Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study

There is limited understanding of the impact of frailty on clinical outcomes in patients with myelofibrosis (MF). In this retrospective cohort study on 439 chronic phase MF patients [mean age: 68 center dot 7 +/- 12 years; median follow-up: 3 center dot 4 years (IQR 0 center dot 4-8 center dot 6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0 center dot 2, reference), prefrail (FI 0 center dot 2-0 center dot 29) or frail (FI >= 0 center dot 3). The association of frailty with overall survival (OS) and cumulative JAK inhibitor (JAKi) therapy failure was measured using hazard ratio (HR, 95% CI). In multivariable analysis, prefrail (HR 1 center dot 7, 1 center dot 1-2 center dot 5) and frail patients (HR 2 center dot 9, 1 center dot 6-5 center dot 5), those with higher DIPSS score (HR 2 center dot 5, 1 center dot 6-3 center dot 9) and transfusion dependency (HR 1 center dot 9, 1 center dot 3-2 center dot 9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2 center dot 5, 1 center dot 1-5 center dot 7), patients with higher DIPSS score (HR 1 center dot 7, 1 center dot 0-3 center dot 1) and transfusion dependence (HR 1 center dot 7, 1 center dot 1-2 center dot 7) had higher cumulative incidence of JAKi failure. Age, comorbidities, ECOG performance status, and MPN driver mutations did not impact outcomes. Thus, higher frailty scores are associated with worse OS and increased JAKi failure in MF, and is a superior indicator of fitness in comparison to age, comorbidities, and performance status.