The moment of truth
- – Zhenya Senyak
Some decisions are too important be made based on posts, tweets or sound bites. With our quality of life, longevity and survival in the balance it makes sense to review the evidence. This Special Report contains testimony of MPN patients and some of the world’s leading MPN specialists on the risk/benefits of hydroxyurea and interferon.
In the first week of December, the results of three large clinical trials comparing the impact of hydroxyurea (HU) and interferon (INF) on our health and quality of life will be presented at ASH. For ET and PV as well as MF, these are our workhorse drugs. There is no event more relevant to the actual therapeutic choices we face as MPN patients.
Despite real innovations in development – notably gene therapy and immunotherapy – right now and in the near-term future we have no radical alternatives to HU and INF for treatment of polycythemia vera and essential thrombocythemia. These two drugs, neither of which is FDA approved for use in MPN therapy, are prescribed at one time or another, alone or in combination, for the great majority of MPN patients. (The myelofibrosis drug Jakafi, recently FDA approved for PV patients, remains a controversial expensive alternative, alone or in combination with other drugs.)
This Special Report on HU vs INF brings fresh input from patients and physicians to help inform a potentially life-altering decision in advance of the ASH meeting at which some hard data should emerge. For the significance of these clinical trials, see the video of Dr. Claire Harrison and Dr. Ronald Hoffman talking about their importance.
You can access each patient experience and expert specialist opinion in this Special Report right here:
ET patient Elizabeth Goldstein reports on how Pegasys both failed and sickened her.
ET patient Barbara Kurtz writes about her 30 year control of ET with hydroxyurea.
Jeremy Smith, an MF post polycythemia vera patient makes a passionate plea for mindfulness that can save your life.
In the MPN Specialists’ view, Drs. Ruben Mesa, John Mascarenhas, Jerry Spivak and Brady Stein join the discussion with with their combined heavy MPN experience from the clinics of the Mayo Clinic, Mt. Sinai, Johns Hopkins, and Northwestern . (Dr. Hans Hasselbalch comments on Elizabeth Goldstein’s report. )
Beyond direct testimony from patients and specialists, in this Special Report we present pricing and selected published resources to help us determine which of these two frontline drugs for high risk ET/PV might be most effective for each of us.
How to use this Special Report: We urge you to actively review this Special Report, so you can advocate for yourself. Take notes on the professional opinions expressed here that apply to you. And take patient stories to heart. Share relevant material with your friends, family, and physician. As Jeremy Smith puts it, “This may save your life.”
Context and trials
The Lone Ranger and the Silver Buckshot
Our two main drugs, hydroxyurea and interferon, work more like a load of buckshot than a silver bullet for our MPNs. But for now and in the immediate feature they are the best we have. At best either of these drugs can help us. At their worst, hurt us. We need to know the real risk/benefits of each.
MPNs are a genetic disease. The various MPNs all start with a mutation in a gene coding for our blood producing stem or precursor cell. This leads to a cascade of events including — but not limited to — downstream mutations, shifts in cytokine signalling, proliferating cell production. Even if our physicians knew our complete genotype, every gene, our completely sequenced DNA, applying a med based on our genotype to block the impact of the initial mutation is not likely to effect a cure. Although INF can lay claim to restructuring of the marrow and complete remission in some cases, so far only a stem cell transplant can do that, and that’s not an option for all of us.
Like every other drug on the market, neither HU nor INF deals with the cause of our MPN. Each – alone or in combination with other drugs — effectively alleviates some of the effects, in radically different ways. For a time
And there are complicating factors that limit the predicted effectiveness of HU and INF. Epigenetics. the genetic distortions caused by stress, disease or chance can determine which genes are expressed or shut down. Another complication is our microbiome.
While the traffic and commotion generated by our own trillions of cells is beyond our current understanding or control, we are host to an equal number – some say a far greater number – of other life forms in our microbiome. Not just the foreign inhabitants of our gut, but all those life forms in us and on us, viruses, bacteria, fungi and archaea. These hangers-on, these passengers and microbic workers, some good, some evil, some neutral have no interest in us beyond their own life support…and yet they affect the way we think, age, dream, respond to food and meds, sicken and die.
To treat essential thrombocythemia or polycythemia vera, our physicans have to largely ignore all this and focus on the physical signs of our disease using a gigantic sledge hammer to go after an invisible molecular process unfolding in the darkest recesses of the hematopoietic stem cell’s nucleus. The process is going to smash up a lot of innocent bystanders and interrupt other cellular business whizzing around our bodies. But we can within limits, stop DNA repair, support the immune system, block the JAK-STAT pathway and throw a wet blanket on blood cell reproduction… for awhile.
And that’s where we are when we’re offered hydroxyurea or interferon. One or the other will likely work for some of us, some of the time. Our age and risk status will certainly be taken into account but our choice boils down to determining which is likely most effective for us while posing the lowest short and-long term risk. Another non-medical factor is relative cost and the frequent need to battle for insurance approval of interferon — at the cost of several thousand dollars per months vs, hydroxyurea’s under $100 monthly tab.
The current trio of comparative clinical trials comparing the two drugs – AOP Orphan Pharmaceutical, the Danes, and MPD-RC – might help clarify the decision-making process. All three will report results at ASH and present posters. It’s unlikely anything that comes out at this meeting will be a game-changer. And the results will not be surprising. AOP didn’t spent millions of dollars to prove its variant of pegylated interferon is not effective. The Danes have been using interferon successfully for decades. And the ambitious but incompletely enrolled 30 country MPD-RC trial will have only partial, provisional data to report.
See the Addendum to this report for details on relative drug pricing and the specific clinical trials we’ll be focusing on at ASH.
© 2016, MPNforum. All rights reserved under Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License