Ruxolitinib (RUX) retreatment in patients (Pts) with myelofibrosis (MF): Real-world evidence on pt characteristics and outcomes.

Abstract

e19535 Background: RUX is a JAK1/JAK2 inhibitor FDA-approved for treatment (tx) of int/high risk MF. In the COMFORT studies, RUX reduced spleen volume in pts with MF (primary endpoint), with a median time to response of 3 mo. Case reports and clinical studies have shown some pts’ symptoms and/or splenomegaly improve upon RUX reinitiation after interruption. In the era of novel JAK inhibitors (JAKi), dose optimization and identifying indicators for tx changes remain major challenges. This study describes tx patterns and clinical outcomes of pts with MF with RUX interruption and retreatment in community-based clinical practices. Methods: Two independent patient care data sources were queried (not directly compared): (1) Cardinal Health Oncology Provider Extended Network (OPEN), (2) HealthCore Integrated Research Environment (HIRE); retrospective review of medical charts was conducted. Rigorous entry criteria for this analysis included: age ≥18 y; primary MF (PMF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF diagnosis between 1/1/2012–12/31/2016 (OPEN) or 1/2013–11/2017 (HIRE); use of RUX for MF; and documented physician-directed RUX interruption. MF-related symptoms, splenomegaly, and tx dose and patterns were analyzed. Results: 26 pts met entry criteria (Table). Pre-interruption median (IQR) RUX tx duration was 123 (57–391, OPEN) and 110 (37–148, HIRE) days; 50% had tx interruption within 3 mo. Most interruptions were for adverse events (AEs; 50% and 71%, respectively), followed by (in OPEN) alternative tx (17%), disease progression (8%), no response (8%), or loss of response (8%). After restarting RUX, median (IQR) retreatment duration was 196 (54–553) and 166 (108–262) days, respectively. Symptoms improved in 45% and 43% of evaluable pts, respectively, and spleen size improved in 40% and 33%. Conclusions: Consistent with previous reports, MF symptoms and spleen size improved with RUX retreatment in some pts. While RUX was discontinued for various reasons, one reason for clinical improvements upon reinitiation may be that tx was discontinued before deriving full JAKi benefit. Future studies are warranted investigating JAKi tx sequencing and reinitiation. [Table: see text]