Therapeutic Phlebotomy, Hydroxyurea Improve Overall Survival in Geriatric Polycythemia Vera

Treatments with therapeutic phlebotomy and hydroxyurea (HU) are associated with improved overall survival (OS) and decreased risk of thrombosis in older patients with polycythemia vera (PV), according to a recent retrospective cohort study published in Blood Advances.¹

PV, a myeloproliferative neoplasm with a median age at diagnosis of 65 years, is associated with reduced OS and is characterized by an increased risk of thrombosis. Although current guidelines recommend therapeutic phlebotomy to maintain hematocrit below 45% for all patients with PV and additional cytoreductive therapy (such as HU or interferon, which can directly reduce counts of red cells, white cells, and platelets) for high-risk patients with PV,² little has been known about the impact of these therapies in the real-world treatment setting. In addition, the study’s authors, led by Nikolai A. Podoltsev, MD, PhD, of Yale University, concluded that phlebotomy and HU were underused in their sample of older PV patients.

The researchers used data from the National Cancer Institute and the Centers for Medicare and Medicaid Services’ Surveillance, Epidemiology, and End Results (SEER)-Medicare database of older adults (median age, 77 years) diagnosed with PV from 2007 to 2013. A total of 820 patients with PV (57% were women, 91.2% were white) met the inclusion criteria.

In the study group, 16.3% of patients received neither phlebotomy nor HU, 23% were managed with phlebotomy alone, 19.6% with HU only, and 41.1% were managed with both treatments. On average, phlebotomy users had a median of 7.0 phlebotomies (interquartile range [IQR], 3.0-12.0) from diagnosis to end of follow up, and their median phlebotomy intensity (number of phlebotomies per year) was 2.3 (IQR, 1.1-4.1). The median HU proportion of days covered (PDC) was 61.6% (IQR, 35.2%-80.1%). After a median follow up of 2.83 years, 37.2% (n = 305) of patients died.

Statistical methods were used to assess the effect of phlebotomy and HU on OS and the occurrence of thrombotic events. Phlebotomy (yes/no; hazard ratio [HR] = 0.65; 95% confidence interval [CI], 0.51-0.81; P <.01), increasing phlebotomy intensity (HR = 0.71; 95% CI, 0.65-0.79; P <.01), and a higher PDC by HU were all significantly associated with lower mortality. When thrombosis was the outcome of interest, phlebotomy (yes/no; HR = 0.52; 95% CI, 0.42-0.66; P <.01) and increasing phlebotomy intensity (HR = 0.46; 95% CI, 0.29-0.74; P <.01) were significantly associated with a lower risk of thrombotic events, as was a higher HU PDC.

Median survival was 6.29 years for phlebotomy users and 4.50 years for phlebotomy nonusers (log-rank test, P <.01). The median survival for HU users was 6.02 years and 5.25 years for HU nonusers (log-rank test, P <.01). The researchers note that both treatment modalities were underused in this population of older patients. Only 64.0% underwent therapeutic phlebotomy, and 60.6% received HU. Because of the small sample size, the researchers were not able to compare patients who used phlebotomy and HU concurrently with those who used these 2 treatments sequentially.

“These findings suggest that patients in our study cohort were undertreated according to European Leukemia Net (ELN) and National Comprehensive Cancer Network (NCCN) guidelines,” they state. “Improved dissemination and implementation of the guidelines may translate to better patient outcomes.”

References

1. Podoltsev NA, Zhu M, Zeidan AM, et al. The impact of phlebotomy and hydroxyurea on survival and risk of thrombosis among older patients with polycythemia vera. Blood Advances. 2018;2:2681-2690. doi: 10.1182/bloodadvances.2018021436.
2. Mesa RA. New guidelines from the NCCN for polycythemia vera. Clin Adv Hematol Oncol. 2017;15:848-850.