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Medline ® Abstracts for References 35,36

of 'Toxicities associated with checkpoint inhibitor immunotherapy'

35
 
 
https://www.fda.gov/downloads/Drugs/DrugSafety/PostMarketDrugsafetyInformationforPatientsandProviders/UCM249435
 
no abstract available
36
TI
Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma.
AU
Weber JS, Dummer R, de Pril V, LebbéC, Hodi FS, MDX010-20 Investigators
SO
Cancer. 2013 May;119(9):1675-82. Epub 2013 Feb 7.
 
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.
AD
Donald A. Adam Comprehensive Melanoma Research Center, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. jeffrey.weber@moffitt.org
PMID