CLL Genetic Tests: How Do Results Impact Treatment and Care?

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CLL Genetic Tests: How Do Results Impact Treatment and Care? from Patient Empowerment Network on Vimeo. 

Dr. Danielle Brander reviews the types of genetic tests used in chronic lymphocytic leukemia (CLL) and explains the role the results can play in a patient’s treatment and care.

Dr. Danielle Brander is Director of the CLL and Lymphoma Clinical Research Program at Duke Cancer Institute. Learn more about Dr. Brander here.

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How Can Patients Advocate for Genetic Testing?   CLL Genetic Testing Explained Essential Lab Tests for CLL Patients

Transcript:

Dr. Brander:               

There are many types of what we call genetic or genomic testing in CLL. One point that I think needs to be clarified is unlike other malignancies when sometimes we mention genetic testing, the testing in CLL is not testing of all the cells of your body where you’re looking for any genes that were perhaps inherited to your parents, or in your cells that are passed on to offspring.

Rather, just to clarify from the offset, when we talk about genetic or genomic testing, these are characteristics of the leukemia cells themselves. That is, when it becomes a cancer that’s called CLL, some of its genes can change, and those genes can provide helpful information from the time of diagnosis and what perhaps to expect in the years coming forward. And more and more we use these genomic tests to inform and help amongst your treatment options both as first treatments and if the patient requires subsequent treatment.

There are several different types. Some of them involve looking at whole, duplicate, or missing parts of the chromosome so the material that – what holds the genetic material in the leukemia cells.

And one of the very important of this test is a test called FISH. And FISH probes within the chromosomes to look for common abnormalities that are known to be important in CLL. So it doesn’t look at all the chromosomes, but by probing for specific areas, it makes it much more sensitive to be able to test the cells. And there are different patterns that we can talk about again that won’t change whether patients need treatment or not, but are helpful in knowing what to expect and what the best treatment options may be.

Another important test in CLL is a test called the IGHV mutation status, and that’s a big long word and test, but there are two parts of that. One is mutated and one is unmutated, and it sounds backwards, but patients with mutated IGHV may have a longer time to treatment and can have different responses and duration of responses specific to chemotherapy.

Now with the newer drugs that are available for CLL, another point I just want to make is that these tests were mostly originally studied in the era when we only had chemotherapy or chemoimmunotherapy to offer the patient. So, looking at the results of those studies may not inform completely because with the newer drugs, responses can often be seen even for patients that have what we call the higher-risk changes in FISH or IGHV.

The one other type of test that I’ll mention is looking for a mutation in a gene called TP53. Now by FISH testing, we look for deletions of part of the chromosome in the leukemia cell called deletion 17p. That deletes part of the chromosome that codes for your body, building a protein called TP53.

But patients also can have testing for mutations in TP53, not just the deletion. And again, this might point towards what to expect, but importantly really informs options for treatment moving forward. We won’t have time today to get into all the research tests. Those are some of the standard tests that we do to characterize the CLL after diagnosis, and there might be additional testing at the time of treatment or after relapse, and importantly for patients that are able to be involved in research, there’s many other testing that look at different mutations, though they’re not always part of routine clinical care.

There are a couple ways that the results of these tests can impact overall care and treatment discussions. To review, though, importantly as you meet with your team, the results won’t impact to date when you need treatment. There are certain indications for treatment of CLL, and these right now are independent than the results of the testing. Even if FISH identifies what was historically called a high-risk deletion, such as deletion 17p, that won’t change the recommendations to that patients need treated right away.

However, putting the different markers together may inform your team to help counsel you on what to expect moving forward. There are a couple studies looking at patients with higher-risk changes by FISH or with the IGHV unmutated may need treatment sooner than someone that does not have those changes. So it gives you a little information though still just a prediction of maybe what to expect.

Perhaps the greatest impact, though, is at the time of requiring therapy, and that is because patients with either deletion 17p by FISH, or TP53 mutations should never receive traditional chemoimmunotherapy as the first treatment because patients with this type of CLL are really resistant to chemoimmunotherapy, and the novel agents or clinical trials should be explored.

More and more, the test for IGHV at the time of first treatment can also be helpful in choosing amongst options as there were two recent large clinical trials where half the patients received chemotherapy, half the patients received in that particular trial ibrutinib-based therapy as the first treatment. And for patients with especially IGHV unmutated, the responses were much longer for patients that received the novel therapies. In fact, if you look at patients treated with the novel treatment such as ibrutinib or venetoclax, or next-generation inhibitors, there’s really no difference in response whether patients had mutated or unmutated IGHV and the depth of response.

So, it’s still very individualized discussion because there might be other medical problems patients have or specific other reasons not to use the novel targeted drugs.

But in terms of expectation for response and duration of response, that’s how it can be very helpful.

Will Cancer Be Cured By 2020?

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After cardiac diseases, cancer is the second most leading cause of death worldwide. According to WHO, 20% of deaths are down to cancer while in 2018, there were 18 million new cases, along with 9.6 million deaths were reported. Although the number of surveillance within five years after the diagnosis of cancer is 43 million. In the US alone, 1,688,780 new cases and 600,920 cancer-related deaths were reported in 2017 by National Cancer Institute (NCI).

Researchers have conducted meticulous studies to discover new ways to cure this deadly disease. Currently, the most effective treatment options are radiotherapy, chemotherapy, surgery, and hormonal therapy. But the concern is; how close are experts are in finding more effective treatment options for cancer? Many innovative therapies are beginning to pick up steam to defeat the battle against cancer and ideally having fewer side effects than available options.

Cancer is not just a game of winners and losers [1], these innovations are aimed to address the issues of aggressive treatment, recurrence, irreversible side effects that healthcare providers and patients both face. Below are some updates on the most advanced cancer research breakthroughs that have given us hope for better therapies and prevention methods with less harm.

1.   Immunotherapy

Immunotherapy aims to reinforce existing arsenals in our body to fight against cancer cells. Some types of cancers have the characteristic of duping our immune system. However, with the help of in vivo and in vitro experiments, researchers are exploring new ways to deactivate the protective system of cancer cells.

According to Nature Immunology, macrophages that usually eat up harmful foreign bodies and cellular debris fail to obliterate highly aggressive cancer cells. The reason behind this is the macrophages read out two different signals from cancer cells that are meant to rep-el them for cleaning mechanism. Hence, by blocking the dual signaling pathway, researchers can make white blood cells unable to perform their action.

2.   Therapeutic virus vaccines

Innovative virus vaccines are proven to be a surprising weapon to fight against cancer. In the UK, a team of scientists has succeeded to use reovirus against brain cancer cells [2] while not harming healthy cells. It can pass the blood-brain barrier hence opens up the possibilities towards betterment.

Another milestone is the discovery of dendritic vaccines, in which they are extracted from a person’s body and armed with tumor-specific antigens that make them hunt and smash the cancer cells. Then the dose is injected back to the patient’s body to boost the therapy. Some concerns raise as it may have some pitfalls of damaging healthy tissues.

To address this, researchers from North Carolina have developed a bio-responsive scaffold system to hold on both chemotherapy and immunotherapy with better control on targeting tumor.

3.   Nanoparticle revolution

Stakeholders believe that nanoparticles can be a game-changer in the treatment of cancer.  They are précised and are less invasive to target specific cells without harming the surrounding environment. They can be used to give hyperthermic treatment to make tumors shrink.

Researchers are working on self-regulating nanoparticles to target undifferentiated carcinoma cells without damaging healthy tissues. They can be used to target stem cells to treat the resilience of cancers. They can even be loaded with drugs to prevent recurrence of degenerative diseases [3] and can be beneficial in the treatment of invasive carcinomas such as endometrial and breast cancers.

4.   Starvation strategy for tumors

Starving cancer cells to death is a novel method to kill them. There are many studies onboard that prove multiple ways of cutting off cancer cells nutritional supplies. One effective way is to stop the glutamine supply. It will maximize the oxidative stress and induce cell death. Moreover, blocking the supply of vitamin B2 can halter cancer stem cells. Therefore the strategy can help to avoid the toxic effects of chemotherapeutic agents.

5.   Epigenetics

This refers to the alteration of gene expression to dominate the representative action to affect cells at a biological level. Recent advancements have shown that cancer cells can harbor epigenetic modifications [4] to promote progression and eradication of carcinoma.

Scientists have to channelize the potential without triggering Huntington’s disease, and this is the biggest challenge and concern for them that makes them more hopeful. The knowledge can be utilized to treat stubborn tumors and progress enzyme inhibitors for better success rates.

In a nutshell

Shawn Brad, Research content writer at King Essay [5] believes that researches have given us innovate safe ways to cure cancers and studies are running at a good pace; however, curing every type of cancer is definitely a matter of time. Promising studies immensely give us hope on some technological terms for upcoming years.

It is difficult to say that a single approach is going to work for a variety of needs, while much advanced emerging ways can be useful in treatments. Hence, there are optimistic efforts, that make us claim that cancer can be eradicated quickly, and further depth in knowledge can give us more targeted and précised tools to turn the tables.

Resource Links:

[1] Cancer is not just a game of winners and losers

[2] reovirus against brain cancer cells

[3] prevent recurrence of degenerative diseases

[4] harbor epigenetic modifications

[5] King Essay

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Assessing Credible AML Resources and Identifying Research Scams

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Dr. Daniel Pollyea shares advice on vetting credible acute myeloid leukemia (AML) resources and provides words of warning related to potential clinical trial scams.

Dr. Daniel Pollyea is Clinical Director of Leukemia Services in the Division of Medical Oncology, Hematologic Malignancies and Blood and Marrow Transplant at University of Colorado Cancer Center. 

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Transcript:

Ross:                          

You know, when you find out something like this, your tendency might be to jump on the web and start searching for AML. How do you vet those sources that you look at? How do you figure out that their – what would be a sign that they’re bogus sources?

 

Dr. Pollyea:                 

Yeah. I mean, I think this field is so rapidly changing and the treatment that we have, that I would, for the most part, assume that what you’re finding on the web is not relevant and is not an up-to-date resource. So, the resources that I listed, the NCCN, UpToDate, the Leukemia & Lymphoma Society, I should mention.

A very important resource that has up-to-date information, and they have even phone numbers for patients and their families to call to get connected with the proper people in a particular city, so that is a really important resource. But I’d be really, really cautious about what you find on the internet because things are changing so fast in this field. There’s a lot of outdated and misinformation on the internet.

 

Ross:                          

Well, then there’s outright scams. One of the things you mentioned before we went on is be cautious if someone’s asking you to put money upfront, or if it’s a nonmedical facility. What are some things that people should watch out for?

 

Dr. Pollyea:                 

Yeah. So, one of the things that is so important in our area is clinical trials and participating in clinical trials. Patients who opt to do this and receive experimental therapies can sometimes get the treatment of the future, get a drug that’s not currently available through the FDA, but may have a lot of promise.

And this is the way that we fight this disease. We’ve recently had an onslaught of approvals for AML and that’s because the patients being willing to participate in sanctioned clinical trials. So, participating in a sanctioned clinical trial is crucial, and it’s always a recommendation of all leukemia doctors.

When you participate in a conventional clinical trial, you’re asked to sign a consent form that explains what you’re doing and why. There is a confirmation that this has been vetted by an institution’s regulatory board that is prioritizing the safety and well-being of you, the patient. This has been approved by the FDA as a clinical trial. Nobody would ever ask you to pay money. That’s not ethical to participate in a clinical trial. Insurance covers whatever standard of care. And the clinical trial covers anything that isn’t.

So, if you find yourself in a situation where you’re not being asked to sign a consent form, where a clinical trial has not been reviewed by a regulatory board, where your doctor is not a leukemia specialist, where the FDA has not sanctioned the treatment, all of those are alarm signs.

Because there are people out there that are preying on patients in a desperate situation, a very difficult time in their life, and giving them sort of false hope and leading them down paths that are not legitimate.

One easy thing to do to sort of check to see if a clinical trial is legitimate is to go onto clinicaltrials.gov.

This is a resource set up by our national healthcare system that now feeds in every legitimate clinical trial from all over the world, needs to be registered on clinicaltrials.gov. So, if you can’t find your clinical trial on clinicaltrials.gov, I would have a lot skepticism and caution about that.

5 Holistic Methods Used to Process Grief

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The thought of losing someone you love is almost unbearable, but for millions of people each year they must grieve for someone close to them. Grief is an emotion we all face at one time or another in our lives and is completely natural. However, being natural does not make it easy. While we may never truly get over the loss of a loved one [1], there are steps to be taken that can help you process grief and make life a little easier.

Yoga

Grief is an emotional stress that we store within the body and overtime those emotions can help bring us down. Yoga [2] is one way to help loosen that tightness without having it all unravel at once. Yoga allows your mind to soothe yourself by providing mental self-care and at the same time physical activity which is also important for releasing pent up stress or anxiety.

Essential Oils

Essential oils are chemicals that can either be rubbed on the skin or inhaled. Inhaling essential oils helps to stimulate areas of the limbic system that regulate emotion, behavior, long-term memory, breathing, heart rate, and blood pressure.

Each oil, such as rose or sandalwood, provides specific or healing responses depending on the emotion you are trying to inhibit or soothe. For example, rose [3] is commonly used to ease anxiety, depression, headaches, and menstrual cramps.

Getting Enough Sleep

Sleep can be difficult when you are going through a grief cycle [4]. This is because your mind is filled with thoughts about the loss of your loved one. In addition, when you do fall asleep you are likely to be plagued with sleep disruptions such as nightmares. While getting a quality night of sleep can be difficult there are a few things that can be done to help ease yourself into bed. For starters it is important to create an environment to induce sleep. Use dark or calming colors or black out curtains. Essential oils, a white noise machine, and mood music can all help. If all else fails, cuddling up to a loved one like your spouse or pet [5] are shown to fulfill the need for security and comfort.

Exercise

A lack of motivation is one of the most difficult things to overcome when you suffer from grief. Grief can easily swallow you up and keep you hidden from the outside world. This is one of the reasons why exercise is so important for grief sufferers. Endorphins [6] released during exercise reduce our perception of pain – both mental and physical. This helps to create an improved mood and the physical exertion of your body contributes to better sleep, and an overall feeling of accomplishment.

Massage Therapy

Massage therapy [7] utilizes a variety of tools and mechanisms such as oils, music, and level of touch that can help a person experiencing grief. Massage therapy has a long history of improving physical conditions and emotional conditions such as grief. Massage therapy helps to soften the body’s muscle tissues that become when experiencing grief while improving blood circulation an overall state of calm.

Resource Links

[1]  Grief Isn’t Something to Get Over

[2] Grief Yoga

[3] Health Benefits of Rose Essential Oil

[4] Sleep and Grief: Tips and Tricks to Get the Rest You Need

[5] Here’s Why Sleeping With Your Dog Is Actually Good For You

[6] Endorphins: Natural Pain and Stress Fighters

[7] Massage Therapy: What You Need To Know

Cancer Support Community

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What is Personalized Medicine?

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Dr. Elizabeth Bowhay-Carnes defines the often-misunderstood term “personalized medicine” as it relates to your genetic testing results and treatment decisions.

Dr. Elizabeth Bowhay–Carnes is Director of the Adult Non-Malignant Hematology Program and Co-Director of the Adolescent/Young Adult Oncology Program at Mays Cancer Center, home to UT Health San Antonio MD Anderson Cancer Center.

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Transcript:

Dr. Elizabeth Bowhay-Carnes:

When doctors or people within the medical community use a term called personalized medicine, specifically we’re talking about some advanced testing that can be done on a patient’s DNA. Usually, this is talking about a specialized test that is called next-generation sequencing, and that particular test, next generation sequencing, is a technology that allows us to look deeper into a particular patient’s DNA or problems within the DNA of the cancer cell.

We then try to pick treatment options that match that patient’s particular problems with the DNA of their cancer cell. So, you will sometimes hear this particular technology referred to as personalized medicine, and usually we’re talking about next generation sequencing.