In patients with primary or secondary myelofibrosis, mutations in the calreticulin (CALR) and Janus kinase 2 (JAK2) genes may be associated with prognosis, according to results reported in the American Journal of Hematology.
Patients included in the study had been diagnosed with myelofibrosis and had previously undergone genetic testing for mutations in Janus kinase 2 (JAK2), thrombopoietin receptor (MPL), and calreticulin (CALR) genes. Next-generation sequencing of patient samples was also performed to identify any high-risk mutations in several other genes.
In this study, 291 patients had primary myelofibrosis and 145 had secondary myelofibrosis. Most patients with PMF showed mutations in JAK2 (71%), CALR (16%), or MPL (7%). Approximately 7% had triple-negative (TN) status for mutations in these genes.
Median overall survival (OS) with primary myelofibrosis was 60.5 months with mutated JAK2, 101.8 months with mutated MPL, not reached with mutated CALR, and 30.1 months for TN patients.
Nearly all patients with secondary myelofibrosis showed mutations in JAK2 (75%), CALR (19%), or MPL (5%), and only 1% had TN status. Median OS for patients with secondary myelofibrosis was 81.8 months with mutated JAK2, 20.4 months with mutated MPL, and 161 months with mutated CALR.
In both myelofibrosis cohorts, JAK2 mutations, compared with CALR mutations, were associated with age above 65 years and lower platelet counts (< 100,000/mL). In the primary myelofibrosis cohort, in comparison with CALR mutations, JAK2 mutations showed associations with additional factors, including constitutional symptoms, the presence of 2 or more high-risk mutations, and mutations in U2AF1 Q157 and SRSF2 genetic regions. U2AF1 Q157 and SRSF2 mutations showed low prevalence in JAK2-mutated patients with sMF.
A multivariate analysis showed an apparent benefit of CALR mutations in terms of improved prognosis (hazard ratio [HR], 0.15; P =.033). In this analysis, mutations in ASXL1 (HR, 7.0; P <.001) and U2AF1 Q157 (HR, 8.8; P =.003) genetic regions were linked to poorer prognosis.
The study authors stated in their report, “We validated the favorable prognostic impact of CALR mutations in both [primary and secondary myelofibrosis] in addition to the inferior prognosis of TN disease in primary myelofibrosis.”
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
- Kuykendall AT, Talati C, Padron E, et al. Driver mutation-specific clinical and genomic correlates differ between primary and secondary myelofibrosis [published online August 23, 2019]. Am J Hematol. doi:10.1002/ajh.25625