Study Validates Prognostic Models, Genetic Markers in Patients With Myelofibrosis

A retrospective cohort study presented at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas, assessed real-world outcomes for patients with myelofibrosis (MF) by validating various prognostic models and identifying key genetic factors.

The study included 284 Taiwanese patients with different stages of MF, such as prefibrotic MF, primary MF, and post-polycythemia vera (post-PV) or post-essential thrombocythemia (post-ET) MF. Of those, 185 had cryopreserved bone marrow samples available for gene sequencing.

After a median follow-up of 4.6 years, the median overall survival (mOS) was 11.7 years, and the five-year leukemic transformation rate was 9.7%. Several prognostic models, including the International Prognostic Scoring System, the Dynamic International Prognostic Scoring System (DIPSS), DIPSS Plus, a genetically inspired prognostic scoring system, and the Myelofibrosis Secondary to PV and ET Prognostic Model, were able to effectively stratify survival, though the Mutation-Enhanced International Prognostic Score System (MIPSS70+ Version 2.0 model) performed slightly less effectively (P=0.002).

High-molecular-risk (HMR) mutations, such as ASXL1, SRSF2, and EZH2, were linked to worse overall survival (P<0.001), especially in patients with a low JAK2V617F variant allele burden (VAF <0.75). For those patients, the median survival dropped significantly (mOS 4.1 years versus 19 years in high VAF cases; P=0.006). TP53 mutations also predicted poor prognosis (mOS 7.4 versus 19 years; P=0.03), though no survival difference was found between single-hit and multi-hit mutations.

Patients with a cytopenic phenotype, characterized by older age, higher circulating blasts, and fewer JAK2 mutations, had shorter survival (mOS 9.4 versus 14.8 years; P<0.001) compared with those with a proliferative phenotype. A multivariable Cox regression analysis, including factors such as age and high-risk cytogenetics, confirmed that the cytopenic phenotype was independently associated with inferior survival (HR 1.91; P=0.047).

According to the investigators, “This study delineates the characteristics of patients with MF in Taiwan and validates the prognostic significance of multiple scoring systems, thereby complementing the limited data available on the Asian population.”

Reference

Chang YS, Wang YH, Wei CH, et al. Clinico-molecular risk stratification in 284 patients with pre-fibrotic and overt myelofibrosis. Abstract #MPN-239. Presented at the Society of Hematologic Oncology Annual Meeting; September 4-7, 2024; Houston, Texas.