Burden and Clinical Outcomes in Patients (pts) with Myelofibrosis (MF) and Anemia Treated with Ruxolitinib (RUX): Data from the Veterans Affairs Corporate Data Warehouse (VACDW)
Authors: Mascarenhas John O. , Perkins Aaron R. , Shih Yu-Hsuan , Tang Derek , Vergara Sara , Alvarez Carlos A. 
Published: December 2024

Introduction: Patients with MF typically present splenomegaly, constitutional symptoms, thrombocytopenia, and anemia. RUX is a JAK 1/2 inhibitor indicated to treat intermediate and high-risk MF; however, RUX causes myelosuppression, increasing the risk of persistent and worsening anemia. Understanding real-world (RW) management of anemia and clinical outcomes for pts with MF receiving RUX is critical to informing clinical decisions.
Objective: To highlight the burden of anemia by describing RW pt characteristics, treatment (tx) patterns, and clinical outcomes in pts with MF receiving RUX.
Methods: This retrospective cohort study used electronic health records and claims data from the US VACDW with a study period from earliest data available through December 31, 2023. Eligible pts were ≥18 y old, had ≥1 inpatient or 2 outpatient claims on different dates for MF, ≥1 inpatient or 2 outpatient claims on different dates for anemia (3 mo prior to initial MF diagnosis through end of study period), received RUX after January 1, 2013, had 6 mo of pre-index data, and ≥6 mo of follow-up or until death. Index was defined as RUX start date. Pts with other primary cancers within 1 y before MF diagnosis or with prior/concurrent clinical trial participation were excluded. Pt characteristics, tx patterns including RUX and supportive care for anemia (danazol, erythropoiesis-stimulating agents [ESAs], immunomodulatory drug [IMiD®] agents, red blood cell transfusions [RBCT]) were reported descriptively. Transfusion dependence (TD) and non-TD (NTD) at RUX initiation were defined as having ≥1 or 0 unique dates with RBCT, respectively, in the 6 wk on or before the index date. The Kaplan-Meier method was used to analyze time to tx discontinuation (TTD) and overall survival (OS) from index date. Multivariable Cox proportional hazards models were used to evaluate the associations of TD status and hemoglobin (Hb) levels at RUX initiation with TTD and OS, adjusted for age, sex, race/ethnicity, index year, time from initial MF diagnosis to RUX initiation, Charlson Comorbidity Index (CCI), platelet counts at RUX initiation, and maximum RUX total daily dose achieved.
Results: A total of 629 pts were included. Mean age was 71.8 y, 96.3% of pts were male, 78.5% were White, 40.6% had a CCI ≥3, and 68.0% had anemia on or before index. At RUX initiation, 122 (19.4%) pts were TD and 507 (80.6%) were NTD; 50.9% of TD pts and 38.1% of NTD pts had CCI ≥3; mean Hb levels were 8.0 g/dL for TD pts (n=119; 96.6% &lt;10.5 g/dL) and 11.5 g/dL for NTD pts (n=399; 41.4% &lt;10.5 g/dL); 42.0% and 24.3% of TD (n=119) and NTD pts (n=387) had platelet counts &lt;150 109/L, respectively. Median follow-up was 15.7 mo (range, 0.4-130.0) for TD pts and 26.8 mo (range, 0.1-122.4) for NTD pts. Median RUX tx duration was 8.9 mo in TD pts and 17.2 mo in NTD pts. &lt;1% of pts started RUX at a dose of 25mg twice daily (bid). The most common RUX starting dose was 5mg bid for TD pts (24.6%) and 10mg bid for NTD pts (25.9%). Among pts who discontinued RUX (n=416 [66.1%]), the most common dose at RUX discontinuation was 10mg and 5mg bid for both TD (n=85 [69.7%]; 10mg: 22.4%, 5mg: 21.2%) and NTD pts (n=331 [65.3%]; 10mg: 19.9%, 5mg: 22.1%). For TD pts, 92.6% received anemia supportive care after RUX initiation. 38.5% received danazol, ESAs, or IMiD agents, 91.0% received RBCT. Median time from RUX initiation to first RBCT was 1.0 mo (range, 0.0-18.3). For NTD pts, 43.6% received anemia supportive care after RUX initiation. 18.5% received danazol, ESAs, or IMiD agents, 36.5% received RBCT. Median time from RUX initiation to first RBCT was 8.0 mo (range, 1.4-102.9).
Median TTD was 16.7 mo (95% confidence interval [CI], 9.2-19.2) for TD pts and 25.4 mo (95% CI, 22.7-30.2) for NTD pts. While median OS was not reached, 85% of NTD pts and 72% of TD pts survived 24 mo after initiating RUX. Adjusted models showed TD pts had a higher risk of RUX discontinuation (hazard ratio [HR], 1.58; 95% CI, 1.20-2.09) or death (HR, 2.03; 95% CI, 1.23-3.36), which was also observed for pts with Hb levels &lt;10.5 g/dL at RUX initiation.
Conclusions: This study showed a significant anemia and RBCT burden in pts with MF receiving RUX in RW clinical practice. At RUX initiation, TD pts had a lower starting RUX dose and discontinued RUX earlier than NTD pts. Shorter OS was also observed for pts who were TD or had Hb levels &lt;10.5 g/dL at RUX initiation. Treatment strategies that can manage anemia and RBCT burden remain an important need for pts with MF receiving RUX.