MPNforum Magazine

The Scientist Physician as Pioneer and Interferon Advocate

He is  Head of Research, Department of Hematology, Zealand University Hospital and the University of Copenhagen founder of the Danish MPN Consortium and the Zealand Inflammation Research Initiative. and a principal investigaor of  major MPN clinical trials He’s also  a much beleoved and busy physian the author of several hundred scientnific paper.Professor Hans Carl Hasselbalch, MD,, the interferon firebrand, is  a brilliant doctor/scientist rich in titles and publications

His support of interferon MPN therapy has had an important impact on current medical practice.  Beyond his deep research and long journal publishing credits (see below) his spirited defense of interferon in treatmetn of MPNs.  Responding for widespread institutional resistance to interferon therapy based on the absence of formal clinical trial —  despite demonstrated resultd– Hasselbalch wrote an Open Letter to Attacks on Interferon that appeared in MPNforum and the MPN Research Foundation website. Over 12,000  patients downloaded that letter, many including it in packages successfully appealing denial of interferon prescription.

He’s worth listening to.

In the 1980s Hasselbalch introduced interferon-alpha2 (IFN) for patients
with MPNs in Denmark.  Since then he’s conducted several studies on the safety and efficacy of IFN in the treatment of MPNs – studies, which have paved the way for IFN being today routine treatment and the drug of choice for younger patients in the early stages of MPNs (ET/PV). And not only he young.

“There is no reason for age discriminationl in using interferon.”

All pts in my clinic are asked if they want to be treated with interferon. Even the elderly, past 80. Two or three handfuls of patients are over 80 and they do perfectly well. They come to me and say hello, Hans, how are you, I am fine. To say that the elderly  do not tolerate interferon is not my experience,.”

But his central message — and it has been for several years 00 has nothing to do with age.  It isn’t hard to reduce the MPN therapeutic approach of Dr. Hans Hasselbalch to a couple of simple conclusions:

• Treat early
• Treat with Interferon

 “We have shown  that MPNs are massively under diagnosed,” Hasselbalch told MPNforum, “perhaps half a million US citizens. and are at constant risk of life threating thrombotic events a and secondary cancers. They present with thrombosis of the brain or elsewhere with reactive white blood cell counts and in some cases elevated platelet counts. It is not common to check for an underlying MPN and thus they continue to be treated at hospital  before the MPN diagnosis.

“This is the most important  research area in our research consortium  that we a lto of resoruces high MPN risk profile patients  neurology colalgues raised oney  phD study  neuroloigts dpet of cardiolgyhis we open the minds of cardiolits eyes of neuroligst to see and pick out those patientwwhich actually have MPNs.

“Future researdh should therefore focus on early diagnosis and early treatment with stem cell targeted therapy (interferon-alpha2) to eradicate the malignant clone.”  Hasselbalch has raised funds to support an interdisciplinary PhD program to bring together cardiologists, neurologists and pulmonary specialits to study underlying thrombotic events stemming from myleoproliferative neoplasm.”

The Early Intervention Concept in The Interferon Era

For decades we have known that IFN is able to induce hematological remissions in patients with ET and PV. In recent years several studies have shown that treatment with IFN is also accompanied by “complete” or major molecular remissions ( as assessed by a decline in the JAK2V617F allele burden) in patients with ET and PV. These molecular remissions are associated with normalization of the bone marrow and are sustained after discontinuation of IFN ( minimal residual disease/operational cure) in a subset of patients. Taking into account that ET and PV are early cancer stages which – left untreated – may progress to myelofibrosis and AML it seems logical to consider early upfront intervention with IFN in order to prohibit clonal evoluti

To put it shortly – MPNs are no exception to general cancer biology – treating a cancer as early as possible is the path towards cure – not “watch and wait “ since then the cancer expands and evolves from the early cancer stages ( in MPNs ET/PV) towards the advanced “metastatic stage “ – the myelofibrosis stage , being characaerized by increasing genomic instability and emergence of several cancer-promoting subclones , resistance to treatment and ultimately multi-organ failure – and death or death due to leukemic transformation.  

On inflammation

In 2012, Hasselbalch published in Blood his hypothesis on chronic inflammation as the driver of
clonal evolution, premature atherosclerosis and second cancers in MPNs. Based upon his significant
work chronic inflammation is today considered a major driving force for disease progression, having likely
great impact on the mutational landscape. An article in MPNforum by Marina Peed addressed his findings. that were presented at an earlier CR&T meeting.

Combination MPN treatment — Jakafi and Interferon

Despite his objection to the use of Jakavi (European designation of ruxolitinib) as a polycythemia vera monotherapy –“This approval of Jakavi this is the greatest catastrophe in MPN history” — Hasselbalach does treat PV with a combination therapy of Jakavi and interferon, counting on Jakavi to treat inflammation and then withdrawing the drug relying on interferon monotherapy to reduce cellular production of the disease. He has documented success in this approach through the achievement of Minimal Residual Disease revealed through bone marrow biopsy persisting beyond five years even after withdrawal of interferon.

Enter HU the old workhorse

“This is a catastrophe that Jakavi has given to PV patients. Instead  of combination with Jakavi we’re startomg another study next year combine interferon with hydroxyurea. because our preliminary data show the comibnation works very well. We should be able to decrease dosage of both interferon and HU combining the two old horses pf tje last 30 years.  We s submitted  the protocol two weeks ago and believe  this combination is perfect. We have rapid decline by HU followed by INT  replacing highly expense drug that gives rise to infections and requires lsots of investigations and followup.” 

On a final note:

After we commented how well he looked on the ZOOM scren, just as fit and young as he did years ago when we first met.  Hasselbalch said, “I have two families my smll famoly and my huge MPN family.  I live my normal lovely life with red wine on the weekend and running, running on the weekend.   I had my 70 years birthday Augst 30 and I will continue tp  fight for my lovely patients world wide

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