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

By Media Staff

on Thursday, May 15, 2014

Pictured: William Tap William Tap, Chief of the Sarcoma Medical Oncology Service

New Memorial Sloan Kettering research demonstrates the powerful clinical benefit of giving patients a drug that targets the molecular abnormality driving the growth of a rare and debilitating joint disease.

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.



As I understand it "Cartilage undergoes a normal cycle of breakdown and repair, but in the condition of osteoarthritis, the cartilage is not replaced effectively, and ultimately the joint lining wears thin." so do you think CSF1 can be used to treat osteoarthritis?


John, we consulted with Dr. Tap and he responded that he is "unaware of any preclinical data or rationale for PLX3397 use in osteoarthritis." Thanks for reaching out.

I wasn't thinking that PLX3397 could treat osteoarthritis. Since CSF1 is the reason for the linings overgrowth I thought it might treat osteoarthritis (which is a thinning of the lining) . . .


Not to Dr. Tap's knowledge, John.

I just was diagnosed with a recurrence of PVNS after 9 years. Originally it was localized, but now it is diffuse. I was wondering how to potentialyl qualify for the phase III trial.

Daniel, we reached out to Dr. Tap, and he says: "The Phase III trial is still some time away, but the Current trial is still open if interested. There are several sites across the country depending on where he lives. We would also be happy to see him in clinic." You can learn more about the current trial here:

That is wonderful news. I live in Minneapolis, but grew up in NY and my father is a physician in NYC and Westchester so the NY location is best for me. I am waiting to hear from the PVNS specialist at the University of MN and will discuss my intention to attend Dr. Tap's clinic. I will call Dr. Tap's offices within the next few days to set up an appointment. I am truly grateful for modern medicine and Dr. Tap's generous offer to see me.

Hi, I am a 44 years old Swede with diffuse PVNS. I got my hip replaced 2010 in a private clinic in Switzerland but then had to make a new replacement one year later, after loosing the stem and a lot of other complications. They told it was PVNS after the first operation but that "it was not there" by the second operation. However they missed the giant mass that had grown outside the hip in between the ilias and psoas muscle. This I found out half a year ago after having problems with bowels and strong sudden hip pain then and then. The size of the tumor is 18*7*8 cm and the biopsy test showed, as I understood it, that it was mostly blood, no malignancy. I wonder if I can take part in the tests of the new drug?

Hi, I am 37 years old and I from Brazil.
I am very interested in this new study on this drug would be able to do with our tumors stop growing and even recede, so to be able to lead a more normal life.
Is there any joint work with Brazil? How I could be part of this study? Next week I'm traveling to Vegas and going to Miami in December. Please do not hesitate to warn me as if there is the possibility of being part of a study group.
Thank you very much.

I'm too active. I played a lot of tennis, at this time I can not play tennis at the knee but do gymnastics and pilates and sometimes I ride. You think you have to stop exercising due to this problem SVNP? I have several tumors behind the right knee, one being 10 x 3cm.
I would be a big help to people who are studying this disease can guide me on how to continue my life without aggravating the disease, since little is known about this problem globally.
From already thank you very much for everything.

Hi, I have had pvns in my ankle joint for 13 years... My feeling is that it has regrown after a partial synevectomy 3 years ago. Are there any hospitals in Boston that are participating in the research and if so who? Thank you for your work! Much needed as this is a painful and debilitating condition.

Hi Dr. Tap. I am a patient of Dr. Wagner's at Dana Faber. I have extremely diffuse / radiation resistant PVNS. Gleevec has prevented me from amputation and more surgeries, however damage and pain continues in my left knee and distal quadricep. More importantly and very unfortunately because I have a another unrelated chronic illness, Gleevec tends to interact with some potential drug therapy options I very much need to try. I would like to be able to take medication that has less side effects on the liver like Gleevec.

Thus, my question is related to the potentially know drug interactions of PLX3397? I image your case studies, and future drug trials will be elevating such drug interactions... If you could provide me a list of the most statistically significant interactions, I would really appreciate it.

Thank you for your consideration.

Eric, we reached out to Dr. Tap and he is trying to get some information for you. We will follow up with you at the email address you provided when we hear back from him. Thank you for your comment.

I have an 18 yr old son with diffuse PVNS in his rt knee. He had front and back arthroscopic synovectomy in 2011. PVNS has now returned to the back of his knee. Options are MCS110 Novartis trial, repeat arthroscopic surgery or open back surgery. I just came across this post on PLX3397. How does this work and how is that different from MCS110

Adrienne, we're sorry to hear about your son's condition. We sent your questions to Dr. Tap, but he said he is unable to answer them without seeing your son and reviewing his records. If you'd like to make an appointment, you can call 800-525-2225 or go to for more information. Thank you for your comment.

Hi sorry for the confusion in my comment. My question is how does PLX3397 work and what is the difference between PLX3397 and MSC110. I believe PLX3397 is a chemotherapy drug. Not sure about MSC110. To the best oft knowledge both are currently in phase II of testing. Both have shown reduction in tumor size but in both tumors have returned when the drug is stopped. I would like to get more information on the drug before we ever consider either of these as an option. Thank you

Adrienne, MSK doesn't have any trials with MSC110 so we don't have any information that we can provide on our website or blog. We recommend that you speak with your son's treating physician about it, or contact the drug's manufacturer. Thanks for your comment.

I did not see this question area & so had tried to emailDr. Tap, but they were returned to me. My 17 year old daugter has had 2 hip synovectomies ( same hip) over the las 2 years for PNVS. She is still having continuous pain & lack of mobility. THey are now saying she has arthritis in that joint. Nothing helps. We would be most interested in being in a trial for any new treatment. Prior to all this she was extremely active, playing volleyball, soccer and mostly was a competitive figure skater. Now she is unable to do any sports and it has greatly impacted her life. Any trials or physicians you recommend in the St. Louis MO area ? thanks !

Sheila, we recommend you check to see if there are any trials for PVNS at hospitals in your area. Thank you for your comment.

Are there any sites available in Florida? I'd be interested to participate in this study as I have had 2 arthroscopic synovectomy surgeries in 2008 and 2013 both times in my left shoulder. My doctor informed me that if the PVNS returned again, then I would probably have to go to an Oncologist for further treatment.

Zachary, we recommend that you go to, a database of clinical trials maintained by the National Institutes of Health, to look for open studies on PVNS in your area of the country. Thank you for your comment.

I was diagnosed with diffuse PVNS in my right knee in 2009 and underwent a complete synovectomy. Slowly, my symptoms have slowly started to return. I recently underwent an MRI but have been unable to find a physician familiar with the condition in my area. Last time, the pain became absolutely unbearable and debilitating as the disease progressed. I want to explore treatment options before it reaches that point again. I will be visiting the NY area within the next few weeks. Is it possible to see Dr. Tap for a consultation? Additionally, I will be moving to NYC in May and would like to try to be part of the next phase of clinical trials. Thanks!

Dear Miller, we are sorry to hear about your diagnosis. To make an appointment, please call our Physician Referral Service at 800-525-2225. The knowledgeable staff there can also answer your questions about our clinical trials. There is at least one trial open at MSK for people with PVNS:
Thank you for reaching out to us.

I had for years of intermittent hip and groin pain. I'm 37, 6'2", 190lbs. I have always been lean and in good shape. I first noticed the pain doing a yoga stretch but it went away, months later I felt like I has pulled a groin muscle or adductor muscle. I was going to a chiropractor and taking 2-3 Norco a day to deal with the pain. Being a professional classical guitarist I figured it was from my long rehearsal sessions and active lifestyle surfing, yoga, Pilates, hiking, bicycle riding, running. After a few years I developed a noticeable limp. I finally went to a real doctor and my X-rays showed advanced arthritis, cysts, and joint space narrowing. I was told to have a shot of cortisone but avoided it. I went for a second, third, and after about 8 consultations was finally told I might have PVNS of the hip. I was sent from Kaiser's Dr. Sheth in Irvine to the expert Dr. Christopher Helmstedter at Kaiser in Baldwin Park, Ca. He said it was the most difficult case he has ever seen. It took him and Dr. Michael Li Chen 6+ hours to clean out the PVNS and install my Johnson and Johnson 54mm highly crossed polyethylene pinnacle cup, and liner, 32mm ceramic ball, and summit titanium stem. I'm 8 weeks post operation and doing great. I hope to be surfing again in a few months. So far I've resumed hiking and will resume weight training soon. I hope we find a cure or a way to identify this PVNS disease faster. I could have maybe saved my real hip if I hadn't been misdiagnosed for 4 years. Thank god for wonderful, passionate doctors like Helmstedter, Chen, and Sheth!

I was diagnosed with severe diffuse PVS in the knee over 30 yrs ago at 24... Boy was it aggressive... 13 synovectomies in all... After 6 total open knee ops with recurrance it was decided that we go arthroscopically and 7 of those followed... Many blood filled aspirations in between... After 15 years of that, a knee replacement was needed and then a minor revision about 2 years after that... 15 ops in about 17 years 1984-2001... The replacement helped and I haven't needed surgery in 14yrs now... The patella tendon and kneecap were not replaced ??? I wish they had been... Cement was put behind the kneecap to protect it... That only worked for so long... The cement has since chafed and the kneecap is now rubbing and wearing away... There has been and increase in pain of late and the joint is again warm to the touch... Kinda scared that its back growing around the patella but I dont know for sure... I have an appointment with a top notch surgeon who specializes in revisions... Its been 14 years since my replacement... In 1984 much wasn't known about this disease... You tried to clean it out the best you could and hoped for the best... Now we have these wonderful doctors and social media to get the word out about the latest treatments and possible cures... Hats off to these doctors... If you are diagnosed with a severe case of this dreaded disease please seek out a surgeon that has experience with it... And certainly spend time educating youself online with places such as this... I say try the treatments available that have the best success rate ... If 2 total open synovectomies didn't stop it, 2 more wont either... Try a successful treatment... Wishing you all the best... Eric Weed...

Hello, greetings from Cincinnati, Ohio
I have PVNS in both knees. Multiple surgeries on the right and one on the left.
Before I go with amputation, I would like to try the clinical trial drugs. I know of PLX3397, MCS110& NCT01207492. I am so confused on how to get started. I AM willing to travel. Can you help by pointing me in the right direction?

Kristen, if you would like to come to MSK for treatment or a second opinion, you can call our Physician Referral Service at 800-525-2225 or go to for more information. We sent your question to Dr. Tap, and he said that because PVNS in both knees is unusual, the trial here might be a good option for you.

If you are interested in treatment closer to home, you might also want to go to to search for other PVNS trials in your area. Thank you for your comment.

13 y/o daughter had surgery on right knee in Dec 2012 for pvns - saw dr today less than three years later with more swelling & crunching/grinding starting up again- she had to give up basketball, track and was in wheelchair through most of 5th grade - now starting 8th grade may have to change schools due to pvns recurring in knee - Is there ANY clinical trial for patients under age 18 anywhere?
We are in Baton Rouge, La.
So very appreciative of you doctors who do the research!

Anna, we sent your query to Dr. Tap, and unfortunately he is not aware of any PVNS trials for people under age 18. We recommend you check, which is maintained by the National Institutes of Health and includes trials all over the world. Best wishes to you and your daughter.

I have diffuse PVNS in my right ankle, i had two open synovectomy but the tumor always regrowth and doctors tell me it is impossible to totally cut all the tumor from my foot, i am Colombian but i would like to know if there is any chance to be in the trial. Pain and stiffness is high. Amputation is one of the solutions.

Johan, if you would like to come to the US for treatment at MSK, you can contact our International Center at or go to for more information.

You may also want to look at to find out if there is a clinical trial closer to your home. This is a database maintained by the US National Institutes of Health that includes clinical trials around the world for a number of different conditions.

Best wishes to you and thank you for your comment.


I am a 25 year old male with diffuse PVNS in my right hip. I started feeling pain/loss range of movement/crunching at the age of 15. I was misdiagnosed until the age of 19. I had 2 arthoscopic synovectomy surgeries in 2010 and in 2011 as it came back rapidly. Since then my hip has been 'Okay', up until a few months ago. Now it is starting to get 'stuck' and painful again on a daily basis. I would love to be a part of any research and a part of these trials.

Alex, if you're interested in participating in this trial at MSK, you can call 800-525-2225 or go to for more information on making an appointment. If you're not able to come to New York for treatment, we recommend you go to to find other places that have open trials for PVNS. Thank you for your comment.

My 22 year old son has PVNS in the right knee (back and forth) from last year. Doctors have advised to wait for the completion of the trial, advising against surgery for the moment. Now he is taking the medication ARCOXIA 60 mg every 15 days for the inflammation and ice bag once a day (the swelling subsides for the duration of treatment). Disability is psychologically hard for a young man. Can you give us some advice? Is there some other medication to reduce inflammation? Greetings from Italy, Santa Maria Capua Vetere

Gennaro, we sent your comment to Dr. Tap, and he recommended that you contact Dr. Silvia Stacchiotti at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan. Best wishes to your son, and thank you for your comment.

I have PVNS in my right ankle. I had two surgery done. but it keep coming back. I have pain in my ankle. I am interested in participating in the trial for PLX3397. thank you.

I was diagnosed with PVNS back in december and have had 2 orthroscopic knee surgeries already. was just told that it grew back for a 3rd time and have been trying to find alternative methods before having to get surgery again. was reading that it comes back 45% of the time after surgery, so if there is another way (such as PLX3397), i would be very interested. I work in NYC, so not to far from MSK, so how can i get involved with this test? i've previously gone to NYULMC for all of my PVNS issues. ty

Hi, I´m a 43 year male from England UK.

I was diagnosed with P.V.N.S about 3 years ago after 3 wrong diagnosis.

Since then I have a complete synovectomy of the knee lining, but within 18 months the condition returned and is worse than it was before.

To make matters worse, I have a large tumor at the back of my knee which surgically risky to remove (1 in 10 chance of paralysis) and have been told because it´s enlarging they would like me to have it removed, as the risk of doing nothing may be greater (total joint destruction or even worse chronic pain than I experience at present).

I found your article very interesting and it´s given myself and do doubt other unfortunate P.V.N.S sufferers some hope of a possible treatment for this dreadful disease.

If you are looking for volunteers to test your drug, I´d be more than happy to volunteer as at this point, I have very little to lose!


Paul Rogers

P.S. I started my own P.V.N.S patient support group to research further, and we dispelled some of the long held notions from past research in 1970s in UK that the disease only affects people in their 30´s and older. We have some sufferers on our group as young as 18. One common factor/pattern too is that most sufferers were highly physically active and suffered joint trauma, but continued intensive physical activity regardless. This may suggest some kind malfunctioning immune response that affected the cell genes? Just a wild theory, but it does seem odd how many have this pattern of intensive exercise, trauma, and then the disease onset.

My 19 yo daughter was diagnosed w PVNS of the left knee at age 14. Since then she has undergone two surgeries. On her third recurrence the swelling was compressing an artery and surgery was not recommended. Instead she was prescribed Gleevec. This seemed to minimize the tumor over time and keep it at bay, but not w/o causing terrible side affects associated w chemotherapy. She stopped taking the drug after 1 year, in December, 2014. For there first 6 months after stopping, regrowth was minimal. However, since June size and pain seems to be increasing. She returns to the oncologist in December. Wondering what the status is of the trial and if there are options other than additional surgery or chemotherapy.
Although not a life threatening disease, it is physically and psychologically hard on her. She is a college student who is looking for a way to rid or minimize the disease w/o the possibility of suffering life long side affects. Thank you for your time.

OUr 25 son was just diagnosed, the assumed culprit was a traumatic football injury five years ago. He had complained about tightness and calf pain for years. Finally the dr ordered an MRI. The tumor is on the back of his knee but all of his discomfort is in his calf. Is this normal?

In May, 2013 my than 9 year old daughter was diagnosed with diffuse PVNS in her left knee. In June 2013 she had synovectomy. We live in Chicago. I did not seek second opinion., but her let knee seems to be somewhat at a constant state of swelling, at times she complains of pain in her knee. Sometimes she complains about pains in different sites. My heart dies every time she reports any discomfort. I cut down ALL her sports, she is slowly starting swimming.
How this trail addresses children.
What do I need to do, I do not have any help. I raise her by myself.
Please respond,
Thank you.
Teresa Moskalewicz

Teresa, we're sorry to hear that your daughter is going through this. Dr. Tap said he is not aware of any clinical trials that include pediatric patients, but he has treated some younger patients with PVNS. If you'd like to make an appointment for a consultation with him, you can call 800-525-2225 or go to for more information. If you prefer to stay in Chicago, we recommend that you go to and find out who in your area is doing research on this disease. Thank you for your comment, and best wishes to you and your daughter.

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