ADVERTISEMENT
How to Determine When First-Line Therapy for Polycythemia Vera is Failing
Expert Roundtable Part 3
Expert Roundtable Part 3
In this expert roundtable series, Claire Harrison, MD, Guy's and St Thomas' NHS Foundation Trust leads a 4-part roundtable panel discussion on polycythemia vera (PV) and the importance of hematocrit control with Jean-Jacques Kiladjian, MD, Saint Louis Hospital, Paris, and Alessandro Rambaldi, MD, University of Milan.
In the third video of the series, the members of the panel discuss how to determine when first-line PV therapy is failing.
Transcript:
Claire Harrison: Welcome everyone and thank you for joining us today for our third discussion, where we'll be covering the topic of how we know when therapy is failing and what treatment to choose next for our patients with PV.
Maybe I could come to you, Alessandro, and just ask you to touch on actually what the targets are for treating a patient. Do you aim to completely normalize the blood count? Are there times when you might use a different target? Let's start with that.
Alessandro Rambaldi: Well, I think that the aim to normalize the blood counts is important, is not an absolute aim of our treatment, but is important. The aim particularly in that respect is to improve the quality of life of the patients, and if we can reduce or abrogate the need to perform phlebotomies, that is something that most patients really appreciate.
The second point is the impact on the symptoms that the patient can have. So, failing in achieving phlebotomy independence and failing in controlling the symptoms, in particularly the pruritus, is something that should be considered of paramount importance when a pharmacological treatment has been initiated.
Claire Harrison: Yeah, I think that's important. So you're touching on also the low-risk patients when their current therapy is failing, as well as the higher-risk patients when maybe interferon or hydroxy is failing.
You are also touching on the fact that it's important that not only do we measure the blood count, but we also look at: are they needing a venesection? How often are they needing it? Iron deficiency can be a big issue for these patients. But also, what's the thermometer like for their symptoms, or how is their quality of life impacted? These are all really important things.
Alessandro Rambaldi: Absolutely.
Claire Harrison: So Jean-Jacques, do you aim to get the white count less than 10 and the platelets less than 400, or are you just content with nearly there? Maybe you could comment.
Jean-Jacques Kiladjian: That's a very important question. As Alessandro said, the main aim is clearly the hematocrit first, below 45. This was established by the cyto PV study and I think we should always target that. And then, should we normalize completely the leukocytes, the platelets? We have no, to my knowledge, evidence that the platelet count is really important, except if it's extremely elevated above 1 million or 1.5 million, because then you have a risk of bleeding.
But otherwise, in PV it has never been shown to be clearly associated to an increased risk, so maybe we can be more flexible with the platelets. And about leukocytes, we discussed already this in the risk stratification. I think it's an important parameter that has a lot of implications, and recently the European LeukemiaNet Group, for example, updated the management guidelines for PV and proposed that having more than 15,000 leukocytes or 20,000 leukocytes was not good, and should prompt to start a cytoreductive treatment, for example, then aiming to reduce the leukocyte count.
So I think, yes, this can be also an important target. And of course, last but not least, the symptoms. If you have normalized blood counts but your patients still suffer 1 symptom or several symptoms, like pruritus, but sometimes others, fatigue, et cetera—it's also maybe a failure. Something new also by the ELN, I would be happy to have your comments on that, is if your patient has completely normal counts, doesn't suffer from symptoms, but then has a thrombotic event, is it a reason to say that your treatment failed, and should it be a reason to switch therapy?
Claire Harrison: Well, I think you raise a really important point there. So for me it would really depend on the patient in front of me. We spent a while in an earlier session discussing about vascular risk, so for me, I'm not really treating a patient if I don't tell them to stop smoking, lose weight, watch their blood pressure, et cetera. So if the patient has no other vascular risk apart from their PV and has a thrombosis, then for me, I'm not sure I would change a therapy, but I might intensify a therapy, talk a bit about antiplatelet therapy, whether that needs to be intensified a bit as well. I think these things all need careful looking at.
Fortunately, it's quite uncommon for a patient who's on therapy to have an event. Usually there might be a trigger like surgery or something like this, but I'm not sure I would definitely change. And then I'm also intrigued and remember your comment about the white cell count, so more than 15 or more than 20, but then so you start a treatment, and then is it what, less than 10?
Jean-Jacques Kiladjian: Probably.
Claire Harrison: Yeah.
Jean-Jacques Kiladjian: It would be to normalize, at least bring back to normal.
Claire Harrison: Yeah. I think that's really important. So then lastly, you are treating a patient, Alessandro, and you've been treating them for a while, but how long do you want to persevere with the treatment?
So we know interferon for a while, it's really important to be patient and not to—we have a British saying, “not throw the baby out with the bath water”—so you don't want to stop it too soon, because you can see that actually if you'll wait a while, it can be good for your patient.
So, how long would you generally use a treatment for? Intolerance is different, but not achieving where you want to go on a good dose, how long would you wait?
Alessandro Rambaldi: I think it depends on the patient's need. I mean in what sense, in which sense the patient is fading or is not yet responding to the treatment, and what are the needs of that specific patient? It depends on the age of the patient.
Because for example, if you treat a young patient with interferon, I would spend some time and be patient as long as I can to achieve the treatment results that you hope to get. It's probably different from an older patient, in which the aim of treatment may be different.
Claire Harrison: Yeah. I think that's true. I think older patients are really important. We focus a lot on younger patients, but many of our patients are elderly and they often take a lot of medications, so we do need to be cautious. So for me, if my patient's still needing the occasional venesection, I'm not sure I would stop it if they're otherwise tolerating a treatment really well.
Alessandro Rambaldi: I totally agree on that. I totally agree. It depends on the number of venesections you need and whether they are really impacting the quality of life of the patient.
Claire Harrison: And then I suppose we must really talk about intolerance to treatment, so intolerance for hydroxyurea, hydroxycarbamide. Might be skin cancer, mouth ulceration, leg ulceration.These are very difficult, often occurring again in elderly patients, usually need to have cessation of treatment to heal.
But let's hear from you, Jean-Jacques, about intolerance to interfere in a couple of minutes maybe, and how you manage that, please.
Jean-Jacques Kiladjian: Yes, sure. In my experience, intolerance to interferon occurs early, usually within the first months of therapy, and once you pass 6 to 12 months, you don't see a lot of intolerance, except maybe for immunity problems because sometimes we regularly follow autoimmune antibodies in these patients. There's no guidelines, but I look at them at least every 6 months as, for example, for those who have antinuclear antibodies.
That is quite frequent, especially in younger females at baseline, and just check if they don't go up with the treatment. So, this may happen late, but otherwise let's say the clinical intolerance or the hepatic intolerance, sometimes you see an increase in transaminases and liver enzymes. That occurs usually at the beginning of the treatment. I would say that within the first 3 to 6 [months], usually you see if there's an intolerance or not.
Claire Harrison: Well, I'm learning so much from talking to you today and I want to thank you for joining us for this discussion on how we know treatment is failing.
Well, that's going to come in our next session, so please join us for that, which will be when we might choose ruxolitinib or when we might choose to switch between interferon and hydroxycarbamide. Thank you so much.
