Real-World Clinical Outcomes of Patients with Myelofibrosis Treated with Ruxolitinib: Evidence from a Multinational Medical Record Review

Introduction: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by cytopenia, splenomegaly, and debilitating constitutional symptoms, such as fatigue, night sweats, weight loss, bone pain, and pruritus. Prior to the approval of the selective Janus kinase-2 (JAK2) inhibitor fedratinib for adults with Intermediate (Int)-2 or High-risk MF in 2019, ruxolitinib (RUX) was the only FDA-approved JAK inhibitor and considered standard of care; treatment (tx) options after RUX were limited. Furthermore, although about 60% of pts carry JAK2 mutations, not all patients respond to RUX. The aim of this study was to describe real-world tx patterns and determine unmet need in pts with MF treated with RUX.

Methods: We report interim data collected from the UK and USA as part of a global retrospective medical chart review of adult pts with Int-1, Int-2, or High-risk MF who started RUX tx between Jan 2012 and Dec 2016 in the USA, UK, Germany, Spain, Canada, and France, Pts were required to have discontinued RUX prior to data abstraction (Apr–May 2020). Prior tx was allowed, except for allogeneic hematopoietic cell transplantation or JAK2 inhibitor trial participation. Study measures included pt and tx characteristics at RUX initiation, tx patterns, dose modifications (DMs), and clinical outcomes. The rate of DMs (decrease or increase) during the first 6 months of tx was assessed. Recommended dose (REC) as per US FDA label of RUX was determined via baseline platelet count; atypical dose (ATY) was defined as non-REC RUX. The Kaplan–Meier method was used to estimate median overall survival (OS) from start of RUX tx. Descriptive statistics are used in this report.

Results: A total of 183 pts (USA: 105, UK: 78) were included in the analysis. Mean age at diagnosis was 63 years, 69% were male, and 82% were White. Most pts had primary MF (84%), Int-2-risk disease (51%), and JAK2 V617F driver mutation (67%).

RUX was first-line MF tx in 100 pts (55%). Of 140 pts with baseline platelet counts, 46% started on REC RUX, and 54% started ATY RUX. Of pts who initiated ATY RUX, those with platelet count below 200 ×10⁹/L were more likely to receive a higher dose; those with a platelet count above 200 ×10⁹/L, were more likely to receive a lower dose. The median time from diagnosis to RUX initiation overall was 1.3 months (mos); this was shorter in pts initiated on REC RUX and longer in pts initiated on ATY RUX (Table). The median duration of tx (DoT) was higher for pts who initiated ATY RUX vs REC RUX (Table).

Among pts who had a dose change (n = 61), change in platelet/neutrophil count (43%), and inadequate response (33%) were the main reasons for the first dose change; dose changes due to toxicity were more common with ATY RUX (33%) vs REC RUX (5%).

Eighty-six pts (47%) had clinician-defined inadequate response or progressed on RUX. Pts starting ATY RUX (63% vs 39% for REC RUX) or having a DM within 6 mos of initiation (59% vs 49% for no DM) had a higher proportion of progressive disease (PD). Of those with inadequate response/PD, 69% discontinued RUX and 22% continued RUX due to lack of other effective tx.

Twenty-eight percent of pts that started REC RUX discontinued RUX due to experiencing no additional clinical benefit after initial improvement; for pts who started ATY RUX, progression due to anemia (33%) was the main reason for discontinuation.

In pts who did not discontinue RUX immediately after inadequate response/PD, median time to RUX discontinuation from inadequate response/PD was higher in pts who received ATY RUX vs REC RUX (6.1 vs 1.9 mos).

Of 164 evaluable pts, 32 (20%) received post-RUX tx, most commonly hydroxyurea (28%) or lenalidomide (27%, USA only).

Median OS since RUX initiation was 44.2 mos. OS was shorter in pts who started ATY vs REC RUX (40.9 vs 43.1 mos) and those who had a DM vs no DM within 6 mos (38.6 vs 43.0). The most common causes of death were PD (34%) and progression to AML (19%) – pts who received DMs within the first 6 mos were more likely to die from progression to AML (27%) vs those with no DMs (19%).

Conclusions: In this population of adults with MF, we provide observational data that indicates DMs, including starting ATY RUX at higher or lower than REC doses, may be associated with poorer survival outcomes and higher rates of discontinuation due to PD. Relatively few pts received subsequent tx after discontinuing RUX, underscoring a significant unmet need for newer and more effective tx for MF.