PS1463 SURVIVAL OUTCOMES IN MYELOFIBROSIS PATIENTS TREATED WITH RUXOLITINIB: A POPULATION‐BASED COHORT STUDY IN SWEDEN AND NORWAY
Authors: F. Schain, E. Vago, J. He, J. Liwing, C. Song, C. Löfgren, M. Björkholm
Journal: HemaSphere (2019)

Background: Allogeneic stem cell transplantation, the only curative option for myelofibrosis (MF), is rarely performed in Nordic countries due to high morbidity and mortality. Ruxolitinib (RUX) is effective in symptom management and has potential survival benefits in MF. However, discontinuation rates are high due to disease progression and/or side effects. Salvage therapies after RUX discontinuation are limited and the prognosis is poor. Aims: This retrospective study was conducted to assess survival outcomes in Swedish and Norwegian MF patients who received RUX (the full cohort), and in those who discontinued RUX (the sub‐cohort), using data from national registries. Methods: Patients ≥18 years of age with an MF diagnosis (mostly assumed to have intermediate‐ 2 and high‐risk MF) in the national cancer registry between 2000 and 2016 who had at least one record of RUX in the national prescription registry between 2013 and 2017 were included, and data from this cohort were linked to the cause of death registry. Patients were followed from RUX initiation (the full cohort) or RUX discontinuation (the sub‐cohort) until death or end of the study (September 30, 2017 [Norway]; November 3, 2017 [Sweden]). Overall survival (OS), relative survival (RS) and excess mortality rate ratio (EMRR) were estimated in both cohorts. The applied additive hazard model was adjusted for age, sex, calendar year, and country (RS). EMRRs were estimated to compare excess mortality between subgroups based on age, sex, and time from MF diagnosis to RUX initiation. Loss in life expectancy was calculated as difference between the life expectancy from RUX initiation for the full cohort (and RUX discontinuation for the sub‐cohort) and life expectancy in the general population using a flexible parametric model adjusted for age, sex, calendar year, and country. Results: Of 190 identified patients with MF who received RUX, 24 died during the observation period. In the full cohort (n = 190), median RUX treatment duration was 11.5 months, median age at MF diagnosis was 64 years, and 52.6% of the patients were male. For the full cohort, one‐year and 5‐year OS from RUX initiation were 0.80 (95% confidence interval [CI]: 0.88, 0.96) and 0.52 (95% CI: 0.42, 0.64), respectively. The corresponding numbers for RS were comparable to OS. Median age of the sub‐cohort at RUX discontinuation was 70 years and 56% of the patients were male. In the sub‐cohort (n = 71; Sweden: 37, Norway: 34), median OS and RS from RUX discontinuation were 16.0 months (95% CI: 6.3, Not Estimable) (Figure). The average loss in life expectancy from RUX initiation was 11 years per person in the full cohort, and 12 years per person from RUX discontinuation in the sub‐cohort. In the full cohort, excess mortality was more prominent in the patients &gt;70 years of age (EMRR: 3.16; 95% CI: 1.34, 7.40) compared with the patients &lt;60 years of age at the time of RUX initiation. Sex or time to RUX initiation after MF diagnosis were not significantly associated with excess mortality. In the sub‐cohort, none of the studied variables was significantly associated with excess mortality. After RUX discontinuation, the Swedish patients (n = 37) received the following drugs: glucocorticoids (n = 19), hydroxyurea (n = 5), busulfan (n = 3), danazol (n = 5), and lenalidomide (n = 1). No data on subsequent therapies were available for Norwegian patients. Summary/Conclusion: MF patients in Sweden and Norway who discontinued RUX had dismal survival outcomes and limited salvage treatment options, highlighting the need of improved therapeutic options. image