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Association of frailty with clinical outcomes in myelofibrosis: a retrospective cohort study
Aniket Bankar1, Shabbir Alibhai2, Elliot Smith1
1Princess Margaret Cancer Centre, Toronto, ON, Canada.
Abstract:
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: 68·7 ± 12 years; median follow-up: 3·4 years (IQR 0·4-8·6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0·2, reference), prefrail (FI 0·2-0·29) or frail (FI ≥ 0·3). 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 1·7, 1·1-2·5) and frail patients (HR 2·9, 1·6-5·5), those with higher DIPSS score (HR 2·5, 1·6-3·9) and transfusion dependency (HR 1·9, 1·3-2·9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2·5, 1·1-5·7), patients with higher DIPSS score (HR 1·7, 1·0-3·1) and transfusion dependence (HR 1·7, 1·1-2·7) 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.
Insights
Frailty significantly impacts outcomes in myelofibrosis (MF). Frail patients face shorter survival and increased JAK inhibitor therapy failure, highlighting frailty as a key prognostic factor beyond traditional measures.
Area of Science:
- Hematology
- Oncology
- Geriatrics
Background:
- Limited understanding of frailty's impact on clinical outcomes in myelofibrosis (MF).
- Frailty assessment is crucial for predicting prognosis in chronic diseases.
Purpose of the Study:
- To investigate the association between frailty and overall survival (OS) in MF patients.
- To assess the impact of frailty on cumulative Janus Kinase inhibitor (JAKi) therapy failure.
- To compare frailty as a prognostic indicator against age, comorbidities, and performance status.
Main Methods:
- Retrospective cohort study of 439 chronic phase MF patients (2004-2018).
- Utilized a 35-variable frailty index (FI) to categorize patients as fit, prefrail, or frail.
- Multivariable analysis assessed associations with OS and JAKi failure using hazard ratios (HR).
Main Results:
- Higher frailty scores (prefrail and frail) were associated with significantly shorter OS.
- Frail patients on JAK inhibitors experienced a higher cumulative incidence of therapy failure.
- Higher DIPSS scores and transfusion dependency also predicted worse OS and JAKi failure.
Conclusions:
- Increased frailty is a significant predictor of worse overall survival in myelofibrosis.
- Frailty is associated with a higher risk of JAK inhibitor therapy failure in MF.
- Frailty index is a superior indicator of fitness and prognosis compared to age, comorbidities, and performance status.
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