Study Suggests Targeted Drug Is a Potential Therapy for Rare Joint Disorder PVNS

Pictured: William Tap

William Tap, Chief of the Sarcoma Medical Oncology Service

This is the first in a series of posts about new research Memorial Sloan Kettering investigators are presenting at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) — one of the largest educational and scientific events in the international oncology community — which will take place from May 30 through June 3 in Chicago.

New research from Memorial Sloan Kettering investigators is shedding light on a potential therapy for pigmented villonodular synovitis (PVNS), a rare and destructive joint disorder that affects approximately 600 young and middle-aged adults in the United States each year.

Patients with PVNS experience an inflammation and overgrowth of the synovium, or joint lining, which results in swelling, pain, and reduced mobility in the affected joint. The knee is the most common site involved, followed by the hip. Advanced cases of PVNS can be extremely debilitating.

Now a study led by medical oncologist William Tap, Chief of the Sarcoma Medical Oncology Service, suggests that a drug blocking a protein known to promote PVNS could alleviate these symptoms and improve quality of life.

A Tumor, But Not a Cancer

While the overgrowth of the joint lining may be referred to as a tumor, PVNS is not considered a cancer because the growth usually remains within a single joint and is not known to cause death.

Such tumors are removed surgically, and some patients receive radiation as well. In some cases the disease may recur after treatment, requiring additional surgery or a joint replacement. Eventually, PVNS may advance to the point that it is no longer operable, and the tumor will begin to further invade the joint, wrapping around bones, tendons, and ligaments.

There are no drugs approved to treat PVNS once it has progressed, and patients with advanced forms of the disease have few treatment options, among them amputation.

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A Single Genetic Driver

Research has shown that a protein called colony stimulating factor 1 (CSF1) kinase is a driving force in the development and growth of advanced PVNS.

PVNS tumors express high levels of CSF1 because the tumor cells carry a specific genetic abnormality. This attracts an abundance of white blood cells called macrophages that overexpress a receptor for CSF1 . The influx of macrophages causes the inflammation and overgrowth of the joint lining, which can destroy the joint over time.

Armed with this knowledge, Memorial Sloan Kettering researchers organized a phase I clinical trial to test whether a novel drug called PLX3397, a tyrosine kinase inhibitor that potently inhibits the CSF1 receptor kinase, could safely slow the growth of PVNS.

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The Right Drug for the Right Molecular Abnormality

Among 14 patients with advanced PVNS, 11 responded to the drug, while three others had stable disease. The average reduction in tumor size among the 14 patients was 61 percent, and all experienced rapid, marked improvements in symptoms. Side effects from the drug were minimal.

“By taking this drug that potently inhibits a single genetic process, several patients with advanced PVNS appeared to experience, in a relatively short amount of time, relief from pain and stiffness as well as marked improvement in joint function, all with minimal side effects,” says Dr. Tap, who led the trial and will present the findings at the ASCO meeting on Sunday, June 1.

“This study demonstrates the powerful clinical benefit of matching the right drug to the right molecular abnormality, and further spurs excitement over the potential of precision medicine,” he adds.

The drug is moving to an international phase III clinical trial, which Dr. Tap is helping to organize.

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This research was supported by Plexxikon.


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I have just been diagnosed with diffuse PVNS in my right knee. Is there a report how the clinical trials went? And is there an international program by now? I live in London UK

Dear Anna, we’re sorry to hear about your diagnosis. We recommend you go to to find out whether this drug is available in any clinical trials in the UK. You may also want to contact the company that makes the drug, Daiichi-Sankyo. Thank you for your comment and best wishes to you.

I have been diagnosed with PVNS in my right ankle. I am looking for a doctor in Boston, MA or Florida. Can you recommend anyone?

Happy after getting this stuff