CLL Genetic Testing Explained

CLL Genetic Testing Explained from Patient Empowerment Network on Vimeo.

 Genetic testing results can impact a chronic lymphocytic leukemia (CLL) patient’s treatment options and prognosis, but these tests are different from the “hereditary” tests you hear about.  Learn about the types of testing available, how the information is used to guide treatment decisions and clear steps to empower you to work with your healthcare team to access personalized care. Want to Learn More? Download the CLL Genetic Testing  Resource Guide here.

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CLL Genetic Testing Explained

Chronic lymphocytic leukemia, also known as CLL, is a type of blood cancer that occurs when the bone marrow makes too many abnormal or cancerous lymphocytes. It is the most prevalent type of leukemia in adults. Some forms of CLL are slow growing and may not require treatment immediately, if at all. Patients with CLL are monitored closely to determine when, or if, they will need treatment.

How Can You Learn More About Your CLL?

Genetic tests can provide more detail about your specific disease. By using laboratory approaches to identify changes in chromosomes, genes or proteins occurring in your CLL cells, the results can assist your healthcare team in providing better overall care. These tests do not look for genetic changes you inherit or that you pass on to family members. A gene mutation is an abnormal change in a gene’s DNA sequence.

Identifying mutations and changes in chromosomes can help determine:

  • Whether a patient needs closer follow up.
  • A patient’s prognosis and outcome.
  • And the best treatment for that individual person.

The types of genetic tests that physicians use for patients with CLL include:

  • Fluorescence in situ Hybridization, or a FISH Test, which is used to identify specific genes or chromosome changes. This type of test is essential before beginning a treatment regimen.
  • Molecular testing identifies specific gene variations or mutations. Types of Molecular tests include:
  • Polymerase chain reaction, PCR for short
  • DNA Sequencing
  • and Next-Generation Sequencing

Your healthcare team can determine which type of tests are appropriate for you.

Mutations associated with CLL include:

  • Notch1 mutation
  • TP53 mutation
  • and SF3B1 mutation

Your healthcare team will look for the following changes in chromosomes using the FISH test:

  • Deletion 13q
  • Trisomy 12
  • Deletion 11q
  • and Deletion 17p

Patients with Deletion 17p do not respond well to chemotherapy. These patients have a better response to oral targeted agents and should strongly consider a clinical trial for treatment. Prior to treatment, your healthcare team should check for the IGHV mutation. This mutation in CLL patients is a favorable finding, and indicates that the patient may have a slower growing cancer that is easier to treat. Watch and wait, also known as active surveillance, is the period of time before treatment begins in which a patient is monitored closely. When the disease progresses or symptoms occur, your healthcare team will begin treatment.

When it’s time to treat, there a number of approved CLL treatment options Including:

  • Oral targeted therapy
  • Clinical trials
  • Monoclonal antibody therapy
  • Chemotherapy in combination with a monoclonal antibody
  • And stem cell transplant

How Can You Take Action?

  • Make sure you see a CLL specialist.
  • Discuss which tests you should undergo with your doctor.
  • Review the results with your doctor.
  • Do your own research on the findings.
  • Work with your healthcare team to determine a personalized treatment plan for Your CLL.
  • Ask your doctor when you should be re-tested.

Undetectable Minimal Residual Disease (UMRD) Explained

Undetectable Minimal Residual Disease (UMRD) Explained from Patient Empowerment Network on Vimeo.

Dr. Brian Koffman, co-founder of The CLL Society, defines the term undetectable minimal residual disease (UMRD) and explains its role in chronic lymphocytic leukemia (CLL) care.

Dr. Brian Koffman is the cofounder, chief medical officer, and executive vice president of The CLL Society.

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So, “UMRD” stands for “undetectable minimal residual disease.” So, what the heck does that mean?

What that means is that if you got it, you’re in pretty great shape because your CLL has been driven down to such a low level that it’s no longer detectable. Now, that doesn’t mean that you’re cured of the CLL, that doesn’t mean the CLL is gone, but that means your CLL is such a low level that it’s no longer detectable. The minimal residual disease is undetectable; we can’t find it with the best tests that we have.

And, that is very good news because it means your CLL is either potentially cured – and we won’t know that for several years, but there’s some evidence to suggest that some people who reach UMRD are cured of their CLL, or that the CLL’s been knocked down to such a low level, it’ll be years before it reoccurs again. So, I think UMRD is one of the hot terms that’s getting a lot of attention, and it’s one that you wanna be comfortable and familiar with.

How Can Patients Advocate for Genetic Testing?

How Can Patients Advocate for Genetic Testing? from Patient Empowerment Network on Vimeo.

How can chronic lymphocytic leukemia (CLL) patients ensure they are getting the appropriate genetic testing? Dr. Danielle Brander shares resources and advice to help patients become informed and empowered to ask questions and advocate for better care. Want to Learn More? Download the CLL Genetic Testing Resource Guide here.

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

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Dr. Brander:

Patients and their caregivers can advocate for testing by having the information at hand as you meet with your oncology team. There are some tests that are very helpful around the time of diagnosis, especially the FISH test. We talked about how the FISH helps give information about what to expect and what treatment selections to use moving forward, but often these FISH panels also include testing to almost double check and exclude that there’s different type of lymphoma other than CLL present.

So all patients should have FISH at the time of diagnosis regardless of whether they need treatment or not.

There are many good resources online. The NCCN or the National Comprehensive Cancer Network has a guide for not just the treatment but also the diagnosis and initial testing that is helpful for CLL. And there’s a guide for physicians and other oncology team members. And then there’s also a patient-specific guide, and many of these markers are included in that guide and are helpful information that can be brought to the office and also can be helpful supporting information if there’s a concern about insurance coverage.

Another way to advocate would be, in addition to having the resources at hand, is asking what the approval might be for the testing in terms of insurance. And there might be supplemental information that your team or the patient, or their caregivers themselves can provide from these resources that’ll make sure that the testing is covered for patients.

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

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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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.