Clinical Characteristics and Treatment Patterns By Risk Stratification in Patients with Essential Thrombocythemia: An Analysis of the MOST Study

Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm (MPN) characterized by thrombocytosis and increased risk of thrombotic events and hemorrhage. Treatment of ET is risk-adapted, focused on preventing thrombosis, bleeding, and minimizing symptoms. Real-world data regarding factors contributing to treatment initiation and therapy choice in this setting are limited. Here, we present the clinical characteristics of low- and high-risk pts with ET enrolled in Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) and assess whether these differ for pts who were treated vs untreated at the time of enrollment.

Methods: MOST (NCT02953704) is an ongoing multicenter, non-interventional, longitudinal, prospective, observational study in pts with specific risk categories of ET or MF. Pts included in this analysis met modified ELN criteria (J Clin Oncol. 2011;29:761) for high-risk ET (age ≥60 y and/or thromboembolic event [TE] history) or low-risk ET if receiving ET-directed therapy (not including aspirin only). Data from pt records were entered into an electronic case report form during usual-care visits over a planned observation period of 36 months. Patient-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics.

Results: Of 1235 pts with ET enrolled at 124 sites between 11/29/2016 and 12/31/2018, 1210 were included in the analysis; 25 were excluded (low-risk receiving aspirin alone [n=16]; low risk receiving neither ET-directed therapy nor aspirin [n=8]; BCR-ABL mutation-positive [n=1]). Of the 1210 pts analyzed, 159 (13.1%) were low-risk (all treated), 887 (73.3%) were high-risk and treated, and 164 (13.6%) were high-risk and untreated, respectively. Reasons for high-risk categorization were similar for treated and untreated high-risk pts (age ≥60 y, 67.5% vs 70.1%; TE history, 8.8% vs 10.4%; both age ≥60 y and TE history, 23.7% vs 19.5%).

Pt characteristics are listed in Table 1A. Compared with low risk pts, significantly more high risk pts were JAK2 V617F positive (P = 0.0143); fewer were CALR positive, and more were MPL positive. Pts with high-risk disease who were untreated had the highest proportion of palpable splenomegaly; mean palpable spleen length below the costal margin was greater in treated pts (low- and high-risk) than in untreated pts. Blood counts were similar across cohorts, except platelets were elevated for untreated high-risk pts. The proportion of pts with comorbidities was similar across cohorts; cardiovascular comorbidities were not as common among low- vs high-risk pts. Mean TSS was highest for low-risk pts, and was similar in both treated and untreated high-risk pts. Fatigue was the most severe symptom in all cohorts. Mean MPN-SAF TSS was significantly higher for low- vs high risk pts (P = 0.0007), as were several individual symptom scores (abdominal discomfort, P = 0.0081; concentration, P = 0.0014; numbness/tingling, P = 0.0361; night sweats, P < 0.0001; itching, P = 0.0131; bone pain, P = 0.0206; weight loss, P = 0.0469). Physician-reported signs and symptoms were generally more common in low- vs high-risk pts, with differences between risk groups reaching significance for headache (P = 0.0009) and abdominal pain (P = 0.0455).

Among currently untreated high-risk pts, 40.9% had not received any previous ET-directed therapy. Hydroxyurea (HU) was the most common ET-directed monotherapy at enrollment in both low- and high-risk treated pts (Table 1B). A small proportion of pts in both low- and high-risk treated groups was receiving >1 ET-directed therapy.

Conclusion: These real-world data from the MOST study indicate that despite treatment, low-risk pts had greater patient-reported symptom burden and physician-reported signs/symptoms than high-risk (treated or untreated) pts. This finding suggests that current management (most commonly with HU in this analysis) may not address symptoms in low-risk pts. Notably, nearly 60% of currently untreated high-risk pts had been previously treated, highlighting an unmet need for effective and tolerable second-line treatments in pts with high-risk ET. Further analyses from MOST will help define changes in the clinical and treatment characteristics of pts with ET over time.