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What are immune checkpoint inhibitors?
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Immune checkpoint inhibitors are used to prevent immune cells from being turned off by cancer cells, which further allow T cells to stop a tumor from growing.
Although a tumor can be reduced in size within weeks with the use of conventional chemotherapy, immune checkpoint inhibitors may take several months to even begin to shrink the tumor.
The treatment process of immune checkpoint inhibitors can sometimes include swelling of the tumor, known as pseudopregression. The tumor swells from the significant number of activated T cells and other cell types and substances that enter the tumor. However, the increased size is followed by tumor shrinkage or complete eradication.
Approved checkpoint inhibitors
The focus of cancer drug development is moving more toward immunotherapeutics, which include immune checkpoint inhibitors. There are several immune checkpoint inhibitors that have been approved by the FDA for the treatment of melanoma, and many of these agents are undergoing testing for use in treatment of other cancers. These include ipilimumab (Yervoy; Bristol-Myers Squibb), nivolumab (Opdivo; Bristol-Myers Squibb) and pembrolizumab (Keytruda; Merck).
Some patients experience an autoimmune reaction to treatment with immune checkpoint inhibitors. An autoimmune reaction occurs in nearly 10% of cases, and it typically lasts 6 to 12 weeks after treatment is initiated. These adverse events include alterations in energy levels, diarrhea, eye irritation, jaundice, rash and trouble breathing. In order to decrease the immune response from the checkpoint inhibitor, physicians may prescribe a steroid and/or temporarily stop treatment.
Looking ahead
In addition to the currently marketed immune checkpoint inhibitors, a number of new drugs are in the advanced stages of development. These include tremelimumab, elotuzumab, RG7446 and avelumab. Ipilimumab is currently being mirrored by various other anti–PD-1 drugs that are under clinical development and are expected to emerge soon.
For more information:
www.cancer.gov/news-events/cancer-currents-blog/2015/pd1-trials
oncology.jamanetwork.com/article.aspx?articleid=2174768