Five things we learned about immunotherapy in 2016

A version of this article originally appeared on the Johns Hopkins Medicine blog, Cancer Matters.

Immunotherapy has become one of the most promising areas of cancer research, and the number of cancers successfully treated by immunotherapy is growing. There are now four FDA-approved immunotherapy drugs that target immune system checkpoints to treat six types of cancer.

Video: Bloomberg~Kimmel Institute for Cancer Immunotherapy

Drew Pardoll, director of the Johns Hopkins Bloomberg–Kimmel Institute for Cancer Immunotherapy, reviews the research findings that have made a significant impact on this field this year.

Pardoll's picks for the top five research findings are:

  • Virus-associated skin cancer responds to immunotherapy. Results of a study published in April gave oncologists the first indication that "a new category of cancer may be highly responsive to immunotherapy," says Pardoll. The study, led by the Fred Hutchinson Cancer Research Center and Johns Hopkins' Bloomberg–Kimmel Institute, showed that half of 25 patients with Merkel cell carcinoma, a rare, virus-linked skin cancer, had major tumor shrinkage and outperformed conventional chemotherapy. Pardoll says that worldwide, more than 20 percent of cancers are associated with viruses, and scientists are studying such cancers for their response to immunotherapy.

  • Immunotherapy replaces chemo as first-line weapon against lung cancer. The FDA approved two immunotherapy drugs as a second course of treatment for patients with lung cancer who do not respond to chemotherapy. Then, a Johns Hopkins study published in November showed that lung cancer patients taking the immunotherapy drug pembrolizumab as first-line therapy fared much better than those who took chemo. Pardoll says that the study was a "dramatic demonstration" that so-called PD-L1 proteins are a biomarker for response to the therapy. Results from this study led the FDA to approve pembrolizumab as the first treatment for patients with lung cancer whose tumors express PD-L1 proteins.

  • Safety trials of immunotherapy for early lung cancer pass "Go." In October, researchers from the Bloomberg–Kimmel Institute presented early data, collected from a small number of patients with lung cancer, which demonstrated that giving the immunotherapy drug nivolumab before their surgery to remove the cancer is safe and feasible. At the time of surgery, 40 percent of patients had over 90 percent regression of their tumor associated with influx of killer T cells. "Immunotherapy could potentially work inside the early-stage tumor as a vaccine that activates T cells, which can circulate through the body and attack residual deposits of cancer, ultimately causing relapse after surgery," says Pardoll.

  • When immunotherapy doesn't work, researchers ask why. Despite response rates of between 20 to 50 percent in certain groups of patients, scientists still don't know why the majority of people with cancer don't respond to immunotherapy drugs. Some of the first clues to immunotherapy resistance are beginning to unravel. This month, UCLA led a team of researchers, including those at the Bloomberg–Kimmel Institute, in publishing results in Cancer Discovery that point to genetic mutations in a small number of patients that cause the signaling system to fail to rouse the immune system's attack on cancer cells. Additional research is being conducted to see if more patients who are resistant to immunotherapy have these and other mutations that influence the immune system.

  • Oncologists need more education on how to spot immunotherapy side effects early. No drug is immune from side effects, and immunotherapy is no different. The New York Times recently highlighted some of the therapy's known side effects, including rare cases of diabetes, inflammatory arthritis, and even death. Oncologists like Kimmel Cancer Center's Julie Brahmer are sharing their knowledge of immunotherapy's side effects and how to combat them at medical meetings and educational seminars. In a panel discussion during The Washington Post's Chasing Cancer summit, Pardoll said that oncologists "need to go back to school" to learn about a different set of toxicities than what they are used to managing with chemotherapy. He adds that oncologists also need to educate patients receiving immunotherapy about symptoms that should prompt an immediate call to the doctor.

Looking forward, Pardoll says that emerging basic science research and clinical trials are demonstrating how to block multiple immune checkpoints simultaneously. Immunologists also are studying ways to develop therapies that target the metabolism of the immune system, thereby strengthening tumor-killing activity. The final frontier, he says, may be in gaining more understanding about how the microbiome or microorganisms, such as bacteria, influence tumors. Overall, he says, 2016 has been a good year for immunotherapy.

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