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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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Transcript:

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.

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.

See More From Your CLL Navigator

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Transcript:

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.

Essential Lab Tests for CLL Patients

Essential Lab Tests for CLL Patients from Patient Empowerment Network on Vimeo

See More From The Path to CLL Empowerment

Dr. Danielle Brander provides an overview of essential lab testing for chronic lymphocytic leukemia (CLL) patients and discusses which tests should be repeated over time.

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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Transcript:

Dr. Brander:               

So, there are additional laboratory tests besides the genomic or the prognostic markers that patients should have at the time of diagnosis. One that all patients have is a test called the flow cytometry, and that is done often for CLL patients on the peripheral blood. It may also be done on the lymph node or the bone marrow. And this is a profile of the surface of the cells that help your pathologist and your oncologist to confirm that this looks like CLL.

So most patients when they’re told of the diagnosis will have this either from the blood or it’s found on the lymph node. Notably, it’s not required in all patients, and most patients, in fact, to have a bone marrow biopsy at the time of diagnosis unless there’s a concern about other blood counts being low, and it’s not clear why that is going on.

Most of the other tests besides the prognostic genomic genetic markers that we talked about such as FISH, or IGHV, or TP53 are routine tests. So patients will have a repeat blood count, and this should be a blood count with a differential of the white blood count. CLL is a problem of a type of white cells called lymphocytes. So on the differential of the types of white cells you’ll see the lymphocytes are usually marked clearly elevated. But the differential also makes sure that there’s no low other white blood cells such as neutrophils, which are important in fighting bacterial infection.

It’s also a good idea to have at the time – and most patients will – a baseline chemistry, which include the kidney and the liver function. Though definitely not common, some patients can have involvement of CLL of the liver or kidneys.

This is pretty rare, especially around the time of diagnosis. It’s helpful to have those baseline tests. It’s also helpful because the median age of diagnosis of CLL is usually the early 70s, and so a repeat of the baseline kidney and liver function might find other chronic health problems that are important to know moving forward.

Some of the other tests, baseline labs, are more patient specific, and might need follow-up. For example, if the blood count revealed anemia, which is a low hemoglobin or hematocrit, the cells that carry oxygen, your treating team might want to order additional tests for anemia and make sure that the anemia isn’t due to something totally unrelated to the CLL such as iron deficiency or B12 deficiency, etc. So, there might be additional lab tests depending on the additional screening tests that are obtained at that time.

One other test that I’ll – or two other tests that I’ll mention at diagnosis, 1.) Is immunoglobulins, mostly for patients that have had a problem with recurrent infections because patients can have low antibody levels associated with CLL, even if it’s not been treated. So, your team – if recurrent infections have been a problem – may check for those antibody levels, those immunoglobulin levels. A second test that can be helpful at baseline is a test called SPEP or serum protein electrophoresis, which looks for extra proteins in the blood. And again, this can be seen with CLL and other lymphomas, and especially depending on patient’s symptoms, your physician, and treating team might want to obtain those labs.

Again, there are good resources online including the NCCN, CLL and leukemia patient-specific sites that might give a better outline beyond what we can cover today of tests that might be helpful in your specific case.

There are labs and tests in CLL that are repeated over time. Two of the common ones obtained at baseline, the complete blood count and the chemistry, will usually be repeated at every visit after diagnosis for patients not being treated at the time of diagnosis. They’re part of the monitoring, so every three or four months after you’re diagnosed when you see your oncologist and you have an exam, your history of how you’ve been doing, and labs taken, the white count and the chemistries are all to be followed with time.

At the time of treatment, there’s often additional tests that might be done depending on the type of treatment you’re receiving to make sure you don’t have a specific risk for recurrent reactivation of infections, for example. So the testing might change at the time of treatment. And specific to the prognostic biomarkers, the genomic or genetic testing of the CLL that we mentioned, some of them are repeated with time and some aren’t. The FISH, which is obtained at the time of diagnosis is recommended to be repeated. If patients have treatment, the CLL goes into response, and then relapses because the FISH testing can change with time.

The IGHV mutation status, however, as long as it was felt to be an adequate appropriate sample, is a characteristic of the leukemia that doesn’t change with time and would not be repeated. Similar to FISH, it’s a good idea to test the TP53 at the – not always at the time of diagnosis, but before treatment to make sure there’s not TP53 mutation.

But then similar to FISH, if the CLL goes into response and relapses, it’s advisable to repeat the TP53 as that can change as patients have different treatment options and they both help to, as mentioned, inform the first treatment. They’re also helpful to have in mind as patients are being followed on treatments because some patients have a higher risk of the treatment to stop working, for example, if there are higher-risk genomic changes.

 

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.

See More From Your CLL Navigator

Related Resources

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.