MPNforum Magazine

(Transcription, photos, links to full text and commentary on this story can be found at www.mpnforum.com)

We already knew Dr. Ayalew Tefferi, certainly one of the eminences of international hematology, was not happy.

In his letter to the New England Journal of Medicine in October he wrote about the dismal results of Ruxolitinib where 47 of 51 patients dropped out of Phase I/II clinical trials – these are the dosage and toxicity trials — because of either lack of response or .serious adverse events. 18 patients (35%) died and 10% became leukemic.. (For details see The Elephant in the Room section of NYC Goes MPD for the Day )

His objections, based on a small scale study of an informally acquired cohort of Mayo patients, were sufficiently serious for him to raise them publicly in the pages of perhaps the most prestigious medical journal on the planet.

This week he left no doubt where he stands.

In his study of 1000 Mayo Clinic myelofibrosis patients over a period 34 years, using DIPSS Plus,(Dynamic International Prognostic Scoring System for Primary Myelofibrosis) , he concludes Ruxolitinib (Jakafi) is the answer for only about 20% of primary myelofibrosis patients.

In addition to the full article, “One Thousand Patients with Primary Myelofibrosis: The Mayo Clinic Experience, ” published in the Proceedings of the Mayo Clinic (Jan, 2012) and available here, he released a supplemental video to drive home the point. That video can be seen on YouTube .

(We’ve included the full text of his video, below.)

Tefferi concludes his video with a barely disguised slam at the trials and subsequent promotion that have accompanied Incyte’s product development and introduction. Since his Mayo associate at Scottsdale, Ruben Mesa, was a co-principal investigator on Ruxolitinib, the vehemence of Tefferi’s presentation strongly suggests he feels the need to sound some alarms. Fast.

Ruben Mesa told MPNforum ” The randomized data from the international Comfort 1 and 2 trials will soon be published and are very positive studies. The choice of whether a patient should use Ruxolitinib will be between a patient and their physician. All of the published data should be considered in making that decision. “

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Transcription of the Tefferi video:

Greetings. My name is Ayalew Tefferi and I am a professor of medicine and hematology at the Mayo Clinic in Rochester,Minnesota. And I’m here to highlight the key findings in a 1000 patient study in primary MF , a study that is scheduled to appear in the proceedings of the May Clinic Proceedings, issue of January 12.

The study is the largest of its kind and is further distinguished by the fact that over 95% of the patients have had cytogenic information at the time of the diagnosis

The first key finding is the fact that when patients with MF present their clincal features are not at a steady state and usually progress within the first few months of their diagnosis This is not a trivial matter because it affects how accurate prognostication is for each individual patient. In other words it’s best to wait a few months after diagnosis before providing a prognostic score for a particular patient

The second finding is the fact that the most recent revison of the international prognostic scoring system, the so-called DIPPS plus prognostic system, performed much better in discriminating between different risk groups and this is probably because DIPPS + includes cytogenic information in prognostic evaluation.

The third key finding is the fact that many patients with primary myelofibrosis can live a very long life and in fact patients with low risk have an average survival that exceeds 15 years Also …In young patients, even if they are at intermediate risk disease they can can expect a median survival that approaches 15 years. On the other hand, DIPPS + allows us to identify patients in whom survival is shorter than five years and in whom allogenic stem transplantation is most suitable.

The fourth finding is actually important in terms of management and it tells us what proportion of patients with this disease are suitable for what therapy

In general more than 50% of the patients usually present in a manner that requires simple observation alone or utilization of some conventional therapy. Among the other 50 percent only half will have disease features such as massive splenomegally or profound constitutional symptoms that would require an anticytokine therapy such as the newly appproved Ruxolitinib. which is a JAK 1 and JAK 2 inthibitor,

25% of the patients might require consideration of allogenic stem cell transplantation, earlier than later. In other words, the newly approved ruxolitinib in patients with myelofibrosis is proably appropriate in no more than 20% of patients with this disease.

Last and most important conclusion that can be made from our large study is the fact that one has to understand the natural history of a specif ic disease in order to justify a specific treatment recommendation and also in order to design a clinical trial with endpoints that are relevant to patients rather than drug companies,