MPN Expert Ruben Mesa on the Anemia-Based Data at ASH

At the 59th American Society of Hematology (ASH) Meeting and Exposition, Rare Disease Report caught up with Ruben Mesa, M.D., Director of the University of Texas Health Cancer Center.

In this video, he discusses the common problem of anemia that can come with myeloproliferative neoplasm (MPN)-associated myelofibrosis, how some of the medications administered can induce it, and the data pertaining to it that was presented at ASH.

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Incyte Reports Four Year Phase 3 Data Analysis Shows Durability of Response of Jakafi (ruxolitinib) in Patients with PV

Incyte Corporation (NASDAQ: INCY) today announced new 208-week (4-year) follow-up data from the ongoing, global, multi-center, open-label Phase 3 RESPONSE study of Jakafi® (ruxolitinib) comparing the efficacy and safety of Jakafi with best available therapy (BAT) in patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU). The pre-planned data analysis showed a durable primary response to Jakafi in patients with PV who are resistant to or intolerant of HU and the overall safety profile for Jakafi remained consistent with previously reported 80-week RESPONSE data.1 The results were shared in an oral presentation today at the 59th American Society of Hematology (ASH) Annual Meeting 2017 in Atlanta, Georgia.

“With 30 months of additional follow-up, the four-year RESPONSE data analysis presented today at ASH further reinforces the potential of Jakafi as a long-term option for patients with PV,” said Peg Squier, M.D., Ph.D., Head of U.S. Medical Affairs at Incyte. “Given the few treatment options available to treat this chronic and progressive blood cancer, these long-term safety and efficacy data are meaningful to patients with uncontrolled PV.”

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Blog: Living in Paradox

November: You Are Not Alone

By Marina Sampanes Peed

When people with a MPN gather, it is easy to forget that these blood cancers are rare. MPN advocates from two dozen countries describe patient experiences that are eerily similar:

  • Correct diagnosis follows one or more years of signs or symptoms.
  • Clinician who made diagnosis did not provide current information about the disease nor treatment options. (Some discount while others magnify the risks.)
  • Delayed in receiving appropriate treatment.
  • Many “Quality of Life” symptoms are not recognized and remain untreated, especially in women.
  • Access to and participation in clinical trials is difficult.
  • Support from the MPN patient community is highly valued.

Most hematologists rarely, if ever, encounter a patient with a MPN. Because the diseases manifest differently, experience with a few patients is not sufficient to develop expertise. If your local physician is not proactive, you may insist he/she confer with a MPN specialist regarding your care. The experts regularly consult with general practitioners and hematologists regarding management of their MPN patients.

If your local physician is not proactive, you may insist he/she confer with a MPN specialist regarding your care. The experts regularly consult with general practitioners and hematologists regarding management of their MPN patients.

The patient experience was a recurring theme in Frankfurt am Main, Germany October 27-29, 2017 when 43 patient advocates from 24 countries gathered with several clinicians at the 2nd MPN Horizons International Conference for MPN Advocates. More reports coming soon.

Here are just a few headlines:

“These diseases will eventually be called by their mutations rather than Essential Thrombocythemia, Polycythemia Vera, and Myelofibrosis.”

~ Martin H. Ellis, MD, Meir Medical Center and Tel Aviv University, Chairman of Israel MPN Working Group

“Patient Reported Outcomes are, in fact, doctor reported outcomes; not actually from the patient. There is work to be done.”

~ Sarunas Narbutus, European Patients Academy on Therapeutic Innovation (EuPATI)

“The aging of hematopoietic stem cells may play a role in the mutations, and the health of the niche where the stem cells reside is also important… There appears to be hierarchy among mutations and competition among them.”

~ Saghi Ghaffari, MD, PhD, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai

“When someone receives a MPN diagnosis, their cognitive map lights up based on beliefs, knowledge, expectations, psycho-emotional reactions, and personality traits.”

~ Ketti Mazzocco, PhD University of Milan, Department of Oncology and Hemato-oncology; European Institute of Oncology



My Child is Being Evaluated for an MPN

How to Approach the Conversation with Your Child’s Hematologist

Dr. Nicole Kucin, MD, MS Assistant Professor of Pediatrics, Pediatric Hematology/Oncology, New York Presbyterian Hospital/Weill Cornell Medicine.

By Nicole Kucine, MD, MS
It can be difficult to know what to expect when your child is being evaluated for an MPN. There is limited guidance on the internet, which can make specialist visits overwhelming to families. As parents, you can expect that you and your child will be asked many questions about symptoms he or she might be having, including headache, abdominal symptoms, rashes, and itching. Your child will undergo a number of blood tests, including some genetic tests, as well as a bone marrow examination. Children who are having symptoms specific to a certain body area may need radiologic tests (such as an ultrasound or MRI.) You should feel free to ask anything you want, and make sure if you are searching the internet you look at reliable sources (such as the MPN Research Foundation, MPN Advocacy Education International, or Some of the questions I am often asked include the following:

Does my child have cancer?
This is a tricky question, and others may disagree, but I do not think of children with MPN as having cancer. In adults, the World Health Organization criteria considers MPN to be chronic forms of leukemia. We are still evaluating MPN in children, and at this point it is not clear that they are all the same disorders in kids as they are in adults. I view the classical MPN in children as chronic bone marrow disorders, and while they have the potential to transform to acute leukemia, this is not something that has been reported in the literature. By envisioning these as chronic illnesses, I think it helps to set the expectations for long-term follow-up and aiming for keeping day to day activities as normal for your child as possible.

Does my child need the bone marrow evaluation?
The answer to this is definitely yes. The bone marrow exam is an extremely important part of the diagnostic process. It can provide a lot of information about what is going on with your child’s blood cells at the source. Things like storage iron, fibrosis, and the appearance of the precursor blood cells are studied. The procedure itself is performed with anesthesia to make sure your child is asleep during the bone marrow test and doesn’t remember it. The pain following a bone marrow test is generally very mild, and children may not require any pain medicine or might require a dose of Tylenol.

What type of MPN does my child have?
The diagnostic criteria for the various types of MPN are based on years of study and data on adult patients. They include features like appearance of bone marrow cells, genetic findings, and lab criteria. Making the appropriate classification for adult patients is important for discussions of prognosis and treatment. We do not yet know if we can directly apply these criteria to children, and knowing the exact type of MPN each child has may not be possible. While it is important to gather all of this information in children, it may not be as important to specifically name the exact type of MPN, and “MPN, unclassifiable” is an appropriate diagnosis for a number of children. The decisions about how to counsel families, what treatments may be recommended, and what follow-up is needed, will be made based on a variety of findings.

Does my child require treatment for his or her MPN?
The answer to this question varies, as I do not believe treatment is required for all children with MPN. I usually determine the need for treatment based on an individual child’s symptoms and lab findings. I generally do not recommend treatment for children who are asymptomatic and have reassuring labs. Children with mild symptoms in the setting of a high platelet count can often benefit from low-dose aspirin, as long as they are not showing evidence of bleeding or acquired vonWillebrand disease. Children with high red blood cell counts can also benefit from low-dose aspirin or phlebotomy. When a child has a severe clinical event such as a blood clot, or does not have improvement of symptoms with initial therapy, then cytoreductive therapy is appropriate. Which medication is used should be decided based on a conversation with the family and the treating doctor. I have been asked about what is my “cutoff” for high platelet or red cell counts for treatment, and there isn’t a standard cutoff. For example, I don’t think an asymptomatic child with a platelet count of 1.3 million necessitates treatment if they are feeling well and otherwise healthy. If you asked 10 different hematologists, you would probably get 10 different opinions on when to treat, so I think it’s important to have a conversation with your hematologist about the risks and benefits of different treatments.

While it can be frustrating to be facing a rare disease, there is ongoing research to help us better understand these conditions in children and adolescents. Keeping an open mind and making sure you have good communication with your child’s hematologist is the most important thing you can do.

MPN Advocacy and Education International Attends a Workshop Hosted by the FDA

By Ann Brazeau, CEO MPN Advocacy & Education International

MPN Advocacy & Education International was invited to attend a very important and timely meeting with the FDA last month. The invitation was extended to us and a few other MPN focused organizations. This meeting launched a unique beginning for those of us representing the MPN Community.

The FDA’s newly formed Oncology Center of Excellence and the Office of Patient Outcomes are committed to engaging MPN patients and advocates to better respond to the need for quality treatment options.

Among the many topics presented by their hematologists, researchers and cancer patient liaison, was an in depth explanation on drug approval processes and how valuable and critical the patient’s voice is to their mission.

After a drug is approved, companies are required to send frequent updates on any and all reported adverse side effects from their drug. Physicians also report on these events and patients can do so by contacting the FDA directly through Med Watch Consumer Voluntary Reporting. Go to Patient Reported Outcomes are extremely important and valuable to the Drug Approval Process and after a drug is approved.

We also learned the complexities surrounding drug “holds” and what happens and why when that hold begins and when it is released. They stressed the importance of ongoing communication between BioPharma and the FDA and encourage regular conversations and frequent updates with comprehensive data.

As the MPN Community pursues the use of Interferon and hopes for accessibility to Interferon as a viable option for treatment, we learned that company(ies) producing Interferon would have to apply for approval specifically for MPNs. It could be a daunting process but there may be avenues we can utilize through patient advocacy efforts.

Although we did not share all of our concerns at this meeting, we look forward to subsequent meetings where we hope to tackle the issues of endpoints, pricing, fast-tracking, and other challenges surrounding MPN drug approval. We were very pleased to have had this opportunity.





Hematopoietic Cell Transplantation for Myelofibrosis

Primary myelofibrosis is a bone marrow disorder caused by clonal proliferation of stem cells. There are several treatment options available for treatment including recent introduction of JAK2 Inhibitors. Allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for these patients.

Guest post by Dr. Haris Ali and Dr. David Snyder, City of Hope

Application of HCT for treatment of myelofibrosis was delayed in part due to concern for engraftment failure from fibrotic marrow, and due to the older age of most patients.  After initial studies showed that successful engraftment can be achieved its use has been consistently increasing 1,7,8,10.

Types of Allogeneic Transplant:

A. Depending on donor type:

  1. Matched sibling donor. Better outcomes post HCT among all donor types. They account for about 30-35% of donors.
  2. Matched Unrelated donor. Per several studies the outcomes of transplants using either related donors or well HLA matched unrelated donors are similar.
  3. There are no published data about using cord blood and haploidentical donors for transplant in this setting.

B. Conditioning regimen:

Prior to transplant patients receive treatment called the conditioning regimen which includes chemotherapy with or without radiation. The purpose of conditioning is twofold, one to reduce disease burden and second to suppress recipient’s immune system to allow engraftment of stem cells.

  1. Myeloablative Conditioning (MAC):
    MAC involves administration of fractionated total body irradiation (FTBI) and/or alkylating agents at high doses after which the chances of autologous recovery are minimal. It is associated with significant morbidity. It is thus generally limited to younger patients with good performance status.  The most commonly used regimens included targeted Busulfan /Cyclophosphamide and fractionated total body irradiation (TBI) based regimens.
  2. Reduced intensity Conditioning (RIC):
    RIC involves administration of radiation and/or alkylating agents at about 30% intensity. Examples of this type of regimen include Fludarabine/melphalan or fludarabine/Busulfan. They are associated with much less morbidity and lower rates of non-relapse  mortality (NRM). Such regimens can be utilized in older patients or in those with co-morbidities who would otherwise not be candidates for HCT.

Who to consider for HCT:

There is considerable heterogeneity in terms of progression and survival of patients with myelofibrosis. The transplant process itself is associated with some risk of morbidity and mortality. This risk has improved considerably with improve supportive care, introduction of RIC and also better understanding of radiation and chemotherapeutic agents (e.g targeted Busulfan) 7. Patients at greater risk of progression and shortened survival are thus considered for HCT. There are several scoring systems available to predict prognosis including IPSS, DIPSS, and DIPSS Plus. Recently DIPSS has been shown to predict outcome after HCT 7.

HCT is recommended for all suitable patients with intermediate 2 or high risk disease. Lower risk patients with transfusion dependency, thrombocytopenia and adverse cytogenetics may be considered due to their higher risk of progression. Figure 2 shows survival of various risk groups post transplant.

Figure 2: OS by DIPSS category (footnote 7)

Figure 2: OS by DIPSS category (footnote 7)

Additional risk factors that may affect transplant outcomes:

  1. Size of spleen
  2. History of splenectomy pre and post HCT
  3. JAK2  mutation and prior use of JAK2 inhibitors
  4. Portal hypertension

Outcomes of HCT for Myelofibrosis:

Myeloablative Conditioning:

Initial studies of HCT in myelofibrosis mainly included MAC regimens. Guardiola reported in 1999, 55 patients receiving mainly TBI based or Busulfan based MAC. The 5 yr survival was 47%, 1 yr NRM was 27%. Deeg reported in 2003 Fred Hutchinson experience with MAC. 44 patients received Bu/Cy and 12 patient received TBI based regimens.  3 yr survival was reported as 58% with 32% 1 yr NRM.

Reduced Intensity Conditioning:

MAC is not an option for most of the patients with myelofibrosis due to advance age at diagnosis and co- morbidities. Thus RIC is considered an attractive alternative for these patients. This approach relies on graft versus tumor effect as the main modality to treat myelofibrosis. This effect is an immunologic reaction of the donor’s T lymphocytes against the neoplastic myeloproliferative stem cells. Kroger et al. reported outcomes of 103 patients with median age of 53 yrs. 1 yr NRM was only 6% with 5 yr overall survival of 67% and progression free survival  of 51%. Similar outcomes have been reported by other groups. The City of Hope experience of 71 pts treated with allogeneic HCT from 2007-2012 showed OS of 73%. The most common conditioning regimen used was fludarabine/melphalan with tacrolimus and sirolimus for GVHD prophylaxis.

Complications associated with transplant.

  1. Graft versus host disease (GVHD):
    Despite prophylaxis GVHD is a common complication of allogeneic HCT. It is characterized by immune responses from donor immune cells against recipient antigens causing organ dysfunction. Risk factors are as follows:

    1. Related vs. unrelated donor
    2.  Degree of HLA match (10/10 vs 8-9/10)
    3. Gender disparity (more in  female donor and male recipient)
    4. Source of stem cells, peripheral blood  vs. marrow
    5. Conditioning

    It is classically divided into 2 types depending on the onset from time of transplant.  Acute GVHD occurs within 100 days of transplant and chronic GVHD occurs generally after 100 days of transplant. It is now known that there is a considerable overlap in terms of onset and manifestations. There are staging and grading systems developed to determine severity of GVHD.  Acute GVHD usually affects 3 organ systems: skin, liver, and gastrointestinal tract. Reported incidence of GVHD is anywhere between 20-80% depending on risk factors. The incidence of Grade 3 to 4 GVHD is about 10-20%. Recent report from Scott et al. reported overall incidence of about 68% with grade  3 or 4  GVHD of 18%.

  2. Non Relapse Morality:
    This includes all deaths without prior progression. The risk of NRM is much higher with conventional MAC with 1year NRM of about 25-45% whereas for RIC it is 10-16%.
  3. Relapse:
    Relapses are usually seen in the setting of graft failure and autologous recovery. Earlier studies showed 5 yr probability of treatment failure up to 36% 6. They found that older age, cytogenetic abnormalities, and absence of GVHD were associated with treatment failure. More recent studies have reported relapse rates of about 11% 7.
  4. Graft Failure:
    Reported incidence of graft failure differs in the literature. Initial studies reported relatively high rates of graft failure. In a large CIBMTR study Ballen et al. reported an incidence of 9% in matched siblings compared to 20% in unrelated donors 9. More recently Scott et al. reported rates of graft failure of <10%. They did not find any association of degree of fibrosis, prior splenectomy, or conditioning regimen with graft failure.


  1. O’Donnell MR, Nademanee AP, Snyder DS, et al. Bone marrow transplantation for myelodysplastic and myeloproliferative syndromes. J Clin Oncol 5:1822, 1987
  2. Tefferi A. How I treat myelofibrosis. Blood. 2011; 117(13):3494-3504.
  3. Snyder DS, Palmer J, Stein AS, et al. Allogeneic hematopoietic cell transplantation following reduced intensity conditioning for treatment of myelofibrosis. Biol Blood Marrow Transplant 2006;12:1161-8.
  4. Deeg HJ, Gooley TA, Flowers ME, et al. Allogeneic hematopoietic stem cell transplantation for myelofibrosis. Blood. 2003;102(12):3912-3918.
  5. Bacigalupo A. Ballen K. Defining the intensity of Conditioning Regimens: Working Definition. BBMT 2009 1628-1633
  6. Passamonti F, Cervantes F, Vannucchi AM, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for myeloproliferative Neoplasms Research and Treatment). Blood. 2010;115(9):1703-1708.
  7. Guardiola P, Anderson JE, Bandini G, et al. Allogeneic stem cell transplantation for agnogenic myeloid metaplasia: a European Group for Blood and Marrow Transplantation, Societe Francaise de Greffe de Moelle, Gruppo Italiano per il Trapianto del Midollo Osseo, and Fred Hutchinson Cancer Research Center Collaborative Study. Blood. 1999;93(9):2831-2838.
  8. Scott et al. The Dynamic International Prognostic Scoring System for Myelofibrosis predicts outcomes after hematopoietic cell transplantation. Blood 2012; 119: 2657-2664
  9. Deeg HJ, Appelbaum FR. Indications for and current results with allogeneic hematopoietic cell transplantation in patients with myelofibrosis. Blood. 2011;117(26):7185.
  10. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant. 2010;16(3):358-367.

Photo credit: Flickr, cbucky

New Prescribing Information for Jakafi

Incyte Corporation announced today that the U.S. Food and Drug Administration (FDA) has updated prescribing information for Jakafi® (ruxolitinib) to include new recommended dosing guidance for patients with low platelet counts and additional safety information. Approved in November 2011, Jakafi is the first and only FDA-approved product for the treatment of patients with intermediate or high-risk myelofibrosis.

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Incyte’s Management Presents at Global Healthcare Conference

Dr. Reid Huber, Senior VP of Discovery Biology and David Hastings, Chief Financial Officer of Incyte Corporation presented at a global healthcare conference sponsored by Goldman Sachs. Navdeep Singh, a biotech analyst with Goldman Sachs, moderated the conversation.

Excerpt: “The idea behind Jakafi really began in the 2003-2004 timeframe when it was realized that JAK’s at activation was fundamental to many oncology situations as well as chronic inflammatory diseases, and while there was an inhibitor out there, tofacitinib, a pan-JAK inhibitor at that time in development for transplant. The team at Incyte saw a tremendous opportunity for a more selective JAK1/JAK2 inhibitor across a range of diseases in unmet needs. And it was true some terrific execution on the chemistry and the biology side, fantastic execution in drug development to bring a molecule to market and an indication without any approved therapy, without any known regulatory path and really bring the first therapy to patients with Myelofibrosis, but again getting back to the genesis of that effort and that was kind of an acceleration strategy for us.” – Dr. Reid Huber

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Canada Trails Internationally in Access to Orphan Drugs

This weekend, Canadians with Pompe Disease and their caregivers will gather in Toronto for their annual conference to share experiences and hear about new developments aimed at addressing Pompe Disease as well as Orphan Drug accessibility in Canada. Orphan drugs are pharmaceuticals that have been developed specifically to treat very rare medical conditions like Pompe disease. These diseases are often referred to as orphan diseases.

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Long-Term Jakafi Treatment May Stabilize or Reverse Bone Marrow Fibrosis

Incyte Corporation announced that results from an exploratory analysis of bone marrow fibrosis data from an ongoing Phase I/II single-arm, open-label clinical trial for Jakafi® (ruxolitinib) were presented today at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Fibrosis of the bone marrow, a cardinal feature of myelofibrosis (MF), was shown to stabilize or reverse after 24 and 48 months of Jakafi treatment in the majority of patients with MF, a magnitude of an effect not seen with long-term treatment with hydroxyurea. Jakafi, an oral JAK1 and JAK2 inhibitor, is FDA-approved for the treatment of patients with intermediate or high-risk myelofibrosis.

“These results provide the first evidence of a drug therapy that may stabilize or improve bone marrow fibrosis and are encouraging because the only other proven option is bone marrow transplantation, which is a procedure with high risks. Future studies should improve our understanding of the significance of these findings,” stated presenting author Hans Michael Kvasnicka, M.D., of the University of Frankfurt in Germany. According to Kvasnicka, additional research, including a European LeukemiaNet international initiative, is ongoing to better define the role of fibrosis in MF.

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