Primary myelofibrosis: Prognostic impact of non-driver mutations

Patients diagnosed with primary myelofibrosis (PMF) often present with non-driver mutations which are related to other myeloproliferative neoplasms. The presence of these non-driver mutations can influence the clinical phenotype and treatment response.

Recently, Hernández-Sánchez et al.¹ published results from a study in American Journal of Hematology investigating the impact of non-myeloproliferative neoplasm driver mutations in patients diagnosed with PMF. We summarize the key points below

Study design¹

• This study was performed across 60 Spanish sites (N = 312)
• Median age was 68 years
• A total of 20 genes out of 56 evaluated were consistently analyzed across all next-generation sequencing panels.
• Only pathogenic or likely-pathogenic variants with a variant allele frequency (VAF) of >1% were considered a mutation.

Key findings¹

• Non-driver mutations were identified in 72% of patients and 47% of patients had ≥2 non-driver mutations
• The most frequently identified non-driver mutation was ASXL1, followed by TET2 and SRSF2 (Figure 1)

Figure 1. Most frequently identified non-driver mutations in patients with PMF* 

*Adapted from Hernández-Sánchez, et al.¹

• The presence of any non-driver mutation resulted in a worse median overall survival (OS) vs patients with no non-driver mutations (p < 0.001)
  • 0 mutation: 12.4 years
  • 1 mutation: 8.7 years
  • ≥2 mutations: 4.4 years
• A VAF of >20% was shown to be an adverse prognostic factor

• Univariate analysis identified the following mutations to be associated with shorter OS: SRSF2 (p < 0.001), CBL (p < 0.001), SETBP1 (p = 0.012), TP53 (p = 0.016), U2AF1 Q157 (p = 0.021), NRAS (p = 0.032), and EZH2 (p = 0.034).
• Mutations identified as independent prognostic factors were: SRSF2 (p < 0.001), CBL (p = 0.003), EZH2 (p = 0.013), SETBP1 (p = 0.024), and ASXL1 with a VAF of >20% (p = 0.042).