When Carl Harrington was diagnosed with Waldenstrom macroglobulinemia (WM) in 2006, he did not need immediate treatment, which was fortunate, because the rare disease had no approved therapies at the time. Instead, a watchful waiting strategy was proposed—his medical team monitored his health while he carried on with his daily life, hoping that research would catch up to his disease.
Now president of the International Waldenstrom’s Macroglobulinemia Foundation (www.iwmf.com
), Harrington was able to announce to his fellow patients in late January that the first drug for the disease was approved, partly due to the organization’s funding of WM research.
A rare and indolent non-Hodgkin lymphoma, WM originates from a type of white blood cell that develops in the bone marrow, called B cells. These cells produce high levels of immunoglobulin M protein, which can crowd out other important cells. While the cancer is considered slow-growing, the median survival is five to 11 years, and there is no cure.
Before Jan. 29, 2015, there were also no treatments approved specifically for the disease. Through a concerted effort by a pair of pharmaceutical companies, working with the Food and Drug Administration and its breakthrough status program, Imbruvica (ibrutinib) was granted approval for WM. The announcement was made two months ahead of the expected FDA review date.
The FDA made its decision based on a small phase 2 study that showed that 62 percent of patients who received daily Imbruvica had a response, with 51 percent achieving a partial response and 11 percent having a very good partial response. Side effects included neutropenia, thrombocytopenia, diarrhea, rash and nausea.
"As president of the International Waldenstrom’s Macroglobulinemia Foundation (IWMF), I am thrilled by the FDA approval of Imbruvica. For the first time, WM patients have a treatment specifically studied and approved to treat our orphan disease,” Harrington says. “What’s interesting about this approval is that it’s not just for refractory or relapsed, it’s for everybody.”
WM Sees Success in Precision Medicine
Precision, or personalized, medicine has certainly opened the door for research into the rare disease, which affects about 1,500 new patients each year in the U.S. Work being done at Dana-Farber Cancer Institute’s Bing Center for Waldenstrom's Macroglobulinemia helped Imbruvica gain approval for treatment of the disease.
Steven P. Treon, lead investigator of the Imbruvica trial and director of the Bing Center, and his colleagues pioneered the work that revealed the genetic components of WM. A majority of patients have a genetic mutation, called MYD88, which has been shown to be susceptible to Imbruvica.
“Imbruvica seems to be very effective in people with that MYD88 aberration, which is about 90 percent of us,” Harrington says. About thirty percent of patients also have a mutation called CXCR4. This mutation appears to have resistance to Imbruvica, but researchers are now looking at ways to circumvent it.
“We can’t fund all the research we’d like, but we can fund portions of the research, including that which led to the discovery of MYD88 and other things that are proving critical to our disease,” he says, adding that to date, the IWMF has funded more than $7.5 million worth of research into WM.
Harrington, who has continued with his watchful waiting strategy, says it helps to have an approved treatment in his back pocket. And while Imbruvica’s approval is a success for the advocacy group, it is really only the beginning, he says.
One field Harrington says the foundation is closely watching is immunotherapy.
“Certainly a big piece of news out of ASH (American Society of Hematology) was about immunotherapy and training your T cells to do the dirty work for you,” he says. “We’re funding a project that does that for Waldenstrom’s.”
The momentum of research has never been greater in the 70 years since the rare disease was first identified. “There are a whole bunch of companies that are fortunately paying attention to our orphan disease, and we’ve never had as many clinical trials as we do now,” he says. “We’re grateful for that, and we’re encouraging our patients to participate in them.”
There are currently about 80 clinical trials ongoing for WM. "The IWMF’s vision is to support everyone affected by Waldenstrom’s macroglobulinemia while advancing the search for a cure,” Harrington says. “We won’t rest until we find a cure."