Polycythemia Vera: Causes, Symptoms, and Treatment Options [Interview]

Dr_Ellen_Ritchie_Polycythemia_VeraGuest: Dr. Ellen Ritchie and Finola Hughes
Presenter: Neal Howard
Guest Bio: Ellen K. Ritchie, MD is the assistant professor of medicine and a member of the Leukemia Program at the Weill Cornell Medical College of Cornell University and the New York Presbyterian Hospital in New York City. Dr. Ritchie graduated from Barnard College at Columbia University and received her medical degree from the College of Physicians and Surgeons at Columbia University. She completed her internship and residency in internal medicine and her fellowship in hematology and medical oncology at New York Presbyterian Hospital on the Columbia campus.

Segment overview: Segment 1: Rare Disease Day is February 28, and in this segment, Dr. Ellen Ritchie, MD, Associate Professor of Clinical Medicine, Weill Cornell Medical College, talks about a rare chronic and under-recognized blood cancer called polycythemia vera (PV), which is part of a group of rare blood cancers known as myeloproliferative neoplasms (MPNs).

 

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Pacritinib More Effective at Spleen Volume Reduction Than Best Available Therapy in MF

Treatment with the multityrosine kinase inhibitor pacritinib resulted in a significant reduction in spleen volume compared with best available therapy, including ruxolitinib, in patients with myelofibrosis and thrombocytopenia, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting & Exposition.

For the phase 3 PERSIST-2 study (ClinicalTrials.gov identifier: NCT02055781), investigators enrolled 311 patients with primary, postpolycythemia, or postessential thrombocythemia myelofibrosis and platelet counts no greater than 100,000/µL. Participants were randomly assigned to receive pacritinib 200 mg orally twice daily, pacritinib 400 mg orally once daily, or best available therapy, including ruxolitinib.

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MF Patients Needed for Phase 2 Study of INCB050465 in Combination with Ruxolitinib

A Phase 2 Study of the Safety, Tolerability, and Efficacy of INCB050465 in Combination With Ruxolitinib in Subjects With Myelofibrosis

Study Description:   This is a Phase 2 study of the combination of an experimental agent called INCB050465 and the marketed drug ruxolitinib in patients who have myelofibrosis.    The primary purpose of this study is to evaluate the safety and tolerability of INCB050465 in combination with ruxolitinib in patients who have been taking ruxolitinib for at least 6 months.   INCB050465 inhibits PI3K‐Delta, a protein involved in growth and survival of certain types of cells.   Ruxolitinib is a very specific inhibitor of enzymes called JAK 1 and JAK 2, which are important for red and white cell development, and are overactive in people with myelofibrosis.  Ruxolitinib has been approved by the FDA to treat patients with myelofibrosis.  Some patients still have symptoms of myelofibrosis even while being treated with ruxolitinib; the present study will ask the question if adding on INCB050465 provides added benefit for such patients. To be considered for this study, patients must have been receiving ruxolitinib for at least 6 months, with a stable dose for the 8 weeks prior to starting the new therapy.  Patients will either have a spleen that is palpable below their ribs, or have symptoms of myelofibrosis.    Woman cannot be pregnant or breastfeeding or plan to become pregnant.  Several laboratory criteria will also need to be met to qualify for the study.

To obtain further study eligibility details and locate a clinical research site that is participating in thisstudy, please contact us or review the additional study information on clinicaltrials.gov (study identifier: NCT02718300) by clicking here.

MPN Patients Needed for Mayo Clinic Nutrition Survey

Greetings to our myeloproliferative neoplasm (MPN) patients and dear friends!

We would like to tell you a little about one of our new research projects and invite you to participate.  Patients with types of MPNs including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) such as you often experience severe symptom burden including fatigue, abdominal complaints, nausea, weight loss, and constipation. Growing evidence indicates that there are alternatives to traditional pharmacologic therapy that may help to improve these symptoms. To date no research endeavors have investigated the impact that different foods may have in MPN patients.

This research project, entitled the NUTRIENT Trial (NUTRitional Intervention among myEloproliferativeNeoplasms Trial), is designed to evaluate how changes in nutrition can help control MPN disease-related symptom burden. In this first part of our study, we have created a survey to help us understand the dietary needs, habits, and preferences of individuals with MPNs. The link to the survey can be found at:

https://src.co1.qualtrics.com/SE/?SID=SV_6fiTZskivSRXjrT

We ask that you consider partnering with us to improve our understanding of nutrition in individuals with MPNs by completing this survey. We ultimately plan to use this information to develop a nutritional intervention to see if we can change how you feel.

This survey will take an average of 10-15 minutes to complete, although some people make take longer. We do not ask for any sensitive or personal information in this survey, but we do ask about features associated with your MPN disease, what symptoms you are experiencing, your dietary habits and preferences, what supplements you may use, and what dietary needs may not be met (such as weight loss).

We thank you for your time and commitment to improving the lives of MPN patients around the world.

Robyn Scherber MD, Angela Fleischman, MD,PhD & Ruben Mesa, MD

 

 

Blog: A Laugh a Day Keeps the Pain at Bay

In the interest of full disclosure, I am a humor hobbyist. I enjoy finding the funny side of life’s experiences. Wikipedia defines humor (or humour in British English) as “the tendency of particular cognitive experiences to provoke laughter and provide amusement.”

yoga

It may be a form of operant conditioning (yes, like animal training) that hard-wired my brain. I have four younger siblings plus two phantom siblings, “I Dunno” and “NotMe.”   When something broke, went missing, or otherwise upset our parents, the responsible child was usually Not Me or I Dunno. If we could get mom or dad to crack a smile, we wouldn’t be grounded for life. We learned that laughter dissipates anger. It is impossible to sustain the anger emotion while laughing; it flips a switch in the brain.

Coping Skills: Humor and Laughter

Seeking humor also elevates one’s thinking to an observer level, a space once removed from the participant level. This helps to de-personalize the experience and allows time to respond, rather than react, to a perceived threat.

Humor is also a safe way to express fears. When I awoke in the ICU and saw my minister at the foot of my bed talking to my husband, I asked, “Am I dying?” When he said, “I don’t think so.” I replied, “Good. Then I’m happy to see you!”

On more than one occasion during my stem cell transplant journey, I asked various billing departments if they offered discounts for Costco or AAA members. I asked friends and family to help me keep my laugh on by sending funny messages.

Humor does not change the facts of my situation. It helps adjust my perspective, albeit temporarily, to boost my endorphins and find a glimmer of hope to grab.

Serious times call for serious laughter

In the face of uncertainty, a natural reaction is self-protection. Anything that reduces the feeling of vulnerability or fosters a sense of control is fair game. Prolonged stress takes a harmful toll on one’s physical, mental, and emotional health. These conditions can cause one to become laugh-resistant.

A prescription for Humor should be given to everyone living with a chronic illness. Humor, and its powerful side effect, Laughter, contribute to our physical and emotional well-being.

Laughter has proven physical benefits to the human body:

  • Reduces pain (by producing hormones called endorphins in response to laughter).
  • Strengthens immune function. A good belly laugh increases production of T-cells, interferon and immune proteins called globulins.
  • Decreases stress. When under stress, we produce a hormone called cortisol. Laughter significantly lowers cortisol levels and returns the body to a more relaxed state.
  • Exercises organs.  The lungs, heart, abdominal muscles, thorax, liver, diaphragm, and lachrymal glands all are exercised.  Digestive organs are also stimulated.

How to Dose Up Humor and Laughter

Begin where you are.

  1. If a hearty belly laugh seems as likely as running a marathon, begin with a smile. (That is when the ends of your lips curve upwards.) You can show your teeth or keep them covered. Smiles, like yawns and laughs, are contagious.
  1. Count your blessings. Make a list or count on your fingers and toes. Simply focusing on the good things in your life will break the concentration on negative thoughts and feelings. This helps refocus the brain and gives your body a break from stressful thinking.
  1. Listen, Watch, Read funny material. You-Tube has all kinds of humor – funny babies, funny animals, you name it. Remember Lucille Ball, Carol Burnett, and the Three Stooges? Turn off the news channels and surround yourself with kindness and humor.
  1. Look for laughter and smiley people. Seek out people who can laugh at themselves and everyday events. Look for humor in your daily activities. Ask people what’s the funniest thing that happened to you this week?

Exercise EVERYone Can Do: Laughter Yoga

You don’t need a yoga mat and there are no awkward poses with Laughter Yoga. The focus is on deep breathing and full belly laughter. Learn to laugh without humor. It is a body-mind approach that does not require jokes or even a sense of humor. Our bodies and minds cannot discern the difference between laughter triggered by humor or this exercise. Within 90 seconds to two minutes, the laughter becomes real. It is also contagious. Check out http://www.wikihow.com/Do-Laughter-Yoga and Laughter Yoga University to learn more.

 

 

 

 

 

Statement from ASH, AACR, AACI, ASTRO, ASPHO and LUNGevity on Immigration Executive Order

Published on: February 01, 2017

(WASHINGTON, February 1, 2017) — As the world’s leading organizations representing laboratory researchers, physician-scientists, clinicians, the nation’s cancer centers, and patient advocates committed to improved care for patients with cancer and blood diseases, we express our deep concern about the Administration’s executive order that has denied U.S. entry to people who bring unique expertise to the practice of medicine and the conduct of cancer and biomedical research. Our nation depends on the contributions of the greatest minds from around the world to maintain the high quality of our biomedical research enterprise and health care services.

The benefits of scientific collaborations are amplified by our diversity. Limiting the exchange of ideas, practices, and data across cultures has the potential to significantly retard scientific progress and adversely affect public health. Any loss of researchers and physicians will render the United States less competitive over time, and our traditionally strong research institutions and the patients they serve will be negatively affected.

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An Accurate, Simple Prognostic Model for MF Patients

An Accurate, Simple Prognostic Model Consisting Of Age, JAK2, CALR, And MPL Mutation Status For Patients With Primary Myelofibrosis

Abstract

In most patients with primary myelofibrosis, one of three mutually exclusive somatic mutations is detected. In approximately 60% of patients, the Janus kinase 2 gene is mutated, in 20%, the calreticulin gene is mutated, and in 5%, the myeloproliferative leukemia virus gene is mutated. Although patients with mutated calreticulin or myeloproliferative leukemia genes have a favorable outcome, and those with none of these mutations have an unfavorable outcome, prognostication based on mutation status is challenging due to the heterogeneous survival of patients with mutated Janus kinase 2. To develop a prognostic model based on mutation status, we screened primary myelofibrosis patients seen at the MD Anderson Cancer Center, Houston, USA, between 2000 and 2013 for the presence of Janus kinase 2, calreticulin, and myeloproliferative leukemia mutations. Of 344 primary myelofibrosis patients, Janus kinase 2V617F was detected in 226 (66%), calreticulin mutation in 43 (12%), and myeloproliferative leukemia mutation in 16 (5%); 59 patients (17%) were triple-negatives. A 50% cut-off dichotomized Janus kinase 2-mutated patients into those with high Janus kinase 2V617F allele burden and favorable survival and those with low Janus kinase 2V617F allele burden and unfavorable survival. Patients with a favorable mutation status (high Janus kinase 2V617F allele burden/myeloproliferative leukemia/calreticulin mutation) and aged 65 years or under had a median survival of 126 months. Patients with one risk factor (low Janus kinase 2V617F allele burden/triple-negative or age >65 years) had an intermediate survival duration, and patients aged over 65 years with an adverse mutation status (low Janus kinase 2V617Fallele burden or triple-negative) had a median survival of only 35 months. Our simple and easily applied age- and mutation status-based scoring system accurately predicted the survival of patients with primary myelofibrosis.

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Resolution of Thrombocytopenia, but not Polycythemia after Ruxolitinib

Resolution of thrombocytopenia, but not polycythemia after ruxolitinib for polycythemia vera with detectable mutation in the exon 12 of the JAK2 gene

To the Editor

Data on safety and efficacy of ruxolitinib treatment in myeloproliferative neoplasms (MPN) with concomitant thrombocytopenia are scarce and limited to patients with myelofibrosis (MF). It was demonstrated that 11–16% of MF patients had platelet (PLT) count <50 × 109/l at diagnosis and the rate of thrombocytopenia increases with disease progression. Thrombocytopenia in MF may be due to ineffective megakaryocytopoiesis as a result of bone marrow fibrosis or results from platelet sequestration and destruction in enlarged spleen [1]. Immune dysregulation with the production of immune complexes or antiplatelet antibodies may account for low platelet count in single cases [2]. It is noteworthy that thrombocytopenia remains an exceptional finding in polycythemia vera (PV).

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Celgene Is Advancing Research in Myeloid Disease Segment

Myeloid disease segment

In addition to luspatercept and enasidenib, Celgene (CELG) is also exploring other investigational drugs such as sotatercept and CC-486 (oral azacitidine) to treat patients suffering with various myeloid diseases. On December 5, 2016, Celgene and Acceleron Pharma announced preliminary data from an ongoing Phase 2 trial that’s researching the use of sotatercept in patients suffering with myelofibrosis. The trial enrolled 19 patients, and 14 of them received at least five doses of sotatercept. About 36.0% of the 14 patients demonstrated an anemia response, a key endpoint of the trial.

According to Mayo Clinic, “Myelofibrosis is a serious bone marrow disorder that disrupts your body’s normal production of blood cells. The result is extensive scarring in your bone marrow, leading to severe anemia, weakness, fatigue and often an enlarged spleen.”

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Janus kinase-ing’ up the treatment of primary MF: building better combination strategies

Abstract

PURPOSE OF REVIEW:

The article discusses the promising agents that are approved or currently under investigation for the treatment of myelofibrosis and reviews the ongoing Janus kinase (JAK) inhibitors-based combinatorial strategies in this setting.

RECENT FINDINGS:

Myelofibrosis is a Philadelphia-negative myeloproliferative neoplasm with constitutive JAK/STAT activation. The JAK-inhibitor ruxolitinib is the only approved drug for this disease in the United States and Europe based on two randomized phase III studies that demonstrated clinically meaningful reduction in spleen size, improvement in symptoms, quality of life, and an overall survival advantage with prolonged follow-up. Emerging data have revealed the complex molecular architecture of myelofibrosis with clonal evolution playing a central role in disease progression or transformation. These molecular pathways may explain the heterogeneous benefits obtained by JAK-inhibitors in patients with myelofibrosis. In addition, the genetic and epigenetic mutations appear to work in concert with overactive JAK/STAT signaling and contribute to myelofibrosis pathogenesis and prognosis, suggesting a potential to exploit them as potential therapeutic targets.

SUMMARY:

Combining JAK-inhibitors with agents that target parallel prosurvival pathways or agents that enhance hematopoiesis may enhance efficacy and/or mitigate on-target myelosuppression, thereby extending the therapeutic benefits observed with JAK-inhibitors alone.

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