Ruxolitinib Offers Durable Hematocrit Control, Low Thrombosis Risk in PV


In an interview with Targeted Oncology, Aleksander L. Chojecki, MD, discussed findings from his research on hematocrit control and thrombotic risk in patients with polycythemia vera treated with ruxolitinib.

Blood cancer cells under the microscope close up macro: © stock_acc -

Blood cancer cells under the microscope close up macro: © stock_acc -

Treatment with ruxolitinib (Jakafi) remains an effective option in controlling hematocrit levels after 3 and 6 months and is associated with low thrombotic risk when given to patients with polycythemia vera (PV) in clinical practice.

A retrospective, observational, cohort study evaluated the use of ruxolitinib across 3 academic and regional practices in the US. A total of 69 patients with PV were enrolled and treated with ruxolitinib from December 2014 to December 2019.

At a median follow-up of 3.7 years (95% CI, 2.9-4.4), high rates of hematocrit control were observed, including in 88% of patients by 3 months and 89% of patients by 6 months. Additionally, no arterial thrombosis was observed.

Thrombotic events were observed in 3 patients, including 1 which was in the setting of a second malignancy, 1 which was post-operative, and another that was linked with prolonged immobility. Twenty-eight percent of patients started treatment with ruxolitinib due to poorly controlled platelet counts. Further, 46% of patients started therapy with ruxolitinib due to hydroxyurea intolerance.

In an interview with Targeted OncologyTM, Aleksander L. Chojecki, MD, Atrium Health, further discussed findings from his research on hematocrit control and thrombotic risk in patients with PV treated with ruxolitinib.

Targeted Oncology: Can you elaborate on the rationale behind this study?

Chojecki: We were interested in looking at the clinical work of ruxolitinib in the polycythemia vera population. There have been a lot of results in other clinical studies that select patient populations lead to the approval of medications. But clinical data tends to be a little bit different than a lot of more concise populations. We were looking, now that ruxolitinib has been available to patients for a number of years, at how it is being utilized only in clinical practice, ranging from larger tertiary centers to also more regional clinics and seeing how patients tolerated this and how clinicians were navigating and troubleshooting some of the [adverse] effects.

What were the methods and designs utilized in the study?

We wanted to get an in-depth look at the details of patients' tolerability, their response rates, their blood parameters prior to and at initiation, shortly thereafter, as well as several months after starting ruxolitinib. We designed that by looking at hematocrit parameters, particularly at onset, 1 month, and upwards of a year after. We also wanted to expand outside of the North Carolina/South Carolina area, so we included other centers, and we were happy to collaborate with Yale University in Connecticut and Kansas University in Kansas City.

The study reports high rates of hematocrit control with ruxolitinib. Could you discuss the significance of these findings in the management of polycythemia vera?

Currently, ruxolitinib has a label and is routinely used after intolerance to or refractoriness to hydroxyurea. Hydroxyurea tends to be the standard for many of these patients. But the field is now expanding, and there are a lot of new medications that are either in development or recently approved. Ruxolitinib has this second-line indication, and so the point of looking at the hematocrit control is to show that it is an effective medication. It is as effective, if not more effective than some of the data that led to its approval, and that it is safe to use. Oftentimes, it can be difficult for patients to learn of their intolerance to first-line medication, or it is not working for whatever reasons. To know that there is a very effective medication in the second-line, I think, is reassuring to patients and clinicians.

What challenges did you encounter while collecting and analyzing data on the study?

There are many limitations to our study. First, there was a retrospective design, so there is always a bias associated with that. But furthermore, when collecting records from other medical centers, oftentimes we struggle with limited or incomplete datasets. When we did our analysis, we did have a few incomplete charts that we were not able to gather the full scope.

There was arterial thrombosis among patients who received ruxolitinib in the study. Could you discuss the implications of these findings in terms of the thrombotic risk management in these patients?

That is important and there is recent data that was presented, confirming this about a year or 2 ago as well. It is known that patients with polycythemia vera have a higher rate of thrombotic events, including arterial, and aside from heavy cardiovascular risk factors, hematocrit control is important. But even by nature of having a driver mutation such as JAK2, that puts patients at a higher risk. This medication, even though there was a smaller patient population, we had very low rates of arterial thrombosis, which complements a lot of the data that has been already published.

Can you explain why some patients with PV may be intolerant to hydroxyurea, and how ruxolitinib addresses this issue?

Intolerance can mean a few things for patients. Hydroxyurea has been around for quite some time, and it is pretty well known to many clinicians. But oftentimes, patients may have a range of symptoms. Oftentimes, diarrhea can be encountered, or sometimes it may cause cytopenias. That limits the clinician's ability to effectively manage the patient. When we are running into difficulties with tolerance issues, whether it is a patient not being able to tolerate the medication, whether it is diarrhea, nausea, [gastrointestinal] upset, etc, this medication seemed to have a good place in the line of treatments, and is well tolerated and minimizes some of those [adverse] effects that we are seeing with hydroxyurea.

The same is true for refractoriness. Some patients may be on high doses of hydroxyurea, and it is still not controlling their hematocrit, or they develop lower white blood cells or lower platelets, effectively limiting the clinician's ability to titrate hydroxyurea. So again, this medication serves a good purpose.

What factors should clinicians consider when deciding to switch patients with PV to ruxolitinib?

We made mention that a year a frequently cited reason why patients were switched to ruxolitinib was due to uncontrolled platelet counts. That is not something that is routinely reported. I think there is limited data with that. We found that to be interesting. What factors? Well, it is difficult for me to say, because we do not have enough data about us. That is something that I think does warrant further research and explanation. We do know that patients with polycythemia vera may have some overlapping features with elevated platelets as well. I think it would be important to know whether the elevated platelets are due to the [myeloproliferative neoplasm (MPN)]. Sometimes it could also be from iron deficiency from phlebotomy. Trying to iron out what the cause of the elevated platelets are, but with the current level of data, it is not something that I think is a standard of care as to transition the patients from hydroxyurea to ruxolitinib due to elevated platelets against something that we found. But that does warrant further exploration.

Could you discuss the safety profile of ruxolitinib observed in this study?

We found that it was relatively safe. Ruxolitinib has been on the market for more than 10 years. I think most clinicians are familiar with the safety profile. Some of the [adverse] effects that we saw, which has commonly been reported, were weight gain, sometimes headaches, nausea, edema, fatigue, and headaches. Many of these [adverse] effects were minimal and led to discontinuation of ruxolitinib.

What implications do you think these findings have on the future management of patients with PV?

I think the data supports the use of ruxolitinib in patients with polycythemia vera. It is safe and is effective. There are copious amounts of data out there confirming this. I think this study just adds more information in the clinical contexts, outside from large tertiary centers and regional sites as well, just adding more information that this medication is safe, effective, and well-tolerated.

Are there any other areas for future research that you believe are particularly important based on these results?

I do think the use of ruxolitinib in patients with elevated platelets is interesting. I do think that would warrant more investigation and research. Also, the financial impact is something that we did not look into, but this medication tends to be a little bit more expensive. Knowing how patients are able to afford this, and this is an evolving area of research within the field as just in general costs are becoming more of an issue and challenge for patient care.

  1. Chojecki A, Boselli D, Dortilus A, et al. Hematocrit control and thrombotic risk in patients with polycythemia vera treated with ruxolitinib in clinical practice. Ann Hematol. Published online April 25, 2024. doi:10.1007/s00277-024-05735-7
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