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Interviews with the ExpertsComorbidities: When Other Medical Conditions Affect MDS Treatment

the ConnectionMDS

Fighting Bone Marrow Failure Diseases Through Patient Support and Research Since 1983

David Steensma, MD, FACPDavid Steensma, MD, FACP is an associate professor at Harvard Medical School and faculty member in the leukemia program at Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, Massachusetts. He treats patients with

myelodysplastic syndromes (MDS), leukemia, and other bone marrow failure diseases. His research focuses on clinical trials and new drug development and collaborative efforts related to MDS molecular genetics.

Please explain what comorbidities are and how common comorbidities seen in older MDS patients can affect treatment decisions?

Comorbid conditions or comorbidities are other medical problems besides MDS that can influence both how functional a patient is and also what therapies for MDS can be safely administered. For example, for someone who has advanced kidney failure and is on dialysis, it’s very difficult to know what dose of lenalidomide (Revlimid®) to give them because this drug is eliminated via the kidneys. If the patient has kidney failure, the drug levels might be higher than anticipated.

Other types of organ failure also put patients at increased risk of complications from MDS treatment. For instance, if a patient has emphysema and then gets a pneumonia resulting from the low blood counts that often occur when treatment with azacitidine (Vidaza®) is started, there could be serious complications, and the patient might even die when someone with normal lungs might have survived. In general, comorbid conditions make treating MDS more difficult, worsen the overall prognosis, and can limit the treatment options we have.

Connecting Patients and Families with News and Expert OpinionVoluME 4, NuMbEr 6, NoVEMbEr 2014

Does the degree or severity of a comorbid condition and the type of treatment given affect MDS treatment decisions? It certainly does. To go back to the kidney example – there are patients with very mild kidney dysfunction where the abnormality is not much more than a laboratory test result that is slightly out of the normal range, and this type of mild problem has minimal, if any, consequences for MDS treatment. In fact, in some cases this particular comorbid condition can even help: red cell growth factors like darbepoetin (Aranesp®) or epoetin (Procrit®) can improve hemoglobin levels in MDS, but these drugs are not specifically FDA-approved for MDS and so sometimes Medicare or insurance companies balk at paying for them.

However, these red cell growth factors are approved for people with kidney disease, and they are easier to prescribe in that setting. But there are other patients with severely impaired kidneys or end-stage kidney dysfunction. The way that medication would be cleared by the bodies of those patients would be very different.

The severity of comorbid conditions is also relevant to clinical trials. Most trials of new drugs are trying to enroll a healthier subgroup of patients because if one of the study participants has a bad event while on the trial due to a comorbid condition, it could be erroneously blamed on the drug being studied and lead to problems with that drug’s application with the FDA. For other drugs, the way that they are metabolized is different in patients with comorbid conditions, especially liver or kidney disease.

Connect online with AA&MDSIF and other MDS patients

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Comorbidities t continued from cover

So in many cases, patients with serious comorbidities aren’t eligible to participate in clinical trials. But that restrictive clinical trial eligibility has a downside: it means that when a drug is approved, it has been tested only in patients without comorbid conditions. So if we’re using an approved drug in a patient with a comorbidity, in what is sometimes called the “real world” off-study setting, then we have less of an idea how the treatment will progress since clinical trial results are only partially informative.

Do compound comorbidities necessarily complicate an MDS treatment plan?

Not necessarily; it depends to a large degree on how serious the individual comorbid conditions are and their cumulative effect. In the case of patients with more than one significant comorbidity, it can make patients ineligible for a stem cell transplant or for a clinical trial, and it can make their condition even more difficult to treat with standard therapies such as azacitidine (Vidaza®) or lenalidomide (Revlimid®). The more things that are wrong with a patient, the fewer options there may be. In extreme cases, the prognosis is dictated by the comorbid conditions rather than the MDS.

As an MDS specialist, how do you work with other physicians to coordinate care for patients having other diagnoses, resulting in comorbid conditions?

Communicating with other physicians is a major part of what I do and can sometimes be time-consuming. For example, last month I was attending on a hospital service, and a man from Saudi Arabia flew in by air ambulance and was admitted to my team. He had MDS, but it was the least of his problems, and every day our hematology-oncology health care team spent many hours talking with experts from cardiology, pulmonary disease, infectious disease, intensive care, nephrology, endocrinology, gastroenterology, speech therapy, respiratory therapy, physical therapy, and dietary and nutrition services.

If a patient with MDS needs some kind of elective surgery like a cataract operation, hernia repair, or hip replacement, we try to coordinate that procedure with treatment cycles or with transfusion support in our infusion unit. Or, if it is a non-essential elective procedure, we may delay the procedure until the MDS improves.

Patients with cardiovascular disease or a history of blood clots may be on anticoagulants (blood thinners), and if their platelet count is dropping due to MDS or MDS therapy, they’re at increased risk of bleeding. If that happens, we need to get it touch with the cardiology treatment team and let them know the situation and discuss some medication

changes. So it takes time to coordinate with doctors treating comorbid conditions, but it is absolutely necessary to do the best thing for our patients.

If any comorbid conditions improve through treatment, would that allow MDS treatment to change to a plan previously ruled out?

Potentially, if a comorbid condition improves, the plan could change. For instance, I am currently caring for a patient who was found earlier this year to have a weakened heart, and so the patient was not able to be enrolled in a clinical trial for which he might otherwise have been eligible. But after excellent treatment by a cardiologist, including some medication adjustments, his heart function improved enough to meet the study’s eligibility criteria. He was later able to be enrolled on the trial because the study was still open and had not yet met its enrollment goal. So yes -- if comorbid conditions improve, that can open new doors for patients that previously seemed closed, such as a drug therapy or stem cell transplant.

What is most important for MDS patients and family members to know about comorbidities and MDS?

The doctor and treatment team helping care for the patient with MDS should know about any other medical problems the patients has and what medications and their dosages the patient is taking. This information can influence the overall care and treatment. If a patient with MDS also has serious conditions affecting the heart, lungs, or kidneys, these types of comorbidities will have certainly have an effect on what treatments are available and what the prognosis is. We are starting to recognize this influence on prognosis better than we have in the past and are incorporating tools into the clinic that measure comorbidities as well as MDS-specific characteristics, like chromosome results or marrow blast counts.

Because most MDS patients are older than age 60, many will have other health problems of the sort that often trouble older persons. The bottom line remains that doctors treating MDS must be aware of all other major health conditions patients have and know who the treating physician is for these conditions.

The patient should not be seen just as someone with an isolated disease – as an “MDS patient.” My patients are all people with rich lives outside the clinic and many aspects to who they are—socially and emotionally, as well as physically. Having a full picture of the patient (which of course includes medical comorbidities) will help us deliver the best care to help them enjoy their lives as much as possible.

Interviews with the Experts

Supported by an unrestricted education grant from Celgene Corporation.

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3VoluME 4, NuMbEr 6, NoVEMbEr 2014 • AplAstic AnemiA & mDs internAtionAl FounDAtion

Patient Education Treatment Profilestalking about Blood transfusions

What is a blood tranfusion? A blood transfusion is a safe and common procedure. While some patients might need a blood transfusion because of a loss of blood from an injury or surgery, those with bone marrow failure may need regular transfusions because their bodies can’t make healthy blood cells due to an illness.

Most transfusions usually involve only certain parts of blood. These might be the red blood cells, platelets, or plasma. Rarely is whole blood with all its parts (red cells, plasma, platelets, and white cells) used for a transfusion.

Learn more about blood transfusions for bone marrow failure disease at www.AAMDS.org/Transfusions.

Terms to Know Our online glossary, www.AAMDS.org/Glossary/Terms, helps you understand new words that describe your disease and its diagnosis or treatment. For this edition of the MDS Connection, we define:

Active Treatment Doctors will sometimes refer to certain drugs as “active treatment” or “active drug therapy.” Active treatments are drugs used to treat the underlying cause of the bone marrow failure. These drugs are typically approved by the U.S. Food and Drug Ad-ministration (FDA) to treat a specific disease. It is important to note that active treatments do not cure the disease. For MDS, there are three FDA approved active treatments currently available. These include lenalidomide (Revlimid®), decitabine (Dacogen®), and azacitidine (Vidaza®).

Going Global! Did you know AA&MDSIF now has its MDS patient guide available in French, German, Italian, Portuguese, and Spanish?

Read Your Guide to Understanding MDS

Because patients are looking for answers to the many questions that arise when they are diagnosed with MDS, AA&MDSIF provides expert, reviewed medical information in our comprehensive MDS patient guide.

Watch video interviews with internationally recognized MDS experts discussing:1. What is MDS? 2. How is MDS diagnosed? 3. What is the difference between supportive care

and active treatment for MDS? 4. How are decisions made about the best approach

to treat a patient? 5. What new treatments are on the horizon for

MDS patients?

www.AAMDS.org/GlobalAA&MDSIF is pleased to of-fer Treatment Tracking Tools to help patients monitor their daily symptoms and record their reaction to therapies and treatment progress. This information helps patients see

even small changes in how they feel with treatment.

How it Works Use the Symptom Snapshot section to track and record the day-to-day symptoms and side effects related to your bone marrow failure disease and treatment. The total snapshot score will help you see even small changes over time. You can also track your treatments along with your lab work results so that you can easily see how your treatments affect your overall quality of life.

You can share the information you record on the app or spreadsheets with your doctor or family. The Tracker app is available for smartphones and iPads. It also comes in an Excel spreadsheet version for personal computers, and if you still prefer to use paper and pencil, we have that too! For more information on Treatment Tracking Tools, visit www.AAMDS.org/treatmenttrackers.

Follow Your treatment with treatment tracking tools

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research Research Profile

Eric Padron, MDH. Lee Moffitt Cancer Center & Research Institute

Dr. Eric Padron is a junior investigator, having completed his fellowship in hematology/oncology at the Moffitt Cancer Center in Florida. He describes

his area of interest in bone marrow failure disease as focused on chronic myelomonocytic leukemia (CMML), which is related to myelodysplastic syndromes (MDS).

Although he looks forward to his weekly clinic day when he is able to see patients with MDS, he also notes that the two year fellowship he received through the Edward P. Evans Foundation was invaluable in allowing him to set aside some of his time from other clinical duties, and focus on his research.

In collaboration with his mentors, Drs. Alan List and Rami Komrokji, he has developed an interest in working with existing pharmaceutical compounds to evaluate their effectiveness for bone marrow failure disorders. A trial underway now at Moffitt and other institutions within the MDS Clinical Research Consortium is a study to determine whether the drug ruxolitinib (Jakafi)®, which is currently approved by the FDA for treatment of myelofibrosis, might also work in CMML. Although it’s still early in the research, results with the first few patients look promising.

Other work Dr. Padron is pursuing involves the SRSF2 gene mutation that can occur in MDS and may be related to progression to other diseases. The research underway examines the ability of an existing compound in development to destroy leukemic cells through targeting the cell’s RNA. Positive results from these studies would be a benefit to patients in reducing the symptoms of bone marrow failure diseases, in particular the symptoms that can distress patients, including enlarged spleen, weight loss, and fevers.

Dr. Padron emphasized his appreciation of the funding that made it possible for him to focus on his research and make significant progress early in his career.

He noted that biotechnology research is one of the more expensive activities there is in the medical-scientific community and that funding is essential to the ability to pursue innovative lines of research with potentially significant clinical benefit.

AA&mDsiF Announces new summer Fellowship Grant Program

The Aplastic Anemia & MDS Interna-tional Foundation announces a new program to foster interest among young scientists in exploring a career in bone marrow failure diseases.

The Summer Fellowship Program will offer medical students and graduate students, in the biological sciences, the

opportunity to engage in research under the sponsorship and supervision of an established principal investigator who directs a laboratory dedicated, at least in part, to the investigation of bone marrow failure at a U.S. academic, medical, or research institution.

“A fellow fills an important leadership role in any lab,” says Dr. Lisa Minter, researcher and assistant professor with University of Massachusetts Amherst. “A fellowship can represent an opportunity to grow the field of research in the number of investigators, in diversity of research and in visibility to the greater scientific and medical communities.”

“The AA&MDSIF Summer Fellowship Program will offer students an opportunity to engage in research under the supervision of an established institution. The students will learn valuable skills, gain experience, and develop an interest in the science of bone marrow failure disease,” she added.

Fellowship grants of $5,000 will be awarded to students for a project focused on a bone marrow failure disease. Under the guidance of a mentor who will provide suitable educational and research opportunities, the student will gain valuable experience related to their area of interest.

A generous anonymous donor has funded the first AA&MDSIF fellowship, but more are needed. To support future researchers with a gift or pledge, a gift of stock or through a will or estate gift, contact Teresa Witt, AA&MDSIF major gifts officer at (301) 279-7202 x104.

Summer Fellowship Program applications will be available in December 2014 and accepted January through March 2015. Following review, awards will

be announced in April for a ten-week fellowship for the summer of 2015.

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mDs clinical trialsShould you consider a clinical trial? Ask your doctor or contact the study coordinators for further information. Learn more in the Clinical Trials section of www.AAMDS.org If you are interested in learning more about clinical trials, search for myelodysplastic syndromes studies actively recruiting patients on www.ClinicalTrials.gov. Below is a sampling of the many open studies for MDS patients in the United States.

mDs clinical trials and childrenAccording to the National Heart, Lung and Blood Institute, many medicines given to children have not been studied and approved by the Food and Drug Administration (FDA) for use in children. This is known as “off-label” use. Most of the time, this works well, but because children are not merely little adults, there is a chance that the dose used could be ineffective or even harmful. Without research studies on children with aplastic anemia, the healthcare team may not have the level of information needed to understand the way medicines and other treatments work in a child’s body over time or how those therapies impact a child’s growth and development. The only way to examine the scientific value of a new therapy for children is by conducting a pediatric clinical trial. Should you enroll your child in a clinical trial? Learn more about clinical trials and children by visiting www.AAMDS.org/ChildrenClinicalTrials, then speak with your child’s doctor.

Title Study Purpose Study Coordinator

Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) in Patients With Myelodysplastic Syndromes

The purpose of this study is to see if selinexor will improve the blood counts and bone marrow function in people with your type of MDS.

This study is being conducted at Memorial Sloan Kettering Cancer Center in NY. Contact: Virginia Klimek, MD (212) 639-6519 Please refer to this study by its ClinicalTrials.gov identifier: NCT02228525

A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome (MDS)

The purpose of the study is to test the safety of six cycles of cenersen treatment and to begin to test the hypothesis that intermittent administration of cenersen may lead to a reduced dependence on transfusion.

This study is being conducted at the H. Lee Moffitt Cancer Center & Research Institute, Tampa, FLContact: Jennifer Cooksey, RN Jennifer.Cooksey@moffitt.org Please refer to this study by its ClinicalTrials.gov identifier: NCT02243124

Pilot Study to Assess Hematologic Response in Patients With Acute Myeloid Leukemia or High Risk Myelodysplastic Syndromes Undergoing Monotherapy With Exjade (Deferasirox)

The purpose of this trial is to examine the hematologic response rate of Exjade® in patients with AML and high risk MDS and chronic iron overload from blood transfusions. Deferasirox has been developed as an iron-chelating agent, and unlike deferoxamine, a previously developed iron chelator, deferasirox has the advantage of oral administration.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02233504Contact: James Mangan, MD, PhD(855) 216-0098PennCancerTrials@emergingmed.com

VoluME 4, NuMbEr 6, NoVEMbEr 2014 • AplAstic AnemiA & mDs internAtionAl FounDAtion

research

How are you and your loved ones dealing with the issues related to fighting and living with a bone marrow failure disease? How have you continued to focus on living and enjoying life?

Whether funny or poignant, your story will have meaning and help bring hope to those who see it. You can view samples of stories from other patients by visiting www.AAMDS.org/Hope. Email your story to Mike Breuer breuer@aamds.org. Please include a photograph of your choice in .jpg format.

SHArEyourstorY!

We’d like to find mDs patients and their caregivers who will share their personal experiences with us in a 500-1000 word (1-2 pages) Story of Hope.

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Patient Education communicating with Your medical team – Vital for Best care“A good doctor makes all the difference. I was diagnosed almost two decades ago. My relationship with my doctor and nurse practitioner has been the most important piece for me. Continuous education that is honest and clear opens difficult conversations with compassion.”

– Respondent to AA&MDSIF patient survey

AA&MDSIF has worked with MDS experts to learn more about living with with this rare bone marrow failure disease. By experts, we mean you, our patients. Thanks to all 314 of you who took the time to help us learn more about your understanding of MDS and the factors that lead to your treatment

decisions. And we compared what you said with what medical experts (the doctors) told us.

Results from our 2013 survey reported on disparities in perceptions of disease characteristics and treatment outcomes between physicians and patients (Steensma et al, Cancer 2014) at the time of diagnosis. We learned that when compared to patients, physicians and other healthcare professionals tended to overestimate the benefits of treatment with respect to patients’ quality of life, yet patients were more willing to continue treatment despite side effects if there was a chance of benefit.

In the current study, we further examined gaps in communication between patients and their doctors. We looked at the role of these conversations in treatment discontinuation decisions throughout the disease course. This December, Dr. Aaron Gerds from Cleveland Clinic will present the results of our 2014 MDS Treatment Adherence Survey at the American Society of Hematology meeting in San Francisco, CA.

We’ll share more results in future newsletters, but in the meantime, we want to encourage open communication between patients and their healthcare providers throughout treatment. This is especially important if MDS progresses. Remember, you are all on the same team!

YOU TELL US!AA&MDSIF wants to know– what you would like to know?

Please send a note to AA&MDISF – Tell Us 100 Park Ave., Suite 108, Rockville, MD 20850 or email editor@aamds.org and let us know:1. What topics would you like to see in the 2015 MDS

Connection?

2. What AA&MDSIF programs have you attended or services have you used? How have they helped you?

3. How can we make them better?

4. Is there anything else you would like AA&MDSIF to know–so we can serve you and other MDS patients better?

Don’t Miss our recent MDS Webinars at www.AAMDS.org/learn Bone marrow transplant for mDs and other Bone marrow Failure Diseases: Before, During and After

Speaker: Christopher Cogle, MD

MDS research updates

Speakers: Dr. Timothy Graubert Valeria Santini, MD

Managing Side Effects to Improve Quality of life with Myelodysplastic Syndrome

Speaker: Sara Tinsley, MS, ARNP, AOCN

recent Advances in understanding the Molecular Pathogenesis of Myelodysplastic Syndromes

Speaker: Laura Michaelis, MD, ABIM

understanding Your risk: ipss & ipss-r classification for myelodysplastic syndromes

Speaker: Rami Komrokji, MD

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Awareness

VoluME 4, NuMbEr 6, NoVEMbEr 2014 • AplAstic AnemiA & mDs internAtionAl FounDAtion

You’ve made AA&MDSIF your most trusted source for information about bone marrow failure diseases. Thanks to you, our patient and family conferences, online learning programs, Communities of Hope, and many other important programs and services are provided free of charge.

•You’vehelpedusfundcriticalmedicalresearch.Yourgenerosityis helping to find better treatments and cures through AA&MDSIF research grants.

•You’veexpandedpublicawarenessbyparticipatinginHope,Steps & A Cure Walks and countless other special events.

•You’veenabledmedicalprofessionalstogetthemostup-to-date information about bone marrow failure diseases, their diagnosis, and treatment.

Now picture AA&MDSIF being able to do even more for our patients and their families in 2015. This holiday season, please join usagainandcontributeyourtax-deductibleGiftofHope. Donate today at www.AAMDS.org/Donatenow.

“We see a hopeful future thanks to AA&mDsiF.” – The Rivera Family

AA&mDsiF supports all patients and families living with bone marrow failure diseases through education and awareness.

A strong partnership with you today, tomorrow, and always.

We shAre your vision

social media – transforming the Way We communicate Social media tools help you interact with the entire MDS community–patients, families, healthcare providers, and researchers–in significant ways. These online communication channels also help us reach patients who might not know about our programs and services.

now is the time to get social!

Using social media, you can find information, opinions, and advice from AA&MDSIF, the research and healthcare communities, and other patients. Getting answers can be as simple as following and engaging us on Twitter (www.twitter.com/aamdsif) or starting or joining a conversation with a question or comment on our Facebook page (www.facebook.com/aamds).

You can also visit our YouTube channel (www.youtube.com/aamdsif) for a wide range of relevant video content–top experts discussing the latest in research and treatment, patient testimonials, and more–while also communicating with others who have viewed these same videos.

by the numbers

• Our number of Facebook fans is over 8,000, having more than doubled in a year.

• With over 150 videos, including all that appear on our Online Learning Center (www.AAMDS.org) and more being added each month, our YouTube channel is becoming a comprehensive online video library of topics in MDS-related research and treatment, enhanced by personal experiences and stories.

• With over 600 followers, our Twitter feed is seen and further disseminated by not only patients, but also by numerous research and treatment institutions, professional societies, advocacy and policy groups, and media outlets.

start building your online community now!

So whether you’re a patient, family member, friend, or a healthcare professional, you’ll find and connect with new resources. If you want to know what other MDS patients around the world are thinking, saying, and doing, get social with AA&MDSIF!

facebook.com/aamds

twitter.com/aamdsif

youtube.com/aamdsif

facebook.com/aamds

twitter.com/aamdsif

youtube.com/aamdsif

facebook.com/aamds

twitter.com/aamdsif

youtube.com/aamdsif

facebook.com/aamds

twitter.com/aamdsif

youtube.com/aamdsif

AA&MDSIF wants to know– what you would like to know?

connecting patients and Families with News and Expert opinion

Fighting Bone Marrow Failure Diseases Through Patient Support and Research Since 1983www.AAMDS.org

100 Park Ave., Suite 108 | Rockville, MD 20850

the ConnectionMDS

answerssupport&h pe

Fact sheets• AA&MDSIF Social Media• Bone Marrow and Stem Cell Transplantation** • Clinical Trials**• Communities of Hope• Financial Resources • How to Evaluate Health Information

on the Internet• Iron Overload • Online Learning Center

Patient Guides• Your Guide to Understanding MDS*• Understanding MDS Drug Therapies• Living Well With Bone Marrow Failure Disease**

To order a patient packet, call (301) 279-7202 x116, or order online at www.AAMDS.org/Info.

* Available in French, German, Italian, Portuguese and Spanish ** Available in Spanish

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Phone Support for Personal Attention Contact our patient educator at (800) 747-2820, option 1, or by email at info@aamds.org, for answers on a wide range of questions, including information on treatment options, clinical trials, financial resources, and more.

support connectionThe Support Connection is a national network of trained volunteers, including patients, caregivers, and family members who offer information, personal experience, coping strategies, problem solving skills, and informational resources. To connect with a Support Connection volunteer, call (800) 747-2820, option 1 and speak with our patient educator, who will match you with one of our volunteers. You can also email info@aamds.org.

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AA&mDsiF - Your best resource for medical and personal perspectives on myelodysplastic syndromes (mDs)