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
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:
Allogeneic Stem Cell Transplantation for Primary or Secondary Myelofibrosis: A Retrospective Intent-to-Treat Analysis and Impact of Mutational Status and JAK1/2 Inhibitor Ruxolitinib Prescription in Patients Who Cannot Proceed to Transplantation
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.
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