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Patient Considerations That Impact MPN Treatment Decisions

Patient Considerations That Impact MPN Treatment Decisions from Patient Empowerment Network on Vimeo.

How can personal choices play a role in your MPN care? Dr. John Mascarenhas reviews factors that should be considered, including lifestyle and overall health, when choosing therapy for essential thrombocythemia (ET), polycythemia vera (PV), or myelofibrosis (MF).

Dr. John Mascarenhas is Associate Professor of Medicine at the Icahn School of Medicine at Mount Sinai (ISMMS) and the Director of the Adult Leukemia Program and Leader of Clinical Investigation within the Myeloproliferative Disorders Program at Mount Sinai. Learn more about Dr. Mascarenhas, here.

See More from INSIST! MPNs

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Transcript

Katherine Banwell:

Outside of testing, what other factors should be considered when choosing treatment?

Dr. Mascarenhas:       

I think patient expectation. So, sometimes physicians and family will impose what they want for a patient, and that may not be what the patient really wants. So, I have learned over the years that it’s crucial to make sure that you understand the patient and what the patient’s expectations, desires, and that’s influenced by the life they’ve lead or the remaining life that they want to live and their own personal religious and spiritual beliefs.

So, I think knowing your patient and understanding what their expectations are, it’s fundamental, and sometimes, it’s overlooked. So, understanding that, I think, is very crucial. And then, dividing what are the objectives of the treatment in a given patient? Is it really to improve anemia in some patient versus perhaps a different patient, it may be to improve their quality of life and reduce their symptom burden. And then in other patients, it may be purely trying to cure the disease with therapies that may be aggressive, which may not be appropriate for an older patient where toxicity could outweigh any potential benefit of survival or longevity. So, you really have to have a discussion with the patient or caregivers, and then define what are the goals in that individual to personalize that approach for that patient.

Katherine Banwell:                  

Right. Right. And, there’s the patient’s overall health, comorbidities, other things like that?

Dr. Mascarenhas:       

Yeah, because we are not treating a disease in isolation usually. So, patients come with baggage posed of past diseases, current diseases.

And sometimes patients are not “fit” for certain types of therapies because they may be sick or they may have organ dysfunction that would make certain types of treatment approaches ill-advised because the toxicity could be higher. So, absolutely, you need to know their comorbid index, how much comorbidities they have and also their performance status, how active and how well they are in general.

Katherine Banwell:                  

Are there specific biomarkers that may affect prognosis or treatment?

Dr. Mascarenhas:       

So, yes and no. I mean, I think that’s an area of intense interest and research. So, we have identified certain biomarkers that have, as I mentioned, prognostic significance, and that may influence treatment decisions. So, patients who have, for example, as we discussed next-generation sequencing and we see their mutations that are present, if they have an accumulation of high molecular risk mutations, that may give us a sense that perhaps that patient may not enjoy the full benefit and duration of benefit of, for example, a JAK inhibitor as another patient that has a less complex disease.

And, that doesn’t necessarily mean that the therapy is not appropriate for the patient. But it may help us plan and be prepared to move on to the next therapy sooner or to be more vigilant for changes that would tell us it’s time to move on. So, I think they help us maybe get a general sense of things and put things into perspective. They don’t always necessarily inform us on a change in therapy immediately or the next or the most immediate therapy. But I do think that that will change because I would predict in the next five to 10 years, I think that the number of available drugs for myelofibrosis, for example, will likely double from what it is now. I think we will have an armamentarium to choose from, and what we will learn from trials that are ongoing is there may be certain profiles, mutations, chromosomal profiles, other clinical variable profiles that we will learn from these trials that will help us to find upfront, “Well, this profile really should go with his medication. That profile should go with that medication.”

An early of example that would be we’re learning that not all patients with the JAK2 mutation are created equal, that you can have different burdens of JAK2 mutation.

And, patients with low burden JAK2 mutation, for example, may fare better with up a specific JAK to inhibitor like pacritinib than patients who get treated with other JAK inhibitors like ruxolitinib.

So, there are differences even within patient defined by mutation that may help us predict which of the JAK inhibitors, as an example, may be more appropriate as a first-line therapy. So, I think that will evolve more so over the next five to 10 years.

What Are the Goals of DLBCL Treatment?

What Are the Goals of DLBCL Treatment? from Patient Empowerment Network on Vimeo.

A diffuse large B-cell lymphoma (DLBCL) treatment plan may have different goals depending on the patient. Expert Dr. Loretta Nastoupil provides an overview of factors that play into treatment decisions and shares information about current and emerging DLBCL treatments.

Dr. Loretta Nastoupil is Director of the Lymphoma Outcomes Database in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. Learn more about Dr. Nastoupil, here.

See More From The Pro-Active DLBCL Patient Toolkit


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Factors that Guide a DLBCL Treatment Decision

DLBCL Treatment Decisions: What’s Right for You?


Transcript:

Katherine:

Many factors come in to play when making a treatment decision, including a patient’s age and overall health. So, let’s walk through some of these considerations. Let’s start with treatment goals. What does this mean exactly? And what are the goals of treatment for DLBCL?

Dr. Nastoupil:

Great questions. For diffuse large B-cell lymphoma, my goal was that I want to eradicate this disease with one course of therapy. Now one course of therapy, again, may mean six cycles of treatment, or it may mean three to four plus/minus radiation. And that kind of gets back to the discussion we just had with stage. But the goal is to make it go away and never come back. Now, oncologists are eternal optimists.

And I saw this because we would not be oncologists if we weren’t always focused and hoping for the best outcomes for our patients.

Katherine:

Sure.

Dr. Nastoupil:

So, we, generally, when we’re counseling patients tend to keep the focus on what is the chance that I can cure this, and we use words like cure oftentimes. But there’s always those caveats. And those caveats are – we can’t really look into our crystal ball and predict the future for every given patient. So, we use tools to help us risk stratify patients, meaning if we took 100 people like a given person, we could predict the outcome for the majority of those patients.

So, with diffuse large B-cell lymphoma with no high-risk features – so, that gets back to the molecular subtype. Do they have double hit features – yes or no? The stage and something we call IPI, International Prognostic Index, that takes into account some clinical features. As you mentioned, patient specific factors, their age, their stage, some lab values, whether or not they have more than one extranodal variable. Then we can generally predict.

Again, if I have 100 patients with good risk IPI, 80 percent of them are likely to be cured and alive and well five to 10 years later. If I have someone with poor risk features that may not change exactly what I do for that patient, but that may help them and me in terms of should I be pursuing a trial to potentially have access to something that’s better than this standard option? Or how does this impact their planning?

Some people are close to retirement. Some people have specific life goals, such as a wedding or an anniversary that sometimes we use those sorts of calculators to best predict the future to inform some of that treatment. So, those are what we call sort of the characteristics coming into treatment.

There are comorbidities or sort of concomitant medical problems, such as heart disease, sometimes diabetes. But, generally, more often than not, it’s how healthy your heart is because my objective with treatment is to cure this.

Cure generally results from chemotherapy. And we can spend some time talking about why have we not moved away from chemotherapy in this disease? But, generally, that does involve chemo because that’s generally how I can eradicate this tumor.

But there are certain situations where that chemo may not be beneficial to a given a patient. It usually has to do with how healthy their heart function is at baseline. So, again, we look at all of these factors. What is their risk with the disease? What is their risk from the toxicity of treatment? And am I able to achieve that goal, which is to eradicate the disease?

Katherine:

Well, let’s talk about chemotherapy. Why is that still part of the regimen in a treatment plan?

Dr. Nastoupil:

Yes, I’m going to borrow an analogy that one of my colleagues Jason Westin uses all the time. The CHOP chemotherapy that is the backbone of our treatment for diffuse large B-cell lymphoma was developed in 1976.

There is no other technology that we would commonly use in our day to day. You wouldn’t still be driving your car you had in 1976. Clearly, our methods of communication in regards to phones have changed dramatically. So, why are we still using chemotherapy that was developed in 1976?

Katherine:

True.

Dr. Nastoupil:

Well, it’s not for lack of trying. Over the last four or five decades, we have been trying to improve upon this. And it works. It works for at least 60 percent of patients. When we tack on targeted therapy, such as immune

therapy where we use an antibody that will stick to the surface of a marker on that lymphoma cell and then use the immune system to do some of the heavy lifting, we can probably improve those cure rates from 60 percent to potentially as high as 80 percent. That’s really been the only substantial improvement we’ve made.

Now, there is one caveat. So, just recently, we heard a press release of the POLARIX study, which is the first trial in the last four decades that could potentially replace R-CHOP as the standard of care.

We don’t have the full results yet. It’s essentially utilizing a drug called polatuzumab, which is an antibody drug conjugate. It’s essentially chemo on a stick. But we’re delivering chemo specifically to (CD)79b, which is a target on B cell lymphomas and modifying the CHOPs. We’re not getting rid of chemo altogether. We’re dropping one of the chemotherapy agents and replacing it with this targeted agent. So, it’s essentially CHOP plus rituximab and polatuzumab might be the new standard.

But, again, that’s based off many, many efforts to try and replace CHOP. And we’re making slow incremental improvements, but we’re still keeping the therapies that tend to work. 

Which CLL Treatment Approach Could be Right for You?

Which CLL Treatment Approach Could be Right for You? from Patient Empowerment Network on Vimeo.

Which CLL treatment approach might be best for your individual disease? This animated video walks through important considerations that help guide treatment decisions, including genetic testing results, lifestyle factors and patient preference. 

See More From The Pro-Active CLL Patient Toolkit


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CLL Treatment Decisions: What Path is Best for YOU?

 How to Be A Partner in Your CLL Care  Key CLL Treatment Decision-Making Factors

Transcript:

Hi, I’m Christy. I’m a nurse practitioner and I specialize in chronic lymphocytic leukemia, or CLL. With a variety of available treatment options, CLL patients often wonder which approach might be best for their individual disease.

Before we walk through the information that goes into choosing a treatment approach, I want to remind you that this video is intended to help educate CLL patients and their loved ones and shouldn’t be a replacement for advice from your doctor.

So, how is a treatment path determined?

CLL physicians will typically consider several key factors to help guide the decision.

When many CLL patients are first diagnosed, their medical team may use an approach called “watch and wait” or “active surveillance.” This means that treatment won’t begin immediately. Their healthcare team will monitor their CLL via in-person visits and lab testing. And, some patients may never even need treatment, depending on their individual situation.

But, if bloodwork indicates advanced disease, enlarged, bothersome lymph nodes develop, or, if symptoms like fatigue and night sweats are negatively affecting a patient’s daily life, then it may be time to treat the CLL.

Physicians typically consider a patient’s age, overall health, and existing conditions before they suggest an approach. There are also several tests on the CLL cells that may help guide treatment decisions.

Physicians use immune globulin heavy chain gene, also known as IGHV, mutational analysis to determine whether a patient is IGHV mutated or unmutated.

In IGHV mutation analysis testing, being “mutated” is a favorable finding. 

If a patient’s IGHV status is mutated, and, depending on other factors such as age and overall health, the physician may recommend a treatment called FCR. FCR stands for the drugs used in this approach, which are two chemotherapy drugs combined with a targeted treatment that is a monoclonal antibody.  

However, it is important to realize that due to side effects and other risks, chemotherapy is not for everybody. Non-chemotherapy treatments work very well for IGHV mutated patients as well as unmutated patients.

If a patient has unmutated IGHV, then a targeted treatment or a clinical trial might be more effective.

Molecular testing, also known as genetic testing, can identify specific genes, proteins, chromosome changes, and other factors unique to your CLL.

The results can provide your healthcare team with information related to prognosis, risk and which therapy may be most effective in treating your disease.  

One of the most widely used tests is call a FISH test and it looks for specific changes in the chromosomes of your CLL cells.  These specific changes can help understand how well certain treatments are likely to work for you. 

For example, patients with the chromosome abnormality “17p deletion” may have higher-risk disease and will not respond well to chemotherapies such as FCR. An oral targeted treatment approach or a clinical trial will be more effective in patients with 17p deletion.

There are several types of targeted treatments that are currently approved to treat CLL including:

  • Monoclonal Antibodies, which work by targeting specific proteins on cancer cells.
  • And, Kinase Inhibitors, which work by blocking proteins that tell the cancer cell to grow and survive.
  • A combination of treatment approaches may also be considered.

Before you start any treatment, it’s essential to ask your doctor if you have had relevant CLL genetic testing, including FISH testing, and what the results could mean for you.

Finally, one of the most important factors that your healthcare team will consider is YOUR treatment goals. 

It’s very important to consider a treatment’s course and potential side effects.

With the many options available today to treat CLL, you will be able to get effective treatment. How your treatment choice affects your other health conditions and your lifestyle is essential.

Remember, you are a partner in your care and have an active voice in finding the best treatment for you.

When treatment is discussed may be a good time to consider a second opinion or a consult with a specialist.  If you don’t feel supported or an active member of your team, then it is always best to get another opinion if you are able.

So, how can you put this information to work for you and help improve your care?

  • Talk to your physician about what you’ve learned.
  • Ask about testing mentioned in this video and whether you need to be retested over time.
  • Discuss clinical trials with your physician.
  • Visit credible resources to stay up to date on CLL information.

Visit powerfulpatients.org/cll to learn more about CLL.

5 Simple Habits To Promote A Healthier Lifestyle

We all know that life can throw us some curveballs…so one of the biggest questions many people have is, how do we maintain a healthy lifestyle while juggling everything else happening on a daily basis? The best answer is to form simple habits to incorporate into your everyday routine. This way you don’t have to worry about adding anything else to your day or changing your lifestyle — think of it this way… we’ll work smarter, not harder! Below, are 5 simple, and easy habits to form in order to promote a healthier lifestyle!

1. Create A Healthy Working Space

We spend hours a day working to benefit our careers or carry out a customers’ needs, but often times overlook our own personal needs. If you’re going to be glued to an office space or work computer, make it benefit not only your career goals, but your health goals too! Try adding a standing desk to your office, or swap out those pop-able munchies for a stash of healthy office snacks.

2. Drink Water With Every Meal

One of the easiest ways to maintain a healthy lifestyle and diet is to drink more water! Our bodies need and crave water to carry out basic functions throughout the day, and upping your water intake will result in numerous health benefits. From improving your hair and skin, to maintaining a healthy blood pressure and even losing weight, your body will surely thank you! Try replacing your go-to beverage with water during mealtimes and after just a few weeks you’ll be shocked at the results!

3. Sleep 7 – 9 Hours Each Night

Whether it’s stress, maintaining your social life, grief, or staying up to watch your latest Netflix binge, it’s very easy for life to get in the way of healthy sleeping patterns. However, giving your body a break and making consistent sleep (7- 9 hours each night) a priority is a MUST. A solution could be as easy as finding the best mattress to compliment your sleeping habits, or using natural remedies like meditation to relax before bed. Another tip for those having trouble sleeping, is to keep a strict sleeping schedule: Wake up and go to bed around the same time every night. That way, your body becomes used to this routine, and prepares you for sleep at the same time each night.

4. Drink Green Tea

Have you been searching for the fountain of youth? Well here’s a secret. One exists. In the form of Green Tea. Other than water, it’s the healthiest beverage out there. It’s packed with antioxidants that improve brain function, regulate metabolism, and ultimately keeps your body looking and feeling young! Bonus: Green Tea contains some caffeine, so instead of loading up on 4 cups of coffee to get you through the day, try replacing one or two cups with Green Tea.

5. Turn TV Time Into Exercise Time

Imagine this. You’re working late, you have to make dinner for your family, AND make sure you tune into Monday Night’s episode of The Bachelor before bed. Unfortunately, you didn’t have time to workout. Or so you thought… Here are a few simple workouts that you can perform in small spaces, such as your living room or bedroom during TV time and/or commercial breaks!

Epigenetics

Why your cancer-creating habits can affect your children (and we’re not talking about second-hand smoke).

It’s hard enough being a parent.  There are no “Parenting for Idiots” books out there.  We just bumble along, trying our best to inoculate our children from our worst selves and influence them with our best.

But like many humans, we may hit the potato chips a bit hard, make exercise the last task on our ever-lengthening “to do” list, and find ourselves doing things we know may not be good for us.

But the science of epigenetics is now telling us that we’re not only influencing our own health but those of our children – genetically.

Here’s how it works.  Epigenetics looks at the way genes express or don’t express themselves as we age.  Those gene changes are thought to be influenced directly as a result of our nutrition and behavior, as well as exposure to toxins in our environment.  In a sense, it’s a hybrid of hereditary disease and lifestyle choices.

An experimental study was done by Stanford University scientist Anne Brunet and colleagues. They noticed that nematodes (a type of worm) had varying lifespans.  Some were exceptionally long-lived and passed that trait through three generations.  Others lived much shorter lives. Yet all the worms, both the old sages and the early departers, were genetically identical.

How is this possible?

The answer lies in epigenetics.  Some of the worms had experienced a change during their lifetimes that affected certain gene expressions that regulated lifespan.  They passed that gene expression through reproduction, even though it had not been part of their initial DNA makeup.

A human version of this can be found in the cases involving the synthetic estrogen compound  diethylstilbestrol (DES).  This was given to women in the 1950’s to prevent miscarriages.  Later it was discovered that DES mothers gave birth to DES affected daughters, increasing their risks for vaginal, breast, and ovarian cancers. Ironically, it also made DES daughters more prone to miscarriage.  The mechanism for this phenomenon is now believed to be epigenetics which facilitated the altered maternal DNA to be passed down to their daughters.

It must be noted the study of epigenetics is in its infancy.  Clear-cut examples of it, like noted above, are rare.  But scientists now have a new understanding that our lifestyle choices and exposure to environmental toxins can affect sperm and egg DNA, and thereby set up new generations for cancer risk in ways that cannot be explained through traditional genetic pathways.


Sources:

https://blogs.scientificamerican.com/guest-blog/epigenetics-a-turning-point-in-our-understanding-of-heredity/

http://www.bu.edu/news/2014/09/15/epigenetic-drugs-a-hope-to-treat-cancer-resistance-and-reduce-cancer-relapse/

How Your Lifestyle Can Affect Genes That Cause Cancer

There are two schools of thinking about cancer.  School one says that cancer is a hereditary disease, passed from generation to generation.  A good example of this are women who possess the BRCA1 and BRCA2 gene mutation.  Women with this mutation have a 70% lifetime risk of developing breast and/or ovarian cancer.  Angelina Jolie, for example, lost her mother and aunt to cancer and was subsequently found to have the same mutation.

The second school says that cancer can occur due to lifestyle choices.  A good example of this is cigarette smoking. It is the number cause of lung cancer, linked to 80 – 90% of lung cancer cases.

Recently, researchers at the Boston University School of Medicine have introduced another theory about the development of cancer.  They proposed that there are processes within our cells that activate certain sequences of DNA.  Those processes act as on/off switches for the development of cancer.

This idea is based on the evolving science of epigenetics. Epigenetics looks at the way genes express or don’t express themselves as we age.  Those gene changes are thought to be influenced directly as a result of our nutrition and behavior, as well as exposure to toxins in our environment.  In a sense, it’s a hybrid of hereditary disease and lifestyle choices.

Epigenetics is a normal process in our bodies.  For example, all of our DNA is the same, yet cells develop into liver cells, brain cells, muscle cells, etc. because of the way epigenetics turns on and off different cell processes.  But our lifestyle choices can impact the way genes express themselves as well.

Perhaps you’ve heard the expression “Sitting is the new smoking.”  The reason for this is due to research on lifestyle and cancer.  The results of dozens of surveys found that a sedentary lifestyle increases the risks of cancer, specifically colon cancer.  Subjects who spent most of their day sitting were 24% more likely to get colon cancer.  People who watched the most television had a 54% greater risk than those who watched fewer hours.  Uterine cancer was also affected by sitting; women who were the most inactive experienced a 32% great risk.  The female T.V. watchers fared worse; those who watched the most television has a 66% risk of developing uterine cancer.

In all these cases, it’s not the inactivity per se that causes cancer to develop.  It’s the processes of epigenetics that are affected by inactivity that can cause cancer.

It’s a complicated and exciting time.  Next month, more on how unhealthy habits are incorporated into our DNA and passed onto our children.


Sources:

https://blogs.scientificamerican.com/guest-blog/lifestyle-choices-could-affect-gene-sequences-that-code-for-cancer/

http://www.nature.com/scitable/topicpage/epigenetic-influences-and-disease-895

http://www.whatisepigenetics.com/fundamentals/2/