunder
Linda
L
Hagerman
Wendy
W
Walsh
Elizabeth A
EA
Eisenhauer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054316:Biomarkers, Pharmacological; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007378:Interleukins / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D015999:Multivariate Analysis; D012878:Skin Neoplasms / Q000628:therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D000098546:Interleukin-21
D054316:Biomarkers, Pharmacological; D053645:Interleukin-2 Receptor alpha Subunit; D007378:Interleukins; D000098546:Interleukin-21