Pooled Analysis Shows Cytoreduction to Be Safe, Tolerable in Younger Patients With PV

Ashling Wahner

Cytoreductive therapy with interferon alfa (rIFNα) or hydroxyurea is safe and well tolerated in patients with polycythemia vera (PV) under the age of 60 years and induces annualized discontinuation rates comparable to those reported with these agents in older patients with PV, for whom cytoreductive therapy is routinely used, according to findings from a meta-analysis that were published in Blood Advances.1

Across the 14 studies included in this analysis, rIFNα discontinuation rates ranged from 4.6% to 37% over median durations of 0.4 to 6.3 years. Hydroxyurea discontinuation rates ranged from 2.6% to 17% over median durations of 0.5 to 14 years.

Although the use of cytoreductive agents, such as rIFNα and hydroxyurea, is associated with reduced thrombosis risk in PV, these agents are not routinely recommended by the European LeukemiaNet (ELN) or the National Comprehensive Cancer Network (NCCN) for patients with PV under the age of 60 years. The ELN recommends cytoreductive therapy for patients with PV who are younger than 60 years of age and have not had prior thrombotic events provided that they have strictly defined phlebotomy intolerance, symptomatic progressive splenomegaly, persistent or progressive leukocytosis, extreme thrombocytosis, persistently high cardiovascular risk, inadequate hematocrit control requiring phlebotomies, and/or persistently high symptom burden.2 The NCCN does not recommend cytoreductive therapy as initial treatment for patients with low-risk disease.3

“Unfortunately, effective and potentially life-prolonging cytoreductive therapy is often deferred in younger patients who are considered ‘low-risk’ because of their age and lack of thrombosis history,” senior study author Ghaith Abu-Zeinah, MD, an instructor in medicine at Weill Cornell Medical College and an assistant attending physician at the NewYork Presbyterian Hospital in New York, New York, and coauthors, wrote in the paper.1 “The rationale for withholding cytoreductive therapy is data-sparse and driven by theoretical concerns for toxicity and unknown benefits from early treatment. Yet, there is some evidence that early treatment is both well tolerated and potentially useful.”

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Younger Patients With PV May Benefit From Earlier Treatment With Cytoreductive Therapies

Laura Joszt, MA

Although patients younger than age 60 with polycythemia vera (PV) are typically not treated with cytoreductive therapy due to treatment toxicity concerns, this may result in an undertreatment of patients as there is no clear evidence that the risk of toxicity exceeds the potential benefit of treatment, according to a study published in Blood Advances.1

PV causes an overproduction of blood cells in the bone marrow, which leads to high numbers of circulating red blood cells.2 This thickens the blood, which may not flow through smaller blood vessels properly. Although PV can be diagnosed at any age, it most often occurs in people over the age of 60 years.2

For most patients, phlebotomy is the standard treatment, and it may be the only treatment needed for years. However, additional treatment to suppress the formation of blood cells in the bone marrow may be needed. Cytoreductive therapies, such as interferons, hydroxyurea, ruxolitinib, and anagrelide, may be needed, particularly for high-risk patients.3

Currently, cytoreductive therapies are not routinely recommended by the European LeukemiaNet or National Comprehensive Cancer Network for patients with PV younger than 60 years who don’t have a history of thrombosis, a high symptom burden, or an intolerance to phlebotomy.

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Navigating Cytoreduction in MPNs: Benefits, Risks, and Considerations

Jordyn Sava

In an interview with Targeted Oncology, Douglas Tremblay, MD, discussed the significance of cytoreductive therapy in mitigating thrombotic risk in myeloproliferative neoplasms.

According to Douglas Tremblay, MD, cytoreductive therapy has emerged with a pivotal role in mitigating thrombotic risk in the treatment landscape of myeloproliferative neoplasms (MPNs), specifically essential thrombocytopenia (ET) and polycythemia vera (PV).

Despite the evident benefits, each therapy carries unique adverse effects, requiring the careful consideration of patient-specific factors in treatment administration. Deciding when to initiate cytoreductive therapy in patients with chronic MPNs relies on accurate risk assessment, with parameters such as age and prior thrombotic events often guiding treatment decisions.

Frontline therapies, such as hydroxyurea and interferon, manage blood counts for patients with ET and PV, and newer options are emerging, according to Tremblay, assistant professor of medicine at the Icahn School of Medicine at Mount Sinai. However, the long-term implications focus on thrombosis prevention and disease progression.

Ongoing research endeavors aim to delve deeper into surrogate end points and novel therapeutic avenues, promising to further refine and revolutionize the management of MPNs.

In an interview with Targeted OncologyTM, Tremblay discussed the significance of cytoreductive therapy in mitigating thrombotic risk in MPNs, specifically ET and PV.

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