Prevalence and Impact of Frailty on Outcomes in Myelofibrosis

Myelofibrosis (MF) patients have a high susceptibility to frailty that predicts poor overall survival rates, according to a study presented at the 12^th International Congress on Myeloproliferative Neoplasms.

 In a single-center, retrospective cohort study, researchers assessed 439 MF patients, of which 52% had Primary MF, 35%  had Post-Polycythemia Vera or Post-Essential thrombocythemia MF, and 13% had prefibrotic MF (average age, 71, 59% male) who were seen at Princess Margaret Cancer Center (PMCC) between January 2004 and December 2018. The researchers constructed a 35-variable Frailty Index (FI) model to categorize each patient as Fit (FI 0-0.19), Pre-frail (FI 0.2-0.29) or Frail (>0.3) at the time of their initial visit to PMCC.

The study’s key endpoint events were specified as all-cause mortality or transformation to acute myeloid leukemia (AML). The researchers evaluated the effect of each patient category using a Cox proportional hazards model that measured age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, Hematopoietic Cell Transplant-Co-morbidity Index (HCT-CI), Dynamic International Prognostic Scoring System (DIPSS) score, transfusion requiring anemia, and type of driver mutations. Data on driver mutations were available in 401 patients, of which 73% had JAK2 mutation, 18% had CALR mutation, 5% had an MPL mutation, and 3.4% were triple negative. The average follow-up in this study was 2.1 years.

The results of the study showed that the presence of a JAK2 driver mutation was notably linked with a higher Frailty Index (FI) compared to other driver mutations. A subset analysis of patients with complete molecular profiling revealed that patients with high risk mutations had significantly higher FI scores on average compared to patients without HMR. The researchers observed that independent factors that predicted poor survival included pre (HR=1.71; 95% CI 1.17 to 2.52), frail status (HR=3.38; 95% CI, 1.86 to 6.14), higher DIPSS risk stratification (HR=2.46; 95% CI, 1.59 to 3.01), and transfusion-requiring anemia (HR=2.04; 95% CI, 1.38 to 3.0).

The researchers wrote in their conclusion that: “Further research is needed to understand how to modify frailty.”

Bankar A, et al. Prevalence and Impact of Frailty on Outcomes in Myelofibrosis. Presented at the 12^th International Congress on Myeloproliferative Neoplasms; October 24-25, 2019; New York, NY.