On Jakafi, transplantation and mutations… a Confession
In the first week of January I woke up in a surgical recovery room at Duke Medical Center to find out a good friend did not survive his stem cell transplant. He and I had walked through an end-stage door at the same time. On Jakafi his myelofibrosis had transformed to acute myeloid leukemia. My odds of survival with Stage 3 colorectal cancer were a little better. But he was younger, stronger and had a questing spirit.
There would be no joy in my recovery. Just a cloud of grief and sadness that extends to this day. After years of regular schmoozing over the Internet backyard fence – and some memorable meetings in the material world – a curtain had descended, sealing off my contact with my brother. It was not the first time. Our community has lost many friends for the same reason: Delayed entry to stem cell transplant.
As Dr. Ruben Mesa said… “Anyone who tells you that the issue of whether or not to have a bone marrow transplant is a simple decision is an individual not facing that decision.”
I have no illusions about stem cell transplant, its promise and pain, its guaranteed risk and hoped for reward. But I know with absolute certainty our odds of success soar in our favor
when we start early rather than late in the game. When we start before all else fails. And, for now, I also know it is our only potentially curative option.
Personally, I don’t qualify. I’m intermediate-2 myelofibrosis but I’m also 81 years old. Not only not qualified but in my own mind not justified. So while I might question my own editorial methods in focusing on the high cost of SCT delay, I don’t question my motives. I want to help create greater awareness of the need for an early SCT preparation.
So much for justifications, on to the confession. It has to do with the MPNforum Special Report on Jakafi and its suspected role in enabling the emergence of deadly mutations
The confession
In this twittery, nervous world, our thumbs dancing over our smart phone keyboard, headlines matter.
We text, we post, we briefly scan the tsunami of information daily pouring all around us. We rely on short bursts of words, Sentence fragments & abbrev. OMG. Headlines matter.
So a headline that starts “Clonal evolution and outcomes in myelofibrosis,..”and goes on for a bit wouldn’t draw most of us in. Even if we did subscribe to the scientific journal Blood which we don’t. That means this important study, the work and its conclusions had been totally lost to us…and to many of our non-MPN specialist docs.
But a headline that asks “Does Jakafi contribute to deadly mutations?” and adds the graphic of a smoking gun is likely to draw us in for a minute or two. For a quick look. And a Facebook post announcing the Special Report on “the hidden menace of the life saving face of Jakafi” was designed to bring in readers.
Problem is the story about mutations was a platform to talk about Jakafi’s role contributing to SCT delay. Many of us skim, few of us read carefully. The Special Report itself is accurate. Fact checked and approved by the authors of the original study in Blood. Even the headlines are true enough. (I do believe Jakafi has a role in helping mutations arise in MF patients.) Both Dr. Srdan Verstovsek and Kate Newberry don’t believe so. But even they aren’t sure. That’s all spelled out – with reasons to back up beliefs – in the Special Report.
So what? Nobdy is reading that far. People aren’t taking notes, they’re taking sides.
I was disingenuous in focusing on mutations. I knew the “hidden danger” I wanted to talk about was Jakafi’s unquestionable ability to make most MF transplant-qualified patients feel better and, as a result, enable them to resist entry to the pain and isolation of stem cell transplant just a little longer.
It can be a fatal illusion. So if the specter of deadly mutations would help increase awareness and encourage an earlier more successful SCT outcome, why not lead with that part of the story?
For a couple of reasons.
“I’m scared. I just started Jakafi.” That was the note from a friend, someone I’ve known from the beginning. She’s lively, intelligent, energetic and, because of my presentation, scared.
The Special Report rocked the MPN boat. In the first days, more than 5000 of us visited that page on MPNforum alone… and the Facebook sites and the MPN Research Foundation newsletter reached an even greater audience. What I hadn’t considered was the impact on patients – friends – who were on Jakafi and had no path to stem cell transplant. As MPN patients we have enough issues on our plates without having to deal with something new and frenzied.
Focused on the unnecessary deaths from delayed SCT I managed to add to the burdens we carry.
I am truly sorry about that.
So here, as an act of contrition, let me pass along some good news about Jakafi for MF you might have missed, news for patients not heading for SCT…and some who are.
In a 2013 paper in Blood, some of the heaviest hitting MPN specialists – Passamonti, Harrison, Vannucchi, Barbui, Gisslinger, Cervantes and others concluded Jakafi can add months to the lives of MF patients and may make a difference in the course of the disease.
Patients receiving ruxolitinib had longer survival (5 years, 95% CI 2.9-7.8, versus 3.5 years, 95% CI 3.0-3.9) with a hazard ratio of 0.61 (95% CI 0.41-0.91, P=.0148). This observation suggests that ruxolitinib may modify the natural history of PMF.
And a 2015 study, also in Blood established the benefits of Jakafi even for High Risk MF patients not on the SCT pathway:
Conclusion: Allo-SCT remains a valid strategy for high-risk MF patients with unfavorable karyotype, high DIPSS+ score and secondary MF while impact of mutational status and JAK2V617F burden have to be confirmed in larger studies. MF patients who cannot proceed to transplant likely benefit from JAK2 inhibitor prescription.
Final note: Help is on the way: MS3T
A group of MPN and transplant specialists, MPN patient advocates and SCT survivors have formed a Taskforce to explore the roots of SCT delay and create programs to improve timely entry when appropriate.
The Taskforce — the MPN Stem Cell Transplant Timing Taskforce (MS3T)– includes Hematologists Dr. Claire Harrison, Dr. Nicholaus Kroger, Dr. Ruben Mesa, Dr.Richard T.Silver, Dr. Srdan Verstovsek Transplant specialists Dr. Andrew Artz, Dr. Koen Van Besien, Dr. Jeanne Palmer, Dr. Uday Popat, MPN SCT Patients Chris Harper, Beatrice Larroque, Martin Prager, and MPN Patient Advocates Ann Brazeau, Ann Haehn, Zhenya Senyak, Barbara Van Husen and Michelle Woerhle.
© MPNforum, LLC , MPNforum.com, and the MPNforum Quarterly Journal 2018. MPNforum is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Reproduction is permitted provided full and clear credit is given to authors and MPNforum.com with appropriate and specific direction to the original content.
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Comments on: "On Jakafi, SCT and Mutations… a Confession" (11)
I don’t understand why you talk only Jakafi for MF. There are other treatments also.
At progressing or later stages of MF, when there is still an SCT or med alternative, there really are no alternatives commonly available to patients. Our focus on Jakafi, the most heavily promoted drug in the MPN formulary, was explained in the article’s large type blockquote:
“I knew the “hidden danger” I wanted to talk about was Jakafi’s unquestionable ability to make most MF transplant-qualified patients feel better and, as a result, enable them to resist entry to the pain and isolation of stem cell transplant just a little longer.”
See: https://mpnforum.com/jakafi-the-other-face/
At progressing or later stages of MF, when there is still an SCT or med alternative, there really are no alternatives commonly available to patients. Our focus on Jakafi, the most heavily promoted drug in the MPN formulary, was explained in the article’s large type blockquote:
“I knew the “hidden danger” I wanted to talk about was Jakafi’s unquestionable ability to make most MF transplant-qualified patients feel better and, as a result, enable them to resist entry to the pain and isolation of stem cell transplant just a little longer.”
See: https://mpnforum.com/jakafi-the-other-face/
Zhen, you know how much I care about you and have depended on your knowledge for years. You know me…I always have questions. What your article did do for me, was prompt me to take it to my doctor. As a result, we had a very open discussion. It did let him know once again that I do not just sit back. I do my best to stay informed on my disease and I expect the same of him….so thank you! All is good!
Between the holidays and deadlines I missed your Comment, Jan. Sorry. Glad you had “the Talk.” Establishing working parameters with our hard-pressed docs is essential. And letting him or her know you’re not a passive partner but plan to actively participate in your therapy can only be a good thing. You’ve always been active, from starting the Carolina Support Group to cheering us on — or jeering when called for — from the sidelines. Glad you plan to remain spunky, Blondie.
Zhen,My condolences to you about losing your good friend. Zhen, you are my greatest hero in the world of myleofibrosis.
Thank you so much for all you have done and thanks so much for “owning up” by your Confession/ aplogy. It has helped clear up
the issues you have raised.
You say, “our odds of success ( for SCT) soar in our favour when we start early rather than later in the (SCT) game.” and feeling good on
Jakafi may hinder an earlier start. AGREED!
BUT, knowing this I do not want the SCT ( with splenectomy..ugh!) that was offered me almost one year ago.
I am 70 and have PMF with huge spleen on Jakafi since September 2013 ( 4 1/2 years). So far, I’m my case, my quality of life this past year has been good , much better than if I had a SCT. I am willing to live with MF or AML and go to the end of my life with “the devil I know”. I have been waiting now impatiently( 6 years) for another FDA approved Jak 2 inhibitor. or better still another type of drug the can smite MF. Happy Passover and Easter. Joy and Peace to all, David J. Macdonald
Hi, David and thanks for the kind remarks. I think your attitude clearly expresses the major reason so many of us avoid stem cell transplantation.
SCT is a deeply personal decision and we can opt out for an infinite number of reasons. My hope is our decision process is driven by careful consideration of our life’s circumstances and the particular and specific risks and benefits in our personal case….and not on hearsay or groundless concerns. Ultimately it’s more than a rational choice based on a physiologic decision matrix but an emotional, social and spiritual decision as well. And it’s a dynamic choice, capable of change in response to circumstances. To paraphrase Dr. Mesa: SCT is a simple decision only to those not facing it. Don’t write off the option just yet. The Reduced Intensity Conditioning regimens have had great success.
All that said, willingness to let go and play the hand you’ve been dealt has a lot to recommend it…unless you have the option to discard some low cards and draw an improved hand. But who knows? In our case the deck is mighty slim. It sounds like Jakafi has stopped working for you which is normal for the course after some years. It’s worth sitting down with your hematologist to review new options, including stopping Jakafi for a time. Did you ever read War of the Clones? It describes the process through which Jakafi temporarily becomes ineffective and might be rejuvenated.
You’re probably young enough to see the application of gene therapy and immunotherapy in MPNs. It has already happened in the liquid cancers, notably acute lymphoblastic leukemia. We just have to unlock a few additional progenitor cell mysteries but we’re getting close. And then there’s the horde of JAK inhibitors likely to rovide symptomatic relief, So yes, enjoy your life but do keep reviewing your options, on your own, and with your hematologist. Good luck, keep in touch.
I still think your frightening headline was a needless sensationalism. I read articles about this disease, with or without the catchy headlines because I know it is deadly serious and I have it. An article after the fact to soften that blow is not going to undo it. I’m a retired teacher. Young children would often hit, then apologize.
Of course I regret anyone feeling fearful unnecessarily. But I think you may have misread my apology, Judith. The Special Report Headline you found sensational was simply a question: Does Jakafi contribute to deadly mutations? Those who actually read the full Special Report realize (1) Jakafi has a vital place in MF therapy; (2) Jakafi contributes to SCT mortalities by its very effectiveness in relieving symptoms, contributing to delayed SCT; (3) I, and others, believe Jakafi does play a role in disrupting the mutational environment and contributes to the emergence of mutations; (4) Dr. Verstovsek and Kate Newberry PhD disagree. They believe it doesn’t but admit the possibility.
I apologized for using the issue of mutations to attract readers in order to call attention to the tangential problem of death due to delayed entry to SCT. And I expressed regret for not providing links to papers with findings useful to MF patients who don’t qualify for SCT for one reason or another. (That was corrected in the Confession.) The mortality caused by SCT delay is simply a tragic fact and not enough of us are aware of the danger. And while I am indeed sorry to have added concerns to anyone’s burden, I can only repeat the Report is entirely factual, fully fact-checked, truthful and, for those of us with myelofibrosis, well worth reading all the way through. I hope, on reflection, and rereading the material, as a retired teacher you will raise my grade from an F to at least a C.
Thank you, Zhenya, for this addendum to your original article. It is just what we needed.
Thanks, Dave… I’ll take that as Apology accepted.