Real-world treatment patterns and clinical outcomes in patients with essential thrombocythemia treated with cytoreductive therapy: A retrospective analysis of electronic health records data

Abstract Background: Essential thrombocythemia (ET) is a rare, chronic myeloproliferative neoplasm characterized by sustained thrombocytosis, risk of thrombosis and bleeding, and progression to post-ET myelofibrosis (MF) or blast-phase disease. Cytoreductive therapy is recommended for thrombosis prevention in high-risk or symptomatic patients, but despite standard of care (SOC) therapies, many ET patients continue to experience disease complications, inadequate symptom control and suboptimal outcomes. Contemporary real-world studies are needed to evaluate disease burden and unmet treatment needs in ET. Aims: To characterize the treatment landscape and clinical outcomes among patients with ET treated with cytoreductive therapy in the U.S. Methods: Adult patients who met the following inclusion criteria were identified from the Mass General Brigham Research Patient Data Registry between January 1, 2012 and September 5, 2024: 1) an ET diagnosis code (by ICD10) associated with a hematologist/oncologist visit (i.e., first ET diagnosis); 2) a subsequent physician visit with an associated ET diagnosis code; 3) elevated platelet count (≥450x109/L) in the 6-months prior to first ET diagnosis; and (4) prescription for a SOC cytoreductive therapy on or after the first ET diagnosis. The prescription date of the first-observed cytoreductive agent (i.e., first-line [1L] therapy) was defined as the index date. 1L treatment discontinuation was defined as a switch to a different 2L therapy, or as a gap of >60 days following the end of 1L therapy unless a subsequent prescription of the same agent was observed after the 60 day gap (defined as treatment interruption). Clinical outcomes including thrombotic events and major bleeding events were summarized from the index date to the earliest of 1L treatment discontinuation, progression to MF or blast phase disease, or end of follow-up. Blast phase disease was defined by ≥1 acute myeloid leukemia diagnosis code. Major bleeding events were defined using modified ISTH criteria including those occurring in a critical area or organ in an inpatient setting, fatal bleeding (defined as bleeding in a critical area or organ preceding death by ≤45 days), or symptomatic bleeding (defined as bleeding leading to a drop in hemoglobin ≥2g/dL or red blood cell transfusion within 48 hours). Results: Among 673 patients who met the inclusion criteria, median (range) age at the index date was 70 (20 - 96) years, 67.3% were female, 88.0% were white. 14.1% had a history of thrombosis in the 6-months prior to 1L initiation. The mean (SD) follow-up time was 41.0 (31.3) months. The most common 1L treatment was hydroxyurea (94.1%); use of other treatments (e.g., interferon alfa [1.8%], ruxolitinib [1.5%], anagrelide [1.3%], and busulfan [0.3%]) was rare. 1L treatment modifications occurred frequently: 235 patients (34.9%) experienced treatment interruptions and 131 (19.5%) discontinued treatment. Among those who discontinued, median (interquartile range) time from 1L initiation to discontinuation was 14.1 (5.1 – 36.6) months; of these, 75 (57.3%) received no further treatment during our follow-up. Among all 1L treated patients, 56 (8.3%) switched to 2L therapy. Overall, 30.5% of patients experienced ≥1 ET-related complication after the index date, including thrombotic events (23.2%), major bleeding events (3.6%), and progression to MF (4.9%) or blast phase disease (2.1%). Sixty-six patients (9.8%) died of any cause. Among patients with available labs, 65.6% (368/561) of patients had an average platelet count ≥600 x 109/L in the first 6 months post-index, and 30.1% (137/455) during months 6-12. Conclusions: Despite SOC treatment with cytoreductive therapy, a significant proportion (30.5%) of ET patients experienced disease-related complications including thrombosis, disease progression, and major bleeding. These complications may be due in part to frequent therapy interruption or discontinuation (47.7% of patients), underscoring the limitations of SOC ET therapy. Our findings highlight ongoing challenges in ET management and the need for alternative therapeutic strategies to improve long-term outcomes in ET.