From Cleveland to Pittsburgh: A Busy Travel Schedule Worth Every Minute

Pittsburgh

Top left, Dr. James Rossetti, Pittsburgh Support Group Coordinator, Jean Diesch, with Ann Brazeau, Dr. Salman Fazal with Dr. John Mascarenhas and Dr. Raajit Rampal.

On June 7, MPN Advocacy & Education International held its first MPN Patient/Caregiver program in Pittsburgh. Support Group Coordinator, Jean Diesch, invited us many times and we were finally able to make it happen. Two local hematologists, Drs. Fazal and Rossetti joined Drs. Rampal and Mascarenhas for this program.

Dr. Rampal, Memorial Sloan Kettering, presented on new therapies in MPNs, The good news is the development of new JAK inhibitor therapies on the horizon for MPN patients. Click here to view new clinical trials.

Dr. John Mascarenhas, Mount Sinai, discussed new polycythemia vera therapies. Comparing the goals of PV patients to feel better, and the goal of investigators to take what they are doing in the lab and bring it to the patient. Dr. Mascarenhas believes clinical trial participation is the pathway to a cure. This resulted in an excellent discussion with the patients on what they can do to help. Dr. Mascarenhas urged patients to consider donating to a tissue bank. Mount Sinai has a donation program in place, click here to learn more.

Dr. James Rossetti, UPMC Hillman Cancer Center, gave an overview of bone marrow biopsies and aspirations, including how they are done, what is extracted and why, and what they can learn. Many patients have multiple biopsies over the course of their disease.  Biopsies are helpful in creating a baseline for assessing the progression of the disease. (There is a new method being researched to produce non-invasive biopsies, click here to learn more.)

Dr. Salman Fazal, Temple University School of Medicine, reviewed the findings from the MPN Landmark Study. This study highlighted the differences in treatment goals and perception of symptom burden between patients and the hematologists/oncologists who treat MPN patients. While patients listed slowing the progression of the disease as their top priority, physicians listed the reduction in symptom burden, thrombotic events, as their primary goal. For many physicians, this offered unique insights into a patient’s mindset. To learn more about the outcomes of this study click here.

From Cleveland to Pittsburgh: A Busy Travel Schedule Worth Every Minute

Cleveland

MPN Advocacy and Education International hosted its 3rd MPN Patient/Caregiver program at the Cleveland Clinic on May 31. Dr. Aaron Gerds presented information on two MPN topics, Symptom Burden and MPNs 101.

Dr. Gerds helped explain the biology of MPNs and likened the JAK2 mutation to a broken thermostat. In this case, constantly triggering the body to turn up the heat (see slide). His discussion on symptom burden provided a keen insight into why patients endure extreme fatigue, itching and other constitutional issues. Dr. Gerds recommended reviewing the yoga study. The majority of patients who participated found some level of relief and improvements in their quality of life. (read more about the yoga study)

 

Dr. Betty Hamilton, Cleveland Clinic, presented on bone marrow transplants for MPN patients and how to determine the optimal time to proceed. Are the current treatments reducing the symptom burden? Is the patient healthy enough to recover? It is a matter of finding that point at which it will maximize survival and improve the patient’s quality of life. It isn’t age as much as the overall fitness of the patient. One of the most common issues for patient’s recovering from transplant is graft vs host disease, which affects more than half of transplant patients.

Dr. Kristen Pettit, University of Michigan, gave an overview of clinical trials and the benefits of participation. Patients who participate receive quality care from MPN experts.  The protocols in place are designed to ensure the utmost safety of the patient. Participating in a clinical trial is a big commitment. Patients should be aware of all the necessary requirement.

Click here for a list of questions to consider before participating in a trial

Click here for a list of current mpn clinical trials

 

Dr. Naveen Pemmaraju, MD Anderson, discussed what is on the horizon for MPN patients. He encouraged physicians to pay attention to what patient’s are dealing with beyond the visible symptoms. “No one understands the war going on inside your body.” MD Anderson is currently working on several clinical trials for MF patients:

Evaluation of Ruxolitinib in Combination With PU-H71 for Treatment of Myelofibrosis.

Testing of SL-401 in Advanced, High Risk MPN Patients

 

From left, Dr. Aaron Gerds, Dr. Naveen Pemmaraju, Dr. Kristen Pettit and Dr. Betty Hamilton

Structure of protein pair provides blueprint for future drugs

Walter and Eliza Hall Institute researchers have visualised for the first time how the protein SOCS1 ‘switches off’ cell signalling to dampen immune responses and block cancer growth.

The atomic-level structure of SOCS1 binding to its partner protein JAK could guide the development of drugs that alter disease-causing cell signalling pathways, and may have applications for treating some blood cancers, including leukaemias.

The research, led by Dr Nick Liau, Dr Nadia Kershaw, Associate Professor Jeff Babon and Professor Nick Nicola, was published in the journal Nature Communications.

AT A GLANCE

– The SOCS1 protein binds to JAK proteins to ‘switch off’ cell signalling, which dampens processes including immune responses and cancer growth.

– Our researchers have used structural biology to visualise how SOCS1 binds to JAK proteins in never-before seen detail.

– The detailed structure may guide the development of new drugs that modify JAK activity, amplifying or dampening cell responses, with potential applications in cancer therapies.

Learn more about clinical trials

 

Read more

New Data Proves Role of Thrombosis in Patients with MPNs

New research published in Annals of Internal Medicine shows that the rate of arterial and venous thrombosis was significant in patients with myeloproliferative neoplasms (MPNs).

MPNs include a variety of blood disorders, like myelofibrosis, polycythemia vera, and essential thrombocytosis, and patients with them have been reported to be at increased risk for thrombotic events. Pharmacologic treatment can stabilize the blood counts, but they generally provide only partial symptom improvement. Until recently, no population-based study has estimated the excess risk with matched control participants.

Malin Hultcrantz, M.D., PhD and colleagues, in an effort to address the gap in knowledge, evaluated data from 9,429 patients – 46% of whom were male – diagnosed with MPNs who reported to the Swedish Cancer Register between 1987 and 2009, and matched them to 35,820 control participants and compared their rates of arterial and venous thrombosis. Median age of study participants was 72 years, and a mong them, 3,001 had polycythemia vera, 3,462 had essential thrombocythemia, 1,488 had PMF, and 1,478 had MPN unclassifiable.

Read more

ASH: Pegylated Interferon Alfa-2a Active in Hydroxyurea-Resistant PV and ET

Treatment with pegylated interferon alfa-2a led to objective responses in about two-thirds of patients with hydroxyurea (Hydrea)-resistant/intolerant polycythemia vera (PV) or high-risk essential thrombocytopenia (ET), a phase II study of salvage therapy showed.

At 12 months, 69% of patients with ET and 60% of those with PV had achieved objective responses. The overall response rates (ORR) included complete responses (CRs) in 43% of the ET group and in 22% of the PV group.

No new safety or toxicity signals emerged from the MPD-RC 111 study, Abdulraheem Yacoub, MD, an associate professor of medicine at the University of Kansas Medical Center, reported at the 2017 ASH Annual Meeting.

Read more

View more clinical trials

 

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.

Watch video

Reappraising the Approach to PV and ET

Description of recurrent genetic abnormalities in driver genes, a better appreciation of the key diagnostic role of bone marrow features, results of large epidemiologic studies, and landmark controlled clinical trials have resulted in a reappraisal of the approach to polycythemia vera and essential thrombocythemia, authors noted in a recent review.

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The MPN Yoga Study: A Patient’s Story

MPN Patient Amy Wang Manning, Portland, Oregon

By Amy Wang Manning

As I typed one day at work this past spring, my left pinkie suddenly didn’t feel right. A moment later, my left thumb curled under; I couldn’t straighten it except by pulling it with my right hand. Then my entire left hand stiffened into a useless claw. And a tingling sensation was spreading rapidly up my left arm and to my shoulder. I told my boss I needed medical attention. Soon I was in a hospital emergency room, undergoing an MRI.
I didn’t have a stroke that March day. But several weeks later, a hematologist oncologist gave me a diagnosis I’d never heard of: essential thrombocytosis (ET), based on the clot I’d experienced, along with a platelet count of over 1 million and a positive test for the JAK2 mutation. He said I’d probably had ET for as long as 20 years. Suddenly, a lot of health symptoms and setbacks that I’d experienced over that time period made sense.
While I researched essential thrombocytosis online, I stumbled across a call for participants in a pilot study at Arizona State University. The researchers wanted to investigate whether patients with essential thrombocytosis and other myeloproliferative neoplasms could find some relief from symptoms such as pain, fatigue and insomnia by using a mobile app for guided meditation.
While I hadn’t experienced much pain, I’d been having bouts of fatigue and I’d struggled for years with insomnia, which seemed to be worsening. I had practiced yoga and found it helpful in managing my emotional, mental and physical health, so meditation seemed appealing. It certainly couldn’t hurt. And the eight-week study wasn’t asking much of participants: Fill out a few questionnaires, keep a daily sleep log, and wear a Fitbit to track my daily activity. I applied to the study and was accepted. The daily meditation sessions turned out to be very reasonable, just 10 minutes a day.
Now that the study’s finished, I feel calmer and more able to handle whatever comes my way with this disease. I continue to meditate with the app I tested. If nothing else, I am now better equipped to take a deep breath, let go of what I cannot control, and just focus on the moment – this moment, in which I am still here, living.

Incyte Announces Pivotal Clinical Trial of Ruxolitinib for Treatment of ET


WILMINGTON, Del.–(BUSINESS WIRE)–Nov. 15, 2017– Incyte Corporation (Nasdaq:INCY) today announced that the first patient has been treated in the RESET pivotal trial evaluating ruxolitinib (Jakafi®) compared to anagrelide for the treatment of patients with essential thrombocythemia (ET) who are resistant to or intolerant of hydroxyurea (HU).

“We are pleased to treat the first patient in our pivotal trial evaluating ruxolitinib as a treatment for ET, a rare blood cancer that can lead to life-threatening complications,” said Steven Stein, M.D., Chief Medical Officer, Incyte. “We look forward to building on the clinical evidence for ruxolitinib and to advancing this trial to help address the needs of higher-risk patients with ET, who are resistant to or intolerant of HU and currently have limited treatment options.”

ET is a rare, chronic blood cancer, part of a group of related blood cancers known as myeloproliferative neoplasms (MPNs), characterized by increased platelet production, a white cell count above the normal range, persistently elevated platelet counts with normal red blood cell mass and the absence of prominent bone marrow fibrosis.1 An increased platelet count can increase the risk of thrombosis. Thrombosis can, in turn, lead to serious health problems including heart attack or stroke. Vascular complications and transformation to myelofibrosis (MF) or acute myeloid leukemia (AML) are the major causes of increased morbidity and mortality in patients with ET.2,3

About the RESET Study

The randomized, double-blind, double-dummy pivotal study (NCT03123588) is evaluating the safety and efficacy of ruxolitinib versus anagrelide as a treatment of patients with ET. The study is expected to enroll approximately 120 patients, 18 years or older, diagnosed with ET who are resistant to or intolerant of HU, with a screening platelet count of >650 × 109/L and white blood cell (WBC) count of >11.0 × 109/L.

The primary endpoint of this study is the proportion of patients who achieve platelet and WBC control over 1 year of follow-up. Key secondary endpoints include safety and tolerability and the proportion of patients who achieve complete remission (CR) or partial remission (PR). For more information about the study, please visit https://clinicaltrials.gov/ct2/show/NCT03123588.

About Jakafi® (ruxolitinib)

Ruxolitinib is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food and Drug Administration, as Jakafi® (ruxolitinib), for treatment of people with polycythemia vera (PV) who have had an inadequate response to or are intolerant of hydroxyurea.

Read more

 

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 cancer.gov.) 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.