MPN’s, Marathons, and New Friends
by Jamie Strause
I arrived in New York City in the wake of the New York City Marathon in order to attend the Seventh International Patient Symposium on Myleoproliferative Neoplasms. The city was still abuzz in the aftermath of the Marathon which stretches a grueling 26.2 miles from its start in Staten Island through many neighborhoods along its course, finally ending in Central Park.
Participating in the marathon represents an effort to achieve your personal best along with sheer perseverance. There are many twists and turns, triumphs and defeats, and periods of exhaustion, alternating with bursts of energy along the way.
As I signed into the conference, I couldn’t help but think that having an MPN is very much like running a marathon. MPN’s span decades and are also punctuated by many twists and turns along the course of a lifetime. I thought that perhaps they should give us all race bibs instead of nametags. I sat down and prepared for a marathon session of information, hoping for some miraculous new information that would propel us all to the finish line…..
Mile 1 to 2 (Staten Island to Verrazano Narrows Bridge)
The marathon session started with a lecture by John Crispino, PhD from Northwestern University on New Concepts in Basic Biology of MPN’s. This was a very technical discussion about the myriad of mutations that are involved in the MPN’s, with a particular emphasis on myelofibrosis. The top three spots are held by JAK2, ASXL1 and TET2. Many mutations have been identified but there are likely many more at play that have yet to be identified. Indentifying mutations in a particular patient may help to better predict prognosis and individually tailor therapy. The good news is that many mutations may equate to multiple targets for therapeutic intervention in the future.
The next lecture was by Ronald Hoffman, MD from Mount Sinai Medical Center on What is the Value of Epigenetic Therapy in MPN Treatment? E-p-i-g….what? Epigenetics is “the study of heritable changes in gene expression that are not due to changes in DNA sequence. “Epigenetic changes are crucial for the development and differentiation of the various cell types in an organism.” The experts are working on epigenetic therapy directed against cancer progenitor or stem cells, but it is still in the very early stages. Dr Hoffman emphasized that Phase III trials must be completed before any drug or combination of drugs become the standard of care for MPN patients because they deserve an evidence based approach to treatment.
Mile 3 to 9 (Brooklyn to Fort Greene/Clinton Hill)
I started to get my second wind during this part of the marathon ….maybe the endorphins kicked in, or possibly the three cups of coffee that I guzzled earlier. I was very amped up about the next lecture by Jerry Spivak, MD from Johns Hopkins University School of Medicine entitled Can Genetic Analysis Predict MPN Progression? I believe that one of the core issues is determining whether a patient has indolent or aggressive disease. If disease is indolent then conservative therapy would be appropriate; if aggressive disease, then more aggressive treatment would be appropriate.
There was a long and interesting discussion about gender differences in the MPN’s and that “women are not small men” and therefore gender differences need to be taken into account. Women with PV dysregulate fewer genes than men (251 as opposed to 535); there are 102 genes concordantly dysregulated in both men and women.
From the 102 core gene set, Spivak and his colleagues have developed a 10 gene panel to determine aggressive from indolent disease. Unfortunately, this panel is not yet ready for widespread use….there goes that endorphin rush but we all trudge on to the next leg of the marathon…..
Mile 10 to 14 (Bedford-Stuyvesant to Queens)
We all broke to hydrate then heard Srdan Verstovsek, MD from MD Anderson Cancer Center present an Update on JAK2 Inhibitors. Counterintuitive to what one would think, JAK2 Inhibitors are NOT selective for mutated JAK2V617F enzyme and they benefit patients with and without the JAK2V617F mutation. Elimination of disease with the JAK2 inhibitors is unlikely. Lowering of platelets and RBCs is an expected side effect and the drug should not be stopped because of these side effects, the dose should be appropriately adjusted. If the drug is stopped, symptoms return to baseline in 7-10 days. For some reason, that was startling information for me and others.
Dr Verstovsek emphasized that JAK2 Inhibitors are excellent therapy for disease related symptomatic splenomegaly and/or general constitutional symptoms (weight loss, night sweats, etc). He is also hopeful that they may contribute to prolongation of life in patients with advanced disease. He shared some very compelling and emotional patient pictures before and after the start of treatment.
Oh, and in case Incyte thought it would be the only JAK2 inhibitor in the race, there are about 9 other agents in the drug development pipeline.
Next up: Can We Prevent Progression of the MPN’s with Interferon? by Richard T Silver, MD from Weill Cornell Medical Center. Dr Silver emphasized that the type of interferon used doesn’t matter (no difference between Intron and Pegasys). Interferon alpha has many activities including antagonizing various growth factors, inhibiting small vessel growth, inhibiting megakaryocytes (which lead to bone marrow fibrosis), influencing JAK-STAT signaling and inhibiting PV stem cells in the bone marrow. In his opinion, IFN is the “ best treatment option in PV when used in early stage disease.” Also effective in early MF but not if spleen is markedly enlarged or in advanced stage MF.
Mile 15 to 19 (Long Island City to East Harlem)
Unfortunately, Ruben Mesa, MD of the Mayo Clinic in Arizona could not be present due to a health issue but delighted us with an audio voice over of his slide set that he likely prepared from his hospital bed (now that is dedication !). We learned about a variety of different cacti and What Can I Expect From My MPN Treatment? I think I must have become delirious here because I don’t have many notes but Dr Mesa discussed Evolving Prognostic Scales and the MPD-RC trial comparing PEG INF to Hydroxyurea.
Mile 20 to 22 (The Bronx to Harlem)
Babette Weksler, MD from Weill Cornell Medical College lectured on the question Should I Take Aspirin, Plavix, or Coumadin? The main take away message from this lecture was that MPN treatment decreases thrombotic risk. Lowering hematocrit to normal (men < 45% and women < 42%) decreases blood viscosity (thickness) and improves blood flow. Lowering platelets and WBC’s decreases risk; Interferon and HU help to normalize blood counts. JAK2 inhibitors have not been shown to decrease thrombosis rates. With PV and ET, low dose aspirin recommended. IF there has been a venous thrombosis, Coumadin is recommended. No data exist for newer agents (Plavix, etc).
Mile 23 to 26 (Fifth Ave to Central Park South)
Talk about an adrenaline rush at the end…..The Moderated Q&A session with all of the experts. What became abundantly clear during this session was the ongoing lack of consensus among the experts. It is disheartening for patients and caregivers to witness such variability in opinion on the treatment of their disease. Understandably, there is a push for evidence-based medicine obtained through the gold standard, Phase III blinded randomized controlled clinical trial, but will that ever happen in a rare disease with small numbers of patients? And what do patients do in the meantime until the trials are complete? Decide on a treatment based on anecdotal evidence only? Wait and watch? Drop out of the race? All difficult and unanswerable questions.
Mile 26.2-The Finish (Central Park)
Tariq Mughal, MD from London gave an impromptu and very impassioned speech about the cost of drugs and our need to improve access to medications on a compassionate basis. I think I saw the Incyte reps squirming in their seats.
Andrew Schafer, MD was announced as the Director of the Silver MPN Center at Weill Cornell Medical College. He emphasized Transitional Research – taking important findings from bench (lab or basic research) to the bedside and vice versa. Some of the other goals of the Center are to expand clinical trials and offer a broad based interdisciplinary approach to the MPN patient for the greater good of patient care.
One of the most enjoyable parts of the conference was meeting new friends. To name a few: Jason Rappaport, Cary Gruber, Michael Mursten, Samantha Trahan and Mary Cotter (who I had a difficult time finding because she looks nothing like her facebook profile picture). I felt Peggy Zampeti Frederick and Pat Drennan Malavasi in the room but never got to meet them.
I think the most important take home message for me is that this disease is like a marathon. There are ups and downs. There are twists and turns. There is triumph and defeat. It takes perseverance, and there is time…there is time to be thoughtful, weigh the options and make the best decision for yourself. And most importantly, you are not running the race alone.
Dinner and a Show and a Symposium
By Mary Cotter
It was an opportunity to put a little romance into a 25 year relationship when I asked my husband if he would like to play hooky from work and take a mid-week break to NYC, go out to dinner and see a show on Broadway. Of course! Sounds like fun! He says. Oh, by the way dear, I want to meet up with some online friends at this little conference called the 7th International Patient Symposium on Myeloproliferative Neoplams. There is this group of doctors who will be presenting their latest research and thoughts on the treatment of MPNs. It will be FUN!
I made the arrangements. Amtrak tickets. Hotel reservations at the JW Marriott Essex House overlooking Central Park. (Swanky!!!) Orchestra seats at the Gershwin Theater for Wicked. Dinner plans to be determined. And of course registration for the Symposium at the New York Athletic Club. The mood was set!
We arrived at Penn Station Tuesday mid afternoon, just in time to check into our ultra luxurious hotel room. Very chic, chic! Rest, relax and freshen up before deciding where to go for dinner. The hotel concierge suggested an authentic Brazilian steak house in the Theater District named Churrascaria Plataforma Rodizio. Succulent fine meats cooked to perfection and carved table side.
After that incredible meal it was off to the Gershwin for Wicked. My favorite movie of all time is The Wizard of Oz. The life lessons on searching for one’s heart’s desire and discovering one’s personal power played out in techni-color by Dorothy and her little dog Toto. Wicked too, did not disappoint, lessons on friendships, love, and the real meaning of good vs. evil skillfully woven as a familiar back story to that all time favorite.
Then back to the swanky hotel to listen to the sounds of a gentle bossa nova just like Petula Clark sang about so long ago.
A Day at The Symposium
The day began just as the sun peeked over the skyscrapers with John Crispino, PhD presenting research that suggests there are other mutations at work with Jak2. New names for us to remember include the ASXL1, TET2 and SRSF2 mutations. Patients with more severe disease may have more of these additional mutations.
Dr. Ronald Hoffman, MD helped us understand the concepts of epigenetics and genetics. The old nature vs nurture question. In other words can new medications be developed that change the environment genes live in? And if that environment is changed, can the natural progression of MPNs from MF to AML be halted? His conclusions are that epigenetic therapy is very experimental and in the early days of study but shows promise.
Dr. Jerry Spivak followed up these presentations with his talk on Genetic Analysis to Predict MPN Progression. He pointed out that clinical perspectives about these diseases called myeloproliferative neoplasms continue to be driven by unproven assumptions made 50 years ago! Dr. Spivak went on to say that the disease gene type plus the patient’s genotype creates the individual disease. The context of the patient affects the disease expression. Interestingly he says there are multiple forms of PV. That PV in men is different from PV in women. He also showed research his team conducted where they found a group of 10 genes that increase the probability of aggressive PV. Those without these 10 genes have a more indolent variation of PV.
All of that before the coffee break!
Feeling refreshed we were ready to hear Srdan Verstovsek, MD provide us with an update on Jak2 inhibitors. Big spleens seen in patients with MF can be reduced in 2 – 3 months with Jak2 inhibitors. These drugs work on both Jak2 positive and Jak2 negative patients. He showed photos of patients with obvious dramatic improvement in physical health and quality of life as a result of Jak2 inhibitor therapy. Patients who were close to their final chapter once again able to travel, walk and enjoy life due to the benefits of Jak2 inhibitor therapy. Jak2 inhibitors do not eliminate the disease however.
Dr. Richard Silver discussed whether we can prevent progression of MPNs with interferon. He talked about the effects of interferon on each of the MPNs, ET, PV and MF and the importance of an accurate initial diagnosis because these diseases overlap and appear to mimic one another. His basic message is YES, interferon can prevent progression of disease when used early in the disease.
Dr. Ruben Mesa was unable to attend the symposium due to a personal health crisis but did deliver his presentation virtually. He too pointed out the progressive nature of MPNs and the importance of symptom relief for patients. Dr. Mesa’s presentation described the psycho-social aspects of the burden of symptoms and the stress associated with having a rare disease.
Lastly Dr. Babette Weksler worked hard to help us answer the question whether we should take aspirin, Plavix or Coumadin. She described how blood cells work to cause a clotting or a bleeding event and the mechanical nature of the activity within our arteries and veins. Her advice is keep it simple. There really isn’t enough data on treatment with newer anti-coagulation therapy to prove it is any more effective than a humble little baby aspirin. In fact she urged much caution with the use of the newest anti-coag drug Zarelto because unlike Coumadin, there is no antidote to reverse a major bleeding episode in a patient on Zarelto.
By this point in the day my head was spinning. So much information and how I regretted not studying more in my college biology classes! It was a huge relief when David Boule announced that all of the power point presentations and a video of the Symposium would be posted on the CR&T website.
The Important Stuff
The nature of any big event such as the Symposium can be very dry to those of us who are not professionally schooled in medicine and the biological sciences. I know I cannot adequately explain these complex topics so I do recommend visiting the CR&T website for those wishing I had taken better notes.
For me, the important reason to attend these conferences is to bring patients together to share the warmth of a real hug, not just a virtual <<<hug>>>. To hold the hand of someone who was terrified of a new MPN diagnosis and now see a wave of calm settle upon their face. To create a true friendship from one born in the virtual world. Meeting Jamie, Jason, Carl, Peggy and Pat was truly worth the price of admission.
Another unexpected pleasure for me was the chance to share a table with Barbara Hoffman and Dr. Ann Hohenhaus, DVM from Animal Medical Center in NYC. These wonderful women not only have a sincere interest in the science of myeloproliferative neoplasms but are passionate about exploring the similarities between veterinary oncology and human oncology. Veterinary medicine and research has so much to teach us about the natural progression of diseases that impact both species. A new and lasting friendship was created from a most unlikely source.
So honey, how about another romantic get away to NYC in November 2015?
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