Prevalence and association of frailty with clinical outcomes in myeloproliferative neoplasms: a population-based study

Clinical implications of frailty in myeloproliferative neoplasms (MPN)- essential thrombocythemia (ET), polycythemia vera (PV), myelofibrosis (MF) is unknown. In this population-based study, all incident cases of MPN from Ontario cancer registry between 2004-2019 (N=10,336, ET=5,108; PV=3,843; MF=1,385) and their matched controls (for age, sex, residence, income) in 1:4 ratio were included. Baseline frailty measured using Johns Hopkins Adjusted Clinical Groups frailty indicator and McIsaac’s frailty index (mFI), categorized as fit, prefrail, or frail if mFI <0.10, 0.11-0.20, > 0.20) was significantly higher in ET, PV and MF compared to matched controls [standardized mean difference 0.27, 0.27 and 0.28]. Over 23%, 20% and 34% patients with ET, PV and MF were frail or prefrail despite younger age (<65 years) or minimal comorbidities. In Cox-proportional regression, frailty was independently associated with worse overall survival (OS) after adjusting for age, sex, comorbidities compared to mFI-fit patients: hazard ratio (95% CI) for OS for mFI-prefrail and mFI-frail patients were: 1.6 (1.3-1.9), and 3.6 (2.9-4.4) in ET; 1.3 (1.1-1.5) and 2.7 (2.1-3.4) in PV, and 1.2 (1.0-1.5) and 2.0 (1.5-2.7) in MF. MPN patients have substantially higher prevalence of frailty compared to matched controls which is associated with reduced OS, independent of age or comorbidities.