Passamonti F, Parikh RC, Korgaonkar S, Chevli M, Yucel A, Rombi J, Zissler D, Davis KL, Slaff S. Patient characteristics, treatment patterns, and health outcomes in a real-world population of patients with myelofibrosis treated with fedratinib. Poster presented at the European Hematology Association (EHA) 2024 Hybrid Congress; June 13, 2024. Madrid, Spain.

BACKGROUND: Myelofibrosis (MF) is characterized by bone marrow fibrosis, splenomegaly, and constitutional symptoms. Fedratinib (FEDR), a selective Janus kinase-2 inhibitor (JAK2i), has shown improved clinical outcomes in clinical trials in patients (pts) with MF previously treated with ruxolitinib (RUX). Real-world (RW) evidence on FEDR treatment patterns and outcomes after RUX treatment is limited.

AIMS: To describe pt characteristics, FEDR treatment patterns, and evaluate clinical outcomes among pts with MF who received FEDR after discontinuing RUX treatment in RW settings in Canada (CAN), Germany (GER), and the United Kingdom (UK).

METHODS: We present an updated analysis of data collected through medical record review (Mar to Aug 2023) for pts with MF treated with FEDR in clinical practice. Eligible pts had intermediate (int)-2 or high-risk MF at FEDR initiation; had discontinued RUX due to treatment refractoriness, relapse, or intolerance; and had initiated FEDR after date of first availability (ie, CAN: Sep 21, 2020, GER: Feb 9, 2021, UK: Nov 1, 2021) up to 6 mo prior to data abstraction. Spleen size via palpation was required at FEDR initiation (baseline) and at least once within the first 6 mo of FEDR treatment. Pts who received allogeneic hematopoietic cell transplantation after MF diagnosis or participated in a JAK2i trial before FEDR initiation were excluded. Pt characteristics, FEDR treatment patterns, MF-related symptoms, and spleen size evaluations were reported descriptively. Overall survival (OS) and time to spleen size reduction (ie, spleen response) were estimated using the Kaplan-Meier method.

RESULTS: The final sample included 196 pts with MF (CAN: 45 [22.9%], GER: 86 [43.9%], UK: 65 [33.2%]). Median age at MF diagnosis and FEDR initiation was 65.8 and 68.7 y, respectively. Most pts were male (62.8%), White (82.7%), diagnosed with primary MF (76.5%), had int-2 risk MF (56.1%), and JAK2 v617F mutation (56.1%). Mean (standard deviation [SD]) Charlson Comorbidity Index score was 2.1 (1.3). Median time from RUX discontinuation to FEDR initiation was 1.2 mo. Common reasons for FEDR initiation were RUX failure (59.2%), FEDR efficacy (57.1%), and splenomegaly (54.6%). Over a median follow-up of 13.8 mo, 108 (55.1%) pts had ongoing FEDR treatment at record abstraction. Median treatment duration among pts with ongoing and discontinued FEDR treatment was 14.3 and 6.3 mo, respectively. Mean (SD) number of MF-related symptoms decreased from 3.5 (2.1) at baseline to 1.3 (1.6) at 6 mo post-FEDR initiation. Baseline MF-related symptoms completely resolved in 42.0% (66/157) of pts 6 mo after FEDR initiation. The proportion of pts with no MF-related symptoms increased from 4.6% at baseline to 37.3% at 6 mo after FEDR initiation (Figure). In the first 6 mo of FEDR treatment, moderate splenomegaly (palpable spleen: 11–20 cm) decreased from 56.1% to 17.8%, and severe splenomegaly (palpable spleen: > 20 cm) decreased from 24.5% to 5.9% (Figure). Overall, 66.8% of pts had a reduction in spleen size; median time to spleen response was 4.0 mo (95% confidence interval [CI], 4.0–5.0). Median OS from FEDR initiation was 29.8 mo (95% CI, 23.9–not estimable) with 1-y and 2-y OS rates of 85.9% (standard error [SE], 2.6) and 62.3% (SE, 7.3), respectively.

SUMMARY/CONCLUSION: In this study, 42.0% of pts with MF experienced complete resolution of MF-related symptoms and 66.8% had a spleen size reduction during the first 6 mo of FEDR treatment after RUX discontinuation. Study findings illustrate the RW clinical benefit of FEDR treatment and support results from FEDR clinical trials.

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