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Impact of mutated JAK2 allele burden on the outcomes in PV and ET
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A prospective study which measured changes in JAK2 and CALR variant allele frequency (VAF) in patients with polycythemia vera (PV) and essential thrombocythemia (ET) treated with ruxolitinib has been published in the American Journal of Hematology by Guglielmelli et al.1 Changes in mutant VAF were measured alongside complete clinical and hematological response (CCHR) and other clinical outcomes to establish whether a correlation exists between mutated JAK2 allele burden and clinical outcomes. |
| Key learnings |
| Overall, the median JAK2 VAF reduced from 68% to 3.5% over the study period. |
| A durable molecular response (DMR) defined as a stable VAF ≤2% for ≥1 year was observed in 20% of patients, a partial MR (PMR) in 25%, and a lack of MR in 56% of patients. |
| CCHR was reported in 69% of patients and was independent of the degree of molecular response. |
| Increased DMR was correlated with longer duration of CCHR, reduced progression to myelofibrosis, and increased rates of myelofibrosis-free, event-free, and progression-free survival. |
| Factors predicting DMR and reduced progression to myelofibrosis included a baseline JAK2 VAF <50% and a VAF reduction ≥35% after 2 years of treatment. |
| The findings underscore the significance of targeted molecular response in managing myeloproliferative neoplasms, advocating for personalized treatment strategies based on JAK2 VAF dynamics. |
- Guglielmelli P, Mora B, Gesullo F, et al. Clinical impact of mutated JAK2 allele burden reduction in polycythemia vera and essential thrombocythemia. Am J Hematol. 2024;99(8):1550-1559. DOI: 1002/ajh.27400
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