Myeloproliferative Neoplasms - Episode 13
Srdan Verstovsek, MD, PhD: So, we are moving from looking at the hematocrit control alone, to controlling the white cell platelet symptoms and the spleen. Rami, in your hands, if those factors are not controlled well, and certainly you would like to primarily have control of hematocrit and then the white cells and the spleen and the symptoms and the platelets, perhaps then there would be a number of cases where you are unable to control the 5 factors that I mentioned, with hydroxyurea alone. Therefore, there is room for more therapies, and the targeted therapy that we’re talking about here is ruxolitinib. It seems that it’s very valuable in the second-line setting. We have 60% normalization of the hematocrit, we have about 25% of the patients controlling all blood cell counts and it’s very durable. I think durability is particularly impressive to me. What’s your take on the utility of ruxolitinib in the second-line setting?
Rami Komrakji, MD: I totally agree. Obviously, as Andrew mentioned, we are looking at different dimensions. We are looking at the long-term disease outcome, short-term outcome. Most of those patients have a good prognosis when we’re looking at either thromboembolicevents as well as the symptoms. We typically don’t think of p vera [polycythemia vera], that patients are symptomatic, but when you start talking to patients and listening, many of them had itching, that sometimes can interfere with activities, fatigue, some of them will have symptoms from the spleen, vasomotor symptoms. Hydrea sometimes will not do a great job controlling those aspects, even if the hematocrit is better controlled.
The other thing I always talk about is basically when we think about phlebotomies and what is acceptable and how often should we do phlebotomies on those patients. Is it really acceptable that we are doing a phlebotomy every month on those patients? Although there may not be evidence that phlebotomy per se is harmful, but I think a patient who requires phlebotomies on a regular basis has inadequate disease control or a disease that’s really active, that we may need to think of changing therapy based on that. The other thing, it also depends how often do you look. If we are seeing those patients and we are just checking hematocrit levels every 4 months, sometimes in between we don’t know how long they are staying about that target of 45 that we aim for. So, maybe sometimes we are also looking more often.
I think ruxolitinib offers a great option of controlling disease for patients who are sometimes difficult to control with Hydrea, especially when you start going on the higher doses. In my experience, toxicity with Hydrea starts to become very prominent when the dose is more than 2 grams per day. Patients will have nausea, sometimes sores, and you start seeing more myelosuppression with the treatment. If patients have symptoms, especially on a higher dose, if they are still requiring phlebotomies, if I’m not able to maintain their hematocrit in that range below 45 on a regular basis, for those particularly that have drenching night sweats, fevers, and itching, I find ruxolitinib as a very useful option for patients.
Srdan Verstovsek, MD, PhD: Let me ask Andrew 1 more question about the other side of the coin. We briefly talked about herpetic infections and squamous cell carcinoma of the skin. Is there a main concern here, or we are able to control those by perhaps monitoring patients’ skin and providing perhaps advice on the management of herpetic infections? Briefly.
Andrew Kuykendall, MD: I think these are the main adverse effects that we talk to patients about, that I think are concerning—certainly, the shingles reactivations and the nonmelanoma skin cancers. Recently, there was a presentation that suggested that the patients who were at a higher risk for these non-melanoma skin cancers were patients that had previous nonmelanoma skin cancers. I think that helps to certainly identify patients who are at higher risk, and often those patients already have dermatologists and we can counsel them to see their dermatologists more frequently to be able to prevent these things from occurring. As far as the herpetic and shingles infections, we’re not really sure how the new shingles vaccine affects that, but certainly it’s something that’s recommended from our standpoint. It’s not a live virus vaccine, and it has shown efficacy that’s preferable to the prior shingles vaccine.
But what I counsel patients on, oftentimes this is a group of patients 65 years and older, they’re at risk for shingles reactivations already, and shingles reactivations can be something that when managed early in the course of the disease, some of the problematic symptoms can be mitigated. Sometimes, the trouble is not recognizing this. So if counseling patients, they can become more aware of this and hopefully present to medical care earlier on in the process.
Srdan Verstovsek, MD, PhD: I agree. So, we balance here with the occasional adverse effects that you mentioned by carefully monitoring patients, but we count on a tremendous improvement not only in blood cell count, but in quality of life with ruxolitinib, and perhaps even improvement in the iron levels, eliminating that possible adverse effect or otherwise problematic issue in some of the patients. So, I thank you all very much for this lively discussion. We’re going to conclude this case and move on to the next one.
Transcript edited for clarity.