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

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: 68Á7 AE 12 years; median followup: 3Á4 years (IQR 0Á4-8Á6)] from 2004 till 2018, we used a 35-variable frailty index (FI) to categorise patient's frailty status as fit (FI < 0Á2, reference), prefrail (FI 0Á2-0Á29) or frail (FI ≥ 0Á3). 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 1Á7, 1Á1-2Á5) and frail patients (HR 2Á9, 1Á6-5Á5), those with higher DIPSS score (HR 2Á5, 1Á6-3Á9) and transfusion dependency (HR 1Á9, 1Á3-2Á9) had shorter OS. In a subset analysis of patients on JAKi treatment (n = 222), frail patients (HR 2Á5, 1Á1-5Á7), patients with higher DIPSS score (HR 1Á7, 1Á0-3Á1) and transfusion dependence (HR 1Á7, 1Á1-2Á7) 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.

Quality of life independently predicts overall survival in myelofibrosis: Key insights from the COntrolled MyeloFibrosis Study with ORal Janus kinase inhibitor Treatment (COMFORT)‐I study

“…This is the first study that has identified this association among individuals with MF. Bankar et al 9 found that higher frailty scores were associated with worse survival and increased JAK inhibitor therapy failure in 439 chronic phase MF patients. Other contemporary investigations have examined multiparameter flow cytometry as a substitute for blast count and response to ruxolitinib treatment after 6 months as potential predictors of survival.…”

Towards a Personalized Definition of Prognosis in Philadelphia-Negative Myeloproliferative Neoplasms

“…Caramazza et al identified the latter in complex karyotype (CK) or sole or double abnormalities such as + 8, − 7/7q-, i(17q), inv(3), − 5/5q-, 12p-, or 11q23 rearrangements [58]. IPSS and DIPSS(-plus) are to date the prognostic scores recommended for PMF stratification by the most recent European treatment guidelines [26 Since MF is a disease of the elderly, some groups have tried to include also relevant comorbidities in conventional models, but with non-conclusive results [60,61].…”