Science & Medicine

Tefferi Drops the Other Shoe

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. “

   +++++++++++++++         .

 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 probably 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.

Contents: January 2012:(Click on RED link )

Articles:…Marty’s Stem Cell Transplant …..My Robert ….Sevy’s Ride … ..Manuela’s Journey……Drop the “D” Crisis in MPN Care….Nearly Painless BMB….News Briefs .

Columns: The Empowered Patient ….The Long and Winding Road..:..Jeremy’s MPN Life :… Body-Mind-Spirit and Prayer ….
Arch’s Corner .

Join Your MPN friends at the Forum

(If you prefer hard copy, there is a PRINT/PDF option at the end of each article.)

Raise your voice in the Forum, COMMENTS box after each article.

Take me back to the Contents

© Zhenya Senyak and, 2011. Unauthorized use and/or duplication of this material without express and written permission from this blog’s author and/or owner is strictly prohibited. Excerpts and links may be used, provided that full and clear credit is given to Zhenya Senyak and with appropriate and specific direction to the original content.

Comments on: "Tefferi Drops the Other Shoe" (1)

  1. LInda Speen said:

    I am seriously worried about my sister, who is strongly considering taking this rx. as the first patient her dr. has had to do so. If only 20% of patients would benefit from this drug, I sure hope she is in the 20%, She has no other alternative, as she is elderly. I would appreciate hearing from anyone who can venture any hope or experience!! Thank you much and God Bless.

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