Incidence, prevalence, and clinical outcomes of myelofibrosis with and without cytopenia in the United States

Abstract Introduction: Cytopenia in patients with myelofibrosis (MF) is characterized by presence of anemia and/or thrombocytopenia, and is a marker of advanced disease with higher symptom burden and risk of progression to leukemia and death. Limited information is available on the current incidence and prevalence of MF with and without cytopenia in the United States (US), as well as how MF-related clinical outcomes may differ by cytopenic status at diagnosis. Methods: Incidence and prevalence of MF in the US were extrapolated based on 2022 estimates from the Optum Research Database (ORD) and standardized to the US population by age, sex, and region using 2023 US census data. To examine MF-related clinical outcomes by baseline cytopenic status, adult patients with newly diagnosed MF (≥2 non-diagnostic claims with ICD-10 codes D75.81 or D47.4)from July 2016 to April 2023 were identified from ORD. Cytopenic status was defined as presence of anemia or thrombocytopenia based on diagnosis codes in medical claims at the time of MF diagnosis. The index date was the earliest date of MF diagnosis. Patients were required to have continuous health plan enrollment for 6 months before the index date (baseline) and ≥12 months after the index date unless deceased within 12 months (follow-up). The study excluded patients with: diagnosis of other primary cancer in baseline, missing demographic information, pregnancy or participated in clinical trials (baseline or follow-up). Overall survival (OS), progression to acute myeloid leukemia (AML), and receipt of hematopoietic stem cell transplantation (HSCT) in the follow-up period by baseline cytopenic status were assessed using Kaplan-Meier analyses to account for censoring. Results: The estimated US incidence of MF in 2023 was 1.56 (95% confidence interval (CI): 1.38-1.77) per 100,000 person-years. The incidence of cytopenic MF was 1.14 (95% CI: 1.01-1.28) per 100,000 person-years, while that of non-cytopenic MF was 0.42 (95% CI: 0.36-0.50) per 100,000 person-years. The prevalence of MF was 6.3 (95% CI: 6.0-6.7) per 100,000. The prevalence of cytopenic and non-cytopenic MF was 4.5 (95% CI: 4.2-4.8) and 1.8 (95% CI: 1.6-2.1) per 100,000, respectively. Of 1,532 patients who met the study criteria for comparing MF-related clinical outcomes by baseline cytopenic status, 1,074 (70%) were cytopenic at MF diagnosis, which is consistent with the overall standardized US incidence. Among those with cytopenic MF, 310 (29%) patients had bi-cytopenia, 695 (65%) had anemia only, and 69 (6%) patients had thrombocytopenia only. Patients with cytopenic MF were older than those with non-cytopenic MF (mean±SD: 73.9±10.7 vs 68.9±12.0 years, p<0.001); they also had a baseline Quan-Charlson comorbidity score that was nearly double that of patients with non-cytopenic MF (mean±SD: 2.2±2.2 vs 1.2±1.6, p<0.001). The median follow-up time from MF diagnosis was 21.5 months for patients with cytopenia and 32.5 months for those without cytopenia at baseline. The 5-year OS was halved in patients with cytopenia (32.8%, 95% CI: 28.8-36.8%) compared to those without cytopenia (64.6%, 95% CI: 58.3-70.2%). In patients with cytopenia, the median OS was 38 months (95% CI: 32-43), with median OS not reached for those without cytopenia (p<0.001). The 5-year probability of progression to AML was three times higher in patients with cytopenia (22.0%, 95% CI: 17.7-27.2%) compared to those without cytopenia (6.9%, 95% CI: 4.3-10.9%; p<0.001). Overall, 69 patients (4.5%) received HSCT, with similar rates observed among patients with and without cytopenia (4.8% vs 3.9%, p=0.477). Among patients who received HSCT, the median time to HSCT from MF diagnosis was 8 and 11 months in cytopenic and non-cytopenic patients, respectively.Conclusions: The 2023 estimated incidence of MF in the US was 1.56 per 100,000, with a prevalence of 6.3 per 100,000. Most patients with MF were cytopenic with anemia or thrombocytopenia at the time of diagnosis, which was associated with significantly worse outcomes, including higher rates of progression to AML and lower OS. Effective management of cytopenia is therefore critical when evaluating treatment options for MF.