Journal
CANCER
Volume 119, Issue 9, Pages 1675-1682Publisher
WILEY
DOI: 10.1002/cncr.27969
Keywords
adverse drug events; immune system phenomenon; ipilimumab; mechanism of action; metastatic melanoma
Categories
Funding
- AstraZeneca
- Novartis
- Cephalon
- Merck
- Transgene
- Bristol-Myers Squibb [NCT00094653]
- Roche
- GlaxoSmithKline
- Bayer
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BACKGROUND: Ipilimumab 3 mg/kg was the first agent to demonstrate improved survival in previously treated patients with metastatic melanoma in a phase 3 trial (MDX010-20). Ipilimumab produced a characteristic spectrum of immune-related adverse events (irAEs) of special interest, consistent with its immune-based mechanism of action. METHODS: In MDX010-20, 676 previously treated patients were randomized 3:1:1 to receive ipilimumab 3 mg/kg plus the glycoprotein 100 melanoma antigen vaccine (gp100), ipilimumab 3 mg/kg + placebo, or gp100 vaccine + placebo. For the current report, the authors conducted a detailed analysis of the time to onset and resolution of irAEs associated with ipilimumab therapy. RESULTS: Grade 2 through 5 irAEs generally developed during the induction phase of treatment (0-12 weeks). Most, including grade 3/4 irAEs, were reversible when managed with treatment guidelines using vigilant monitoring and corticosteroids. The median time to resolution (to grade 1 or 0 or to the grade at baseline) of irAEs that had an onset during the induction phase was approximately 6 weeks for grade 2 through 4 irAEs and 8 weeks for grade 3 and 4 irAEs. Across the entire study duration, most grade 2 through 4 irAEs resolved within 12 weeks. CONCLUSIONS: Most ipilimumab-associated irAEs, including grade 3/4 symptoms, developed within 12 weeks of initial dosing and resolved within 12 weeks of onset. IrAEs were well characterized in their evolution and could be managed using published algorithms. Cancer 2013; 119: 1675-82. (C) 2013 American Cancer Society.
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