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iwCLL 2021 | Prediction and prognostication methods for CLL

Arnon Kater, MD, PhD, University of Amsterdam, Amsterdam, Netherlands, shares his views on current prediction and prognostication methods for the management of chronic lymphocytic leukemia (CLL). Prof. Kater explains that del(17p) is currently the only genetic marker that is relevant for clinical decision making and further discusses the prognostic value of complex karyotype. In addition, Prof. Kater argues that CT scans are still relevant in the context of CLL, but only to assess the risk of tumor lysis syndrome in patients taking drugs like venetoclax. Finally, Prof. Kater comments on the current discussion about BTK inhibitor-related cardiotoxicity. This interview took place at the 19th International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Biennial Meeting, held virtually in 2021.

Transcript (edited for clarity)

The problem is, or the challenge is, how can we pre-start a treatment, best predict which patient will do good on which therapies? And what I pointed out is that the iwCLL 2018 criteria is kind of a starting point, saying if you look to all those factors that you are a yes or no recommended to do with the still dilates. And I made a few conclusions.

One is that, outside trials in iwCLL, we are still supposed to do the complete FISH panel...

The problem is, or the challenge is, how can we pre-start a treatment, best predict which patient will do good on which therapies? And what I pointed out is that the iwCLL 2018 criteria is kind of a starting point, saying if you look to all those factors that you are a yes or no recommended to do with the still dilates. And I made a few conclusions.

One is that, outside trials in iwCLL, we are still supposed to do the complete FISH panel. And the question is, is there any prognostic or predictive value in other chromosome stain del(17p)? And I think there’s actually not. Del(11q) which is still, also in very recent trials, used to randomize or to stratify. I think that’s a bit obsolete now, because there is the addition of R to FC, and with all the new agents, there is no clear better or worse prognosis for 11q. patients. Same is true for trisomy 12. So, I think 17p you really should do with young markers. It’s not that relevant for clinical decision-making.

Then I made a point about complex karyotype. I think there was so much evidence now that either CBA, so chromosomal banding analysis, more the very laborious, old fashioned way, you can say, of looking at chromosomes or maybe the more modern and maybe more easy as long as we can standardize it, way of doing it is by digital assays. So, you get to know the complexity, I think that information on complexity, where you have to very sharply look at the definition, three or more, or probably better five or more aberrations. I think that is very predictable patient with a poor prognosis, we might think of a more intensified treatments than other treatments.

I discussed the role of CT scans, forever, actually, it was very big discussions in the iwCLL, whether or not the CT scan should be mandatory, like we do for lymphoma. For a long time, experts have said, well, outside trials there is no additional value to do a CT scan in a leukemia kind of disease. And I think that also changed, specifically, when we now have drugs like venetoclax where you use the CT scan, not so much to know whether a patient should be treated or not, you do that on physical examination and on blood values, but to assess the risk of a patient and how intense you should monitor the patient for risk of tumor lysis syndrome. I think there is a role.

Then I discussed also the role of CT scans, which is always almost mandatory every six months or even sometimes more frequent in mostly pharmaceutical sponsored trials. And although you get very quick data, so you see very much earlier progression if you do CT scans and if you’re able to do a physical examination and by blood tests. The question really is, how worthwhile it is, because we noticed from the time of progression till time to next treatment, there can be months and even in some studies, years in between. So, the question is how relevant is that?

So, to conclude, the CT scan I think you should do it if you want to think of a therapy which, like venetoclax, where a CT scan will help you to guide how intense your patients should be monitored. For prognostication and for following the patient, I don’t think there is a place outside trials.

And the last point I made is more the patient-related factor. And that is that we make a very big thing now, very lively discussions on BTK inhibitors, and which BTK inhibitor is the best one to prevent cardiac toxicity. And my problem there is that we don’t really have invested enough, I think, in developing good tools to predict which patient is really at risk or not.

So, it’s interesting, and it’s helpful that we have maybe some inhibitors that give, instead of, let’s say 10% chance of A-Fib into 5 or 6%, or 4% of sudden cardiac death into 2%. There’s of course, a value, but much bigger value is, can be, upfront predict patients who are of cardiac risk. And maybe those patients should not be treated with a BTK inhibitor at all. And so it was the point that I think we have the data with all the trials that we’ve done, both in study groups and in pharma. And we should take the effort and the time to invest, to really see maybe we should be learning, which patients are actually at risk. So, that was a very short summary of my iwCLL talk.

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Disclosures

Arnon Kater, MD, PhD, has participated in advisory boards and/or received research grants from Abbvie, BMS, Janssen, Roche/Genentech and Astra Zeneca; and has received speakers fees from Abbvie.

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