
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.
Back to topA 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.
Back to topThe 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.
Back to topComments
Lisa BroadawaY
Dec 14, 2015 • 7:30 PM
Memorial Sloan Kettering
Dec 15, 2015 • 9:32 AM
In reply to Are there any clinical… by Lisa BroadawaY
Lisa, to find clinical trials in Atlanta, we recommend you go to www.clinicaltrials.gov, a database of trials maintained by the National Institutes of Health. Thank you for your comment.
Karla Richards
Jan 4, 2016 • 8:42 AM
First diagnosed in 2007, I have had two sinovectimies on my left knee. I had low dose radiation after the second surgery in 2009 as the PVNS returned within six months after the first surgery. All my procedures have been through the University of Michigan Cancer Center. This is the first I have read about trials for any new drug to alleviate swelling and pain and have just given into eventually getting joint replacement. I will contact my surgeon in Michigan as I know live in Minnesota about her knowledge of any trials available unless you have other suggestions. It is something we live with and are thankful it's not cancer but it would be wonderful to be more active. Thank you so much for the use of the site!
Barbara Lester
Jan 14, 2016 • 2:06 PM
New to PVNS, even though my knee hurt on and off for years, I never went in until I could not walk one morning, I had an on target diagnosis and the tumors were removed by my orthopedic surgeon.
He suggests exploring radiation therapy.
I live 2 hours out of NYC and feel I should get Dr Taps opinion.
I am interested in the clinical trial if I fit the profile and its not too late.
Memorial Sloan Kettering
Jan 14, 2016 • 5:24 PM
In reply to New to PVNS, even though my… by barbara lester
Barbara, thank you for your comment. The trial has advanced to phase III, and is currently open. You can learn more about it here: https://www.mskcc.org/cancer-care/clinical-trials/15-074
If you’d like to make an appointment with Dr. Tap, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment.
Lizz Martin
Mar 6, 2016 • 6:21 AM
Hello,
My 28 yr old daughter was diagnosed at 22 with PVNS in her knee. We live in Sydney Australia. So far she had had 2 lots of surgery. Her doctor is at RPA Sydney. He said she should not do drug trial as she is of child bearing age. We are keen to hell her and get this disease sorted out . I don't want her to have this life long and have read online about amputation etc . Can you direct us to drug trials or any treatment for her please ? Thank you in advance . Regards, Lizz for Jess
Hi Lizz, we’re sorry to hear your daughter is going through this. We recommend you go to www.clinicaltrials.gov, which is a database that contains information about clinical trials around the world. That way you’ll be able to find out if there is a clinical trial near you that may be appropriate. Thank you for your comment.
Vinay
May 6, 2016 • 3:02 PM
Hello,
I have been dealing with PVNS in my right knee in 2014. Had three arthroscopic complete synovectomies since then and the knee looks better about a month after surgery but the symptoms come back and the disease progresses rapidly. Most recent surgery, 3rd one was in March 2016 and my surgeon was surprised at the way the disease progressed all around the knee and suggested pursuing other options which may help slow the rapid progression of this disease. Are your clinical trials still open?
Thank you.
Vinay, this trial is still open. If you’re interested in participating at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. If you’re not in the NYC area, you can go to https://clinicaltrials.gov/ct2/show/study/NCT02371369?term=PLX3397&show… for a list of all the centers that are participating in the trial. Thank you for your comment.
Angela Snell
Jun 24, 2016 • 8:38 AM
Memorial Sloan Kettering
Jun 24, 2016 • 12:04 PM
In reply to Hi I'm from Yorkshire and… by Angela Snell
Dear Angela, we are sorry to hear about your diagnosis. Your fears are certainly common and understandable. We recommend that you discuss your concerns with your oncologist, and reach out to a social worker or support group to get the support and encouragement you need to help you cope during this difficult time. We wish you well as you move forward with treatment.
Blair
Jun 26, 2016 • 10:20 PM
Hello! First, I want to say that I admire the work you are doing and am grateful for doctors like you! Second, I was wondering if there is a list to put your name on for any upcoming trials? I have pvns in one, possibly both, knees. The left knee started when I was 17 and I had two surgeries to remove tissue that same year. Now, my other knee has been exhibiting the same symptoms.
Thank you!
Blair, if you’re interested in participating in the trial for PVNS at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. If you’re not able to come to New York for treatment, you may want to consult www.clinicaltrials.gov to find studies for PVNS at hospitals that are closer to you. Thank you for your comment.
Christopher
Jul 13, 2016 • 12:45 AM
Thank you in advance for all the amazing work I am learning about !
I have suffered with right knee PVNS for about 16 years now ... I'm finished with surgeries honestly unless so necessary .
And over last 5 years my left knee is suspect !
I am on medicine for pain and inflammation and look forward to being free of that done day without losing quality of life !
I wonder if this trial may still be open or if it may be moving forward !
Thank you in advance , respect
Christopher
Memorial Sloan Kettering
Jul 13, 2016 • 10:59 AM
In reply to Thank you in advance for all… by Christopher
Hi, Christopher, we are sorry to hear about your health issues. We currently have a Phase III clinical trial evaluating PLX3397 for people with Pigmented Villonodular Synovitis: https://www.mskcc.org/cancer-care/clinical-trials/15-074. Please call our Physician Referral Service to see if you are eligible for this or any other clinical trials at MSK. Their number is 800-525-2225. Thank you for reaching out to us.
Barb
Jul 26, 2016 • 12:18 PM
I am 22 you female who has just been diagnosed with DPVNS in my left knee. The oncology orthopedist wants to perform a synovectomy with an open anterior incision. Would this trial be appropriate for me? Should a skilled surgeon be able to perform an arthroscopic synovectomy with the same results? Thank you.
Barb, thank you for reaching out. If you would like to participate in the PVNS trial at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. If you are not able to come to New York for treatment, we recommend going to www.clinicaltrials.gov to find other centers that are offering new treatments for PVNS. Thank you for your comment.
Nenna
Sep 8, 2016 • 6:25 PM
Hi Nenna, we recommend you discuss your questions with a PVNS expert. If you’d like to make an appointment for your son to speak with someone at MSK, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment.
Danielle S.
Oct 21, 2016 • 3:27 PM
Memorial Sloan Kettering
Oct 25, 2016 • 11:54 AM
In reply to I came across this article… by Danielle S.
Hi Danielle, the trial discussed in this post is now closed to accrual, but according to Dr. Tap, others are forthcoming. In the meantime, there may be the option of off-label use of the drug Gleevec. If you are interested in making an appointment to learn more, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment.
Tony Gaines
Oct 27, 2016 • 9:02 PM
I have had two major surgeries to remove my severe diffused PVNS and it has come back aggressively within months. Since the joint is degraded with nothing left, my oncologist is sending me to a radiation specialist. My concern is degrading the bone so I cannot get a full replacement or if a do a replacement the disease eats the glue and I am back to the beginning. Since my oncologist says this is the second worst he has seen and it is back, I am looking for a solution before amputation becomes part of the conversation.
Dear Tony, we are sorry to hear about your diagnosis. If you would like to come to MSK to consult with one of our specialists about possible next steps in your care, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.
SueAnne Green
Dec 15, 2016 • 1:43 PM
I was a participant in the PLX3397 trial forb20 months. I had lots of side effects, the most severe were critically elevated liver enzymes. On 2 occasions, I had to hold the drug until my levels came down. Those 2 times happened within the 1st 7-8 months on the trial. Then on cycle 20, the levels became the highest ever and since this was the 3rd time I had to be removed from the drug. That was 1 1/2yrs ago and I am still having elevated liver enzymes that have cycled from normal one month and then extremely elevated another month. I Have had a liver biopsy and it was determined to be related to the drug. I have also had lingering joint pain and swelling (esp. in my hands). I can say I have yet to feel like my old self even after being off the drug for a yr and half. I can say that related to my tumors in my knee, I did have tumor reduction of 35% and did notice a difference in my knee function. Of course now that I am off the drug my tumors have grown back in size and I am currently waiting as long as possible before I have my 3rd surgery. I say all of this not to deter someone from participating on the drug, but to explain that it is still a chemo drug, which is not easy on the rest of your body and the side effects were a lot harder to overcome even after more than a year off the drug. I am aware that the study moved to phase 3 I think and many participants are having liver enzyme elevations. If you chose to start this drug, please pay very close attention to the side effects.
Memorial Sloan Kettering
Dec 16, 2016 • 2:08 PM
In reply to I was a participant in the… by SueAnne Green
Sarah Carlson
Jan 12, 2017 • 1:58 AM
Hello All, I've read many comments and my story is similar in many ways. My pain and swelling started when I was very young. I saw many doctors across the US and was finally diagnosed when my ortho sent a biopsy from my total knee at the age of 22. I was having similar problems about 3 years later and went in for surgery again. Unfortunately I developed a staph infection and fought it for 6 years. I am now on my 4th total knee. I moved to OR and I've started having symptoms again. I have been trying for the last 3 months to find a doctor that is willing to see me. Everyone I see says it's just chronic pain but my family doctor, physical therapist and I believe it may be a reoccurance of my PVNS. I was hoping you may be able to recommend someone for me in my area.
Memorial Sloan Kettering
Jan 12, 2017 • 10:33 AM
In reply to Hello All, I've read many… by Sarah Carlson
Dear Sarah, we are sorry to hear about your health issues. You might consider browsing through the clinical studies available in your area on www.clinicaltrials.gov. If you are in the New York City area, and are interested in making an appointment to come to MSK, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out to us.
Beth Bridgeman
Apr 10, 2017 • 6:02 PM
Memorial Sloan Kettering
Apr 13, 2017 • 6:39 PM
In reply to I have been diagnosed with… by Beth Bridgeman
Max G. Latham, MD
Apr 16, 2017 • 3:37 PM
My wife, a registered dietician, has suffered 50 or so years with knee PVS and after 25 surgeries and two replacements, still has intermittent flare-up. Most recently we have consulted with our orthopedist and sought a consult with one at Southwestern Medical School, Dallas, my Alma mater, who recommended a bone scan after which he has replied the need for yet another additional consultation. This prompts me to cast about for those having capability to offer some relief short of amputation,
As remote as we are, there is still an interest in seeking help and would appreciate a more proximate therapist.
Personally, I suspect she is a candidate for another arthroscopy, but there is little interest locally for the fear of an infection.
Current status is at a lull, requiring only occasional pain meds.
She is not supposed to use NSAIDS since she has had stem cell injections in the other knee for DJD.
Thanks
Memorial Sloan Kettering
Apr 17, 2017 • 8:57 AM
In reply to My wife, a registered… by Max G. Latham, MD
Dear Dr. Latham, we’re sorry to hear that your wife is going through this. The trial discussed in this study is currently closed to accrual but Dr. Tap expects that a new trial will be opening soon. If you are interested in learning more, we recommend you consult www.clinicaltrials.gov in a few months to find a trial site that is near you. Thank you for your comment, and best wishes to you and your wife.
Max G. Latham, MD
Apr 27, 2017 • 5:28 PM
As a retired FP, recently working the ER and married to a sufferer of PVN for decades who has had two replacements, numerous synovectomies all preceded with radioactive gold injection beginning in the early 60s, I am seeking direction in management of what I think may be recurrent PVS associated with significant pain, intermittent swelling and occasional fluid. We have consulted with our orthopedist, an orthopedist at Southwestern Medical ans her FP. All seem to have no solution.Her last study was a bone scan with vague result.
Is there a consultant in the Southwest or do we need to seek an appointment with dr Tap?
thanks
Max G. Latham, MD
Memorial Sloan Kettering
May 1, 2017 • 9:49 AM
In reply to As a retired FP, recently… by Max G. Latham, MD
Dear Max, we’re sorry to hear your wife is going through this. The trial discussed in this story is closed to accrual, but Dr. Tap expects that another trial will be recruiting soon. It is likely that other medical centers will be involved. If you’d like to find out more, we recommend you contact the company that makes the drug, called Plexxikon, or go to www.clinicaltrials.gov. If your wife would like to have a consultation with Dr. Tap you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information on making an appointment. Thank you for your comment and best wishes to you and your family.
Michael Bigwood
May 22, 2017 • 11:19 PM
Memorial Sloan Kettering
May 23, 2017 • 12:20 PM
In reply to I have been recently… by Michael Bigwood
Dear Michael, this drug is currently available as part of clinical trials only. We recommend that you go to www.clinicaltrials.gov to find out if there are any trials currently open in your part of Australia. You may also want to reach out to the company that makes the drug. Thank you for your comment, and best wishes to you.
Susan Hyde-Wick
Jan 16, 2018 • 11:35 PM
I had my knee replaced in July of 2017 and was doing well until about the 6th month, when I was told I had synovitis. It was described as a growth of the synovial sheath "like a sea anemone" with finger-like structures. For the last month I've had crepitus and pain especially upon extension and it's getting worse I think. I was going to go to the HSS in New York to find an surgeon who specialized in arthroscopic surgery after TKR complications. I found this site. Am I pursuing the correct route? I'm 67, female, very athletic. I was SUPaddleboarding in August and now I'm in pain.
Memorial Sloan Kettering
Jan 17, 2018 • 8:24 AM
In reply to I had my knee replaced in… by Susan Hyde-Wick
Dear Susan, we’re sorry to hear that you’re going through this. When choosing a surgeon, it’s important to talk to them about their experience, and how many times they have done the procedure that you’re going to have. You may want to consider a second opinion with another specialist to make sure you have considered all your options. Thank you for your comment, and best wishes to you.
Michelle
Mar 13, 2018 • 10:50 PM
My boyfriend has been recently diagnosed with PVNS,and he have had a arthroscopic surgery in BeiJing ,China. I really worry the PVNS will recur,and I hope there is any drug like PLX3397 can cure or prevent it. So, can you tell me how can I get the drug ,is it really effective?
Hope to receive your reply ,Thank you very much!
Sara
Jun 8, 2018 • 11:20 PM
My daughter is 35 and has just been told she has pvns. In her right ankle. She has just finished nursing school so she is going to be on her feet a lot. Are there any trials going on in Chicago Ill.? She is a widow with 2 young boys so she really can’t go out of the state. Would really like to see her walk normal again.
Dear Sara, we’re sorry to hear about your daughter’s diagnosis. We recommend she go to www.clinicaltrials.gov to find out if there is a clinical trial for PVNS in your area. She could also consult with a specialist at an academic medical center that has a strong orthopedics department. Thank you for your comment, and best wishes to you and your family.
Marina Fernandez
Aug 15, 2018 • 2:33 PM
I was diuagnosed three years ago and h av had two operations.One in the front and one in the back. My Doctor Haryy Temple here in Miami is very well versed in this disease but since I still have
now again in the back of my knee I am having second thoughts in the knee replacement.
Please advise of that drug that you say it has been very successful so that I can let him know
if he doesnt know already Thank you
Memorial Sloan Kettering
Aug 16, 2018 • 10:56 AM
In reply to I was diuagnosed three years… by Marina Fernandez
Dear Marina, we’re sorry to hear you’ve been through this. If you would like to have a consultation with an expert at MSK to discuss this, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment, and best wishes to you.
James M
Sep 14, 2018 • 4:05 AM
About a year ago, I was diagnosed with PVNS of the knee. The condition existed for a length of time prior to the diagnosis. The pain is now chronic and I need a surgeon right away. I live in East Texas and I need help finding a competent, PVNS experienced surgeon. Do you have any suggestions on how to find a surgeon with PVNS experience? Please help ASPA. Sincerely, James M.
Melinda Pickering
Nov 7, 2018 • 8:52 AM
Hi my name is Mindy, in 2011 I had a tumor PVSN removed from my spine in MAYO at Rochester, in all removal from the pelvis which wrapped itself around my spine deteriorating many vertebrae's which were replaced by donor vertebrae, in all ut was bigger then a football. Since I've had had to have over a dozen lipomas removed. I'm wondering if these aren't actually PVSN tumors. My surgeries for removal & repair were very extensive. I now have Titanium rods in my back with other hardware. I'm currently experiencing more pains and having more removed next week. It took days to be diagnosed due to the location only the neurosurgeon at MAYO would treat it. I just wonder if its PVSN. I wish there was a way to know for sure
Memorial Sloan Kettering
Nov 7, 2018 • 12:07 PM
In reply to Hi my name is Mindy, in 2011… by Melinda Pickering
Dear Mindy, we’re sorry to hear you’ve been through all this. If you would like to arrange a pathology consultation with someone from MSK, you can go to https://www.mskcc.org/teaser/pathology-consultations-healthcare-profess… for more information. They should be able to help you with the diagnosis of these tumors.
Thank you for your comment and best wishes to you.
Josh T.
Dec 6, 2018 • 7:55 PM
I was diagnosed with PVNS in my left knee 5 years ago. The first two synovectomies were front arthroscopic and had them six months apart. I had to make a career change knowing I will have this for life. Things were going fine for the next 4 years until this summer when the swelling and pain returned. The MRI shows that it has returned in the joint and is also wrapping around my hamstring. I live in the Milwaukee area and am seeking care at Froedtert and the Medical College of Wisconsin. I have been under the care of a sports medicine physician and recently an orthopedic oncologist at the same time. I was told today that my case is being referred to another oncologist as well. The first 4 years was flawless with the doctors and now I feel like they are not telling me something or possibly do not know enough about this disease. Any doctor recommendations in the Milwaukee area or a nearby state? I’m 35 and want to do this right. I’m thinking long term and have a long life to live.
Memorial Sloan Kettering
Dec 7, 2018 • 11:55 AM
In reply to I was diagnosed with PVNS in… by Josh T.
Dear Josh, we’re sorry to hear you’re going through this. We recommend that you seek out a specialist at a National Cancer Institute-designated cancer cancer. You can find a list here: https://www.cancer.gov/research/nci-role/cancer-centers
If you’re interested in coming to MSK in New York for a consultation or second opinion, you can call 800-525-2225 or go to https://www.mskcc.org/experience/become-patient/appointment for more information. Thank you for your comment and best wishes to you.
Rebecca, thank you for reaching out. We passed your question along to Dr. Tap, who responded that he does not know anyone in that area with specific PVNS expertise. He suggested making at appointment at MSK. If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at
800-525-2225 or go to http://www.mskcc.org/cancercare/appointment. Thanks for your comment.