Real-World Patterns of First-Line Hydroxyurea Treatment Among Patients with Essential Thrombocythemia in US Community Oncology Practices

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by excessive clonal platelet production. Hydroxyurea (HU) is the recommended first-line cytoreductive treatment for ET. The objective of this study was to describe first-line HU treatment patterns and discontinuation among patients with ET in real-world US clinical practices.

Methods: Data were extracted from medical charts of patients with an ET diagnosis who received cytoreductive therapy at community oncology/hematology clinics between June 1, 2011, and September 15, 2016 (study period). Demographics, clinical characteristics (ie, blood counts, symptoms, thrombotic events), and HU treatment patterns were evaluated. Data on HU treatment patterns included start date, signs/symptoms at treatment start, starting dose, dose change, most stable (longest duration) dose, and reasons for discontinuation. Kaplan-Meier estimates of HU discontinuation rates over time were reported.

Results: 755 patients from 50 oncology/hematology practices who had HU as first-line cytoreductive therapy were included in this study. Most (65.4%) of the patients were diagnosed within the 3 years preceding the end of study period (ie, September 15, 2016). Mean (SD) age was 68.6 (11.5) years; 50.9% of patients were female. The median time from diagnosis to HU initiation was 0.3 months, and from HU initiation to the end-of-study follow-up (the most recent visit) was 20.2 months. The most frequent signs and symptoms at HU initiation were fatigue (48.6%), headache (16.0%), and splenomegaly (12.7%). The median duration of HU was 18.6 months, with 81.1% still on HU at the end of study period. The mean (SD) starting dose and stable dose were 1024.2 (522.3) mg/d and 1388.9 (726.5) mg/d, respectively. Only a small proportion (17.8%) of patients received HU doses >2000 mg/d. At the most recent visit, 27.6% of HU users had ≥1 ET symptom, with 20.3% reporting fatigue; 36.8% and 9.0% of patients had platelet counts ≥400 × 10⁹/L and white blood cell (WBC) counts ≥10 × 10⁹/L, respectively. 33 patients (4.4%) had died by the end of study period, with heart attack (n=10 [30.3%]) and hematologic malignancy (n=9 [27.3%]) being the most common causes of death.

82 patients (10.9%) discontinued first-line HU treatment during the median follow-up of 20.2 months from HU initiation. Kaplan-Meier estimates of 1-, 3-, and 5-year discontinuation rates were 5.8%, 14.5%, and 20.7%, respectively. Among patients who discontinued, the median duration of HU treatment was 13.1 months. The most common physician-reported reasons for HU discontinuation were intolerance (35.4%), resistance (23.8%), progression to acute myeloid leukemia (9.8%), and progression to myelofibrosis (7.3%). At the most recent visit, 48.8% of patients who discontinued HU had ≥1 ET symptom; 51.9% and 33.8% had platelet counts ≥400 × 10⁹/L and WBC counts ≥10 × 10⁹/L, respectively; and 6.1% had ≥1 thrombotic event. In contrast, 25.0% of patients who continued HU had ≥1 ET symptom, with 18.7% reporting fatigue; 35.5% and 12.9% of patients had platelet counts ≥400 × 10⁹/L and WBC counts ≥10 × 10⁹/L, respectively. Upon HU discontinuation, 3.6% reinitiated HU at a later time, 36.6% used another cytoreductive therapy (anagrelide or ruxolitinib), and 59.8% did not receive any further treatment.

Conclusions: The HU discontinuation rate among patients with ET increased over time, with a rate of 14.5% at 3 years. Intolerance or resistance were the primary reported reasons for discontinuation of HU. Almost two-thirds of patients with ET did not receive further treatment after HU discontinuation. A substantial proportion of patients who continued HU treatment still had elevated blood counts and symptoms. These patients may benefit from alternative management strategies.