NEW YORK — Younger patients with polycythemia vera are often symptomatic and suffer impaired quality of life, reduced work productivity and excess mortality compared with age-matched controls, according to a new study.
“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,” explained Weill Cornell Medicine researchers. “The rationale for withholding cytoreductive therapy is data-sparse and driven by theoretical concerns for toxicity and unknown benefits from early treatment.”
In a recent report in Blood Advances, the researchers suggested there is some evidence that early treatment is “both well tolerated and potentially useful.” The authors cited a study showing that young patients receiving cytoreduction with ropeginterferon alfa-2b “experienced no more adverse events of grade 3 or higher than those randomized to treatment with phlebotomy alone, and improved quality of life, after 1-2 years of treatment.”1
Yet, they pointed out, cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) because of concerns that treatment toxicity might outweigh therapeutic benefits.
The authors argued, however, that no systematic data supports that approach. They embarked on a meta-analysis to provide an objective risk/benefit assessment of cytoreductive drugs in PV patients younger than 60 (PV60 or history of thrombosis). Their systematic review sought to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFNα) or hydroxyurea (HU).
To do that, the researchers searched PubMed, Scopus, Web of Science and Embase to identify 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis.
The weighted average age of 74 patients in 12 studies treated with rIFNα was 48 and for 1,397 in eight studies treated with HU was 56. The weighted average duration of treatment for either drug was 4.5 years. The study team determined that the pooled annual rate of discontinuation due to toxicity was 5.2% (n=587, CI 2.2%-8.2%) for patients receiving rIFNα and 3.6% (n=1097, CI 1%-6.2%) for HU.
The average complete hematologic response (CHR) for rIFNα and HU was 62% and 52%,
Respectively, they added, with patients experiencing thrombotic events at a pooled annual rate of 0.79% and 1.26%; sMF at 1.06% and 1.62%; AML at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively.
“No treatment-related deaths were reported,” the authors advised. “With acceptable rates of non-fatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFNα, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.”
- Chamseddine RS, Savenkov O, Rana ST, Khalid M, Silver RT, Kucine N, Scandura JM, Abu-Zeinah G. Cytoreductive therapy in younger adults with polycythemia vera: a meta-analysis of safety and outcomes. Blood Adv. 2024 Mar 20:bloodadvances.2023012459. doi: 10.1182/bloodadvances.2023012459. Epub ahead of print. PMID: 38507746.
