Stanford Cancer Institute News

Fall 2017

David Miklos, MD, PhD, Associate Professor in the Department of Medicine-BMT, SCI member

Drug Discovery

First FDA-Approved Treatment for Chronic Graft Versus Host Disease

The work of Stanford researchers has led to the first-ever approval from the Food and Drug Administration (FDA) for a drug to treat graft versus host disease (GVHD)—a potentially serious complication of hematopoietic cell transplants that utilize cells from a donor not related to the transplant recipient. Hematopoietic cell and bone marrow transplants (collectively referred to as HCT transplants) are used to treat some blood and bone marrow and other select cancers. Until now, doctors relied on corticosteroids to treat GVHD, but the long-term use of steroids causes many side effects, and GVHD frequently re- emerges when steroids are stopped.

“We’ve been looking for a long time for targeted effective therapies to get patients with chronic GVHD off steroids,” said David Miklos, MD, PhD, Associate Professor in the Department of Medicine-Blood & Marrow Transplantation (BMT), and an SCI member. “But other drugs, even those that showed early promise, have all ended up failing to show benefit in randomized clinical trials.”

GVHD is caused when immune cells from an unrelated donor start attacking the normal tissues of an HCT recipient. This can lead to painful, debilitating problems in organs from the skin and mouth to the liver and lungs, including itchy rashes, nausea and vomiting, muscle weakness, and breathing difficulty.

Miklos discovered that B lymphocytes—one type of immune cell—are critical to the development of chronic GVHD. Blocking B cell activity, he hypothesized, could prevent or treat the disease. Ibrutinib—a drug first developed to treat B cell cancers and already approved for multiple cancer types—was able to potently deplete B cells from an HCT donor. Miklos approached Pharmacyclics, the Sunnyvale-based company that makes ibrutinib, about launching a clinical trial of the drug for GVHD; the company agreed.

Last year, Miklos and his colleagues presented the results of that trial at the annual meeting of the American Society of Hematology. Sixty-seven percent of patients had improvements in their GVHD after taking ibrutinib; in 48 percent of patients, improvements lasted at least five months. The research was published in the September 2017 issue of the journal, Blood.

On the heels of the findings, the FDA granted a breakthrough designation to the drug, meaning it could move quickly through the approval process. In August, the FDA approved ibrutinib for the treatment of patients with chronic GVHD that has failed at least one systemic treatment.

Now, Miklos and his colleagues are working on a trial to see if ibrutinib is effective in patients with earlier stages of GVHD.