Published on September 4, 2020
How Often Should CLL Patients Have CT Scans? When Do Experts Know To Start Treatment?
How often should CLL patients get CT scans or tests such as next generation sequencing and FISH? When do doctors decide to "pull the trigger" and start treatment? If you have a more aggressive form of chronic lymphocytic leukemia, like 17p deletion, should you start with a more intensive treatment option? Where are we with combination therapies? Host Andrew Schorr gets the answers to these questions from CLL expert Dr. Richard Furman from Weill Cornell Medicine.
This is Part 3 of a 4-part series on CLL. Watch all segments in the series below:
- Part 1: Latest News on BTK Inhibitors for CLL
- Part 2: Monitoring CLL: Determining Treatment Plan and MRD Testing
- Part 4: Risk of Secondary Cancers When You Have CLL
This program is sponsored by AbbVie, Inc., Genentech, Inc. and Adaptive Biotechnologies. These organizations have no editorial control. It is produced by Patient Power. Patient Power is solely responsible for program content.
Transcript | Latest CLL Research on Scans, Treatments and 17p Deletion
How Effective are CT Scans for CLL Patients?
Let's go on about treatment and monitoring. One lady wrote in and she said, “well, my doctor keeps having me have CT scans, where does CT scans and that monitoring, and radiation fit in related to CLL?”
It really doesn't. The truth is, is Rai stage, as it was first developed and validated in 1973 by Dr. Rai, did not use CT scans at all. And I do, I am concerned about radiation exposure and when CLL patients were living, had a median life expectancy of 7 to 9 years. And that was back in the days of only having chemotherapy. Radiation exposure didn't matter. My hope is that CKK patients can now enjoy normal longevity. So, all of a sudden radiation exposure does matter. And so outside of a clinical trial, I very rarely will use CT scans. And it's really important to keep in mind that the rise in the white count, the drop in the hemoglobin, the drop in the platelet count and the lymphadenopathy and splenomegaly evaluated on exam will suffice for almost all patients.
So the criteria for going off of watch and wait is that you're just tired, swollen lymph nodes and large spleen, night sweats, when do you pull the trigger?
So I'd like to first off, the most important thing to remember is that common things occur commonly. So someone did a study 70% of CLL patients have fatigue as a symptom, 80% of New Yorkers have fatigue. So having CLL protects you from fatigue based upon those data. So, I think it's important to keep in mind that the most common cause of fatigue in a CLL patient is no different than harmless common cause of fatigue in any person. And it's rare that fatigue would be caused without the setting of having a large tumor burden or an anemia. And so it's important to really look at the entire perspective. There's a lot of people who have undiagnosed sleep apnea or other issues that might cause fatigue that would really be unfortunate to blame the CLL or initiate therapy.
The most common reasons for initiating therapy really are going to be a rapid doubling of the white count. And that's typically going to be based upon six months or less, a drop in the hemoglobin below 11 or a drop in the platelet count below 100,000. And what we also do to see is that patients will develop either large lymphadenopathy. And it's important to remember that the CLL lymph nodes are well-behaved. They're not going to compress anyone's trachea. They're not going to compress a blood vessel, but they can get bulky and that's a sign of significant disease burden or a large spleen and that just really indicates that the disease is active and that there's really no advantage to further watch and wait.
Related to different groups. You said that most people, 80% are garden variety, CLL, and there's 20% where it's more aggressive. What are the tests you're doing and how does that relate to prognosis where patient comes to you, you do these tests and you say, "This is your version of CLL."
So I think there's first off, no substitute for historical behavior. All right. Unlike the stock market past behavior does predict future behavior for most CLL patients. Now we have over a hundred different prognostic markers that we can assess in CLL patients. And the truth is, it's only very few who are really relevant. So whether or not you're mutated and your immunoglobulins genes are unmutated, that will determine your time to progression, but it doesn't determine your time to treatment. And it doesn't determine your response to our novel agents.
So yes, you may need your treatment to initiate a little bit sooner, but if everyone does equally well, and our goal is actually overall survival, then it really is fine either way. So the prognostic markers that are going to really be relevant are the ones that determine patients more likely to do less well on BTK inhibitors. And so I think 17p deletion, complex karyotype TP53 mutation. Those are really the ones that I think that are most relevant. So I do interface FISH in all my patients. I also do next generation sequencing in order to look for mutations in the TP53 gene, which is the gene that's actually missing on 17p deleted cells or in 17p deleted cells. So those are the ones that I think that are most important and the ones that are really necessary for the best planning of patients.
What Does 17p Deletion Mean for CLL Patients?
Okay. So if somebody has this 17p deletion, do you tell them right off the bat, I think you have a more aggressive CLL, we're going to have to treat it with bigger guns or I'm going to recommend a clinical trial to you?
So the truth is that's what your prognostic markers are, really doesn't tell us how to treat you. And that's an important distinction. The treatment is still going to be the treatment. Now we actually, I do have patients with 17p deletions whose diseases remain very stable for 20 years. And it's important to remember that man is inherently unpredictable, except for the use of statistics when you can know exactly how the entire population will do. But never the individual. And so it still is based upon waiting for that disease activity to start. Now, if I have a patient who's 17p deleted and the white count starts to grow, I'm going to be a little bit more quick to initiate therapy than I might in a non-17p deleted patient. But we still have no reason to initiate therapy in a patient who's not showing active disease. And I still think that the best therapy for all the patients is really going to be the same, regardless of what their prognostics are.
Developments in CLL Treatment
Dr. Furman, you're involved in research and people have a lot of questions. They say, well, if we have these powerful newer medicines, what about combining them for a bigger bang, basically a cure or whatever, so that people can go on with their lives and not even think about CLL.
So really, we've done that. So there's already been one large study combining ibrutinib (Imbruvica) and venetoclax (Venclexta), which really was very successful of course, unofficially because the data aren't mature yet, but it definitely achieved very deep responses in almost all patients. There are some side effects when you combine the ibrutinib with venetoclax and so we are looking for other partners to combine with venetoclax because the synergy really comes from a B-cell receptor antagonist. So, ibrutinib, acalabrutinib (Calquence), zanubrutinib (Brukinsa), or duvelisib (Copiktra), idelalisib (Zydelig) being combined with the venetoclax. Really generates a very, very powerful depletion of the clone. And so that combination is absolutely what most of us are studying at this time. We'd have been combinations of anti-CD20 with all of these agents as well and I think the anti-CD 20 adds relatively little to the novel agent, whereas the novel agent combined with another novel agent is really a very powerful combination.
Okay. Someone might take two CLL pills instead of one, and what you're saying is the monoclonal antibodies may fade in the background, the infused therapies or injectable therapies, things like that.
Alright. So now, somebody said that there was a journal article about a PARP inhibitor. This is a different kind of medicine, and that might be for a certain subtype of CLL. Any thoughts about that?
We really currently have no clinical data supporting the use of PARP inhibitors and particular in CLL. They really are very early in development and really been focused more on solid tumors then they have on other linking to them. Everything works in vitro or in the laboratory and it's important to keep in mind that there really isn't great preclinical data suggesting that PARP inhibitors will be revolutionary for CLL treatment.
We talked about the BTK inhibitors and you have some people on it many years, and you have other people where they've been on venetoclax probably initially with a monoclonal antibody. And you're looking at combining different pills, like venetoclax with the other drugs to see whether we had a bigger bang and you're encouraged by that.
Okay. So, we'll see if we're headed there. And related to side effect profiles, you can personalize that to the patient. Do they have what you call comorbidities, or having certain side effects and can they switch to one of the other classes of drugs?
Not even one of the other classes, but sometimes if it's a side effect issue, I will try a second BTK inhibitor in a patient to see if I can still get the same efficacy without the side effect recurring.
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