Real-world characteristics and treatment patterns in patients with essential thrombocythemia by thrombosis risk levels Free

Essential thrombocythemia (ET) is a rare myeloproliferative neoplasm characterized by elevated platelet counts from abnormal bone marrow production. The International Prognostic Score of Thrombosis for Essential Thrombocythemia (IPSET-thrombosis) has been used to classify patients into different risks levels and tailor treatment based on age, history of thrombosis, and Janus kinase 2 (JAK2) mutation status. There is very limited literature regarding contemporary characteristics and treatment patterns of patients with ET by risk levels in real world populations.

Patients with newly diagnosed ET (ICD-9 code 238.71 or ICD-10 code D47.3)from July 2012 to March 2024 were identified from Optum's Market Clarity research database of integrated claims and electronic health records. Index date was the earliest date of ET diagnosis. Patients were required to have continuous enrollment for 6 months before (baseline) and ≥12 months after index date unless deceased within 12 months (follow-up); they were also required to receive cytoreductive treatment after diagnosis. Patients were classified by IPSET-thrombosis risk levels as very low or low risk, intermediate risk, or high risk. Patients without sufficient information for risk classification were retained as an unclassified risk group. Demographic and clinical characteristics (including National Cancer Institute Charlson Comorbidity Index (NCCI)) and treatment patterns (lines of therapy (LOTs), time to cytoreductive treatment and time to next treatment (rwTTNT)) were stratified by risk levels.

Of 3,538 patients with ET included in the study, 111 (3.1%) had very low/low risk, 92 (2.6%) had intermediate risk, 903 (25.5%) had high risk, and 2432 (68.7%) had unclassified risk; their median age was 53, 72, 74, and 70 years, respectively. A higher proportion of patients was female, varying from 59-62% across all risk levels. Between 68-75% of patients were non-Hispanic white across risk levels, although non-Hispanic black comprised relatively higher proportions in the high (12.3%) and unclassified (13.0%) levels. Patients in the high risk group had the highest proportion of patients with an NCCI score of 3+ (29.8%, vs. 12.0% in intermediate, 10.1% in unclassified, and <4.5% in very low/low risk levels). The majority of patients in the very low/low risk level had an NCCI score of 0 (75.7%, vs. 43.5% in intermediate, 27.0% in high, and 56.4% in unclassified risk). A larger proportion of patients in the high risk group had hypertension (69.1%, vs. 60.9% in intermediate, 27.0% in very low/low, and 50.7% in unclassified risk levels) and diseases of the heart (60.2%, vs. 30.4% in intermediate, 18.0% in very low/low, and 33.7% in unclassified risk levels). The median time from ET diagnosis to cytoreductive treatment decreased by risk level, ranging from 190 days for very/low to 86 days for high risk. Furthermore, median rwTTNT decreased in subsequent LOTs, irrespective of risk levels. Overall, hydroxyurea (HU) monotherapy was the most common treatment across LOTs, ranging from 91% in 1L to 75% in 4L. In 1L, 73% of very low/low risk patients, 92% of intermediate risk patients, 87% of high risk patients, and 94% of unclassified risk patients received HU monotherapy. Anagrelide and ruxolitinib were also among the top 3 regimens although they were very uncommon. Patients had a median 1L duration of 229, 365, 305, and 339 days across very low/low to unclassified risk levels, with duration shortening in later LOTs. Discontinuation was the most common reason for end of the 1L, which varied from 50% in very low/low risk patients to 61% in intermediate risk patients. In high risk patients ending 1L, in addition to the 56% discontinuing medication, 6% had disease progression, and 7% ended the line due to death. The proportion of patients with 2L treatment ranged from 50-64% across risk levels, with a median 2L duration of 189-248 days. Approximately 49-70% of patients with the 2L subsequently initiated 3L treatment.

In this contemporary real-world study, the vast majority of ET patients who received cytoreductive treatment were in the intermediate and high risk level. Comorbidities and treatment pattern related outcomes were worse among patients in the intermediate and high risk groups. HU remained the most commonly used treatment option by a large margin across IPSET-thrombosis risk levels, highlighting the high unmet need for new and effective drugs.