Treating Low-Risk Polycythemia Vera in the Second Line

Polycythemia vera (PV), a chronic myeloproliferative neoplasm, has a handful of potential treatments for first and second-line therapy. At a live event in Philadelphia, Pennsylvania, Raajit K. Rampal, MD, PhD, director of the Center for Hematologic Malignancies and the Myeloproliferative Neoplasms Program at Memorial Sloan Kettering Cancer Center, discussed some options for a patient with low-risk PV. He detailed the initial management with phlebotomy and aspirin and then analyzed some of the data supporting the efficacy of ropeginterferon alfa-2b (Besremi).

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CASE SUMMARY

Patient profile

• 42-year-old woman
• Asymptomatic at diagnosis
• Regular physical activity
• Body mass index: 23.4 kg/m²
• No significant medical history
• Abnormal blood at work at annual physical

Initial labs

• Hematocrit: 52%
• Hemoglobin: 17.2 g/dL
• White blood cell count: 9.8 x 10⁹/ L
• Platelets: 450 x 10⁹/ L
• Erythropoietin: 3 mU/mL (low)
• JAK2 V617F: Positive

Risk assessment

• Low-risk category
• Age under 60 years
• No prior thrombosis

Initial management

• Phlebotomy (target hematocrit <45%)
• Aspirin 81 mg per day
• Cardiovascular risk factor management
• Monitor for progression

Targeted Oncology: What do you think of the initial treatment for this patient with PV?

Raajit K. Rampal, MD, PhD: There is a good benefit to aspirin [in PV].¹ You don't have to use anything more than 81 mg a day. For anticoagulation, what do you do in a patient who's had deep vein thrombosis? Should they stay on aspirin and rivaroxaban? Is that a good idea? There aren't a lot of data to guide you here, but there is 1 paper that has shown…that patients, especially those over the age of 65, have a higher risk of bleeding with the combination of the 2 agents vs using 1 alone.² The recommendation that we've been following is if they have a clot and they're 65 years or older or have some other predisposition to falling or something else, we usually will just go with 1 agent—usually the anticoagulant and stop the aspirin. In the younger patients, we tend to still do both.

What do the NCCN guidelines recommend for this patient population?

In terms of NCCN guidelines, for low-risk patients, there's monitoring, there's assessment for disease progression, but there's also symptomatic monitoring. For those patients, it is a reasonable thing to think about starting cytoreductive therapy in a symptomatic young patient. There are some data that I think may challenge this notion and maybe suggest that earlier intervention might be the right thing for most patients. It suggests [but] does not tell us that that's what we should be doing.

What do you think of using ropeginterferon alfa-2b for this patient after aspirin? How does tolerance to this drug affect treatment dosage?

There is a package insert with ropeginterferon which talks about dose escalation. But we have many patients who do fine at 100 µg every 2 weeks. They don't need to be escalated to 250 µg or anything higher. It just takes time; that's the only thing, is that sometimes you do have to continue phlebotomy for 3 to 4 months before you get into a steady state, just because of the kinetics. But lower doses can be effective for sure.

What data showed efficacy for this drug in patients with low-risk PV?

There was a nice study for low-risk PV [Low-PV; NCT03003325]. All patients were aged 18 to 60 who had low-risk PV, and they were randomly assigned to get treated with ropeginterferon plus standard of care, which was phlebotomy and aspirin, or they were randomly assigned to do phlebotomy and aspirin. The primary end point was the percentage of patients maintaining the hematocrit less than 45 over 12 months without evidence of disease progression. Secondary end points were hematologic response, reduction of splenomegaly, and JAK2 allele burden.³

What was the design and outcome of the Low-PV trial?

At 12 months, the composite end point was hit by a significantly higher percentage of patients treated with ropeginterferon; there was better hematocrit control. But the thing that was quite interesting was that there was more disease progression, even in a short period of time, in the patients who got standard therapy. Part of the definition of disease progression was an increase in the platelet count, which I think we could debate whether that's really a progression event.

But these data got the trial stopped by the data safety monitoring committee because they said it wasn't applicable to continue given this progression risk [in the standard-of- care arm and efficacy in the ropeginterferon arm]. The problem is, you have very interesting data in a low-risk population, but now the trial is stopped. Sixty or so patients were accrued per each arm. The phlebotomy needs were lower in the patients who got ropeginterferon, and the ferritin levels increased in the patients who got ropeginterferon, because they weren't getting phlebotomized.

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DISCLOSURES: Rampal has previously reported professional services and activities with AbbVie, American Society of Hematology, Boxer Capital, LLC, Chinese Academy of Medical Sciences, Cogent Biosciences, Inc., CTI BioPharma Corp., GlaxoSmithKline, Incyte, Jubilant Therapeutics Inc., MorphoSys AG, MPN Research Foundation, Noble Insights, PharmaEssentia, Protagonist Therapeutics, Inc., and Sumitomo Pharma.

REFERENCES:

1. Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004;350(2):114-124. doi:10.1056/NEJMoa035572

2. Zhang Q, Ding Q, Yan S, Yue QY. Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase. Eur J Clin Pharmacol. 2022;78(9):1521-1526. doi:10.1007/s00228-022-03357-4

3. Barbui T, Vannucchi AM, De Stefano V, et al. Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial. Lancet Haematol. 2021;8(3):e175-e184. doi:10.1016/S2352-3026(20)30373-2