An internationally recognized melanoma researcher at Moffitt Cancer Center and colleagues at the University of Kiel in Germany, including Axel Hauschild, M.D., and Katharina C. Kδhler, M.D., have published an article in the July 20 issue of the Journal of Clinical Oncology that describes immune-related adverse events for patients receiving either tremelimumab or ipilimumab.
Both drugs are anti-CTLA-antibodies with similar mechanisms of action but manufactured by different companies. Ipilimumab is an immunoglobulin G1 with a plasma half-life of 12 to 14 days. Tremelimumab is an immunoglobulin G2 with a plasma half-life of 22 days. Both have been extensively tested in metastatic melanoma, and ipilimumab was approved in 2011 by the U.S. Food and Drug Administration for treating metastatic melanoma and other cancers.
"During treatment with ipilimumab and tremelimumab, a unique set of adverse events may occur called 'immune-related adverse events,' or irAEs," said study lead author Jeffrey S. Weber, M.D., Ph.D., director of Moffitt's Donald A. Adam Comprehensive Melanoma Research Center of Excellence. "These irAEs may include colitis, hepatitis, pancreatitis, lymphadenopathy, neuropathies and nephritis."
According to Weber, appropriate management of these side effects requires the cooperation of a multidisciplinary physician-led team that includes nurse practitioners and infusion nurses. He recommends that specialists, including gastroenterologists, endocrinologists, hepatologists, dermatologists and surgeons, receive education on managing these symptoms. Early recognition of irAEs and initiation of treatment are crucial, the researchers said.
In their review of studies on the drugs' adverse effects, the researchers also found that irAEs correlated with treatment response in some studies. The reduction in tumor burden came in four patterns after week 12 of treatment.
"Anti-CTLA-4 antibodies have shown patterns of anti-tumor response that are different from responses to conventional chemotherapy," explained Weber. "Because responses can occur slowly or be mixed, 12 weeks has been the time to first evaluation with ipilimumab."
Weber and his colleagues also reviewed the new set of response criteria that have been created -- immune related response criteria, or irRC -- to evaluate disease progression and benefit with immune checkpoint inhibitors such as ipilimumab. The irRC criteria have been compared with modified World Health Organization criteria in studies of patients receiving ipilimumab and can provide valuable information to oncologists as to when to stop or continue treatment with ipilimumab.
"In this study, we provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them along with the unusual kinetics of response associated with ipilimumab therapy," Weber said.
- J. S. Weber, K. C. Kahler, A. Hauschild. Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab. Journal of Clinical Oncology, 2012; 30 (21): 2691 DOI: 10.1200/JCO.2012.41.6750
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