Whole Blood Mutation Allele Frequency Is a Weak Biomarker in Polycythemia Vera

The monitoring of whole blood mutation allele frequency (MAF) had only weak prognostic value in certain patients with polycythemia vera (PV), and had no prognostic value for predicting survival, according to data presented at the 2022 American Society of Hematology Annual Meeting.

Patients with PV undergo regular monitoring of whole blood JAK2V617F MAF in both clinical trials and clinical practice, but whole blood MAF does not capture core myeloproliferative neoplasm (MPN) cell biology, explained Ghaith Abu-Zeinah, MD, of Richard T. Silver, M.D. Myeloproliferative Neoplasms (MPN) Center at Weill Cornell Medicine in New York, and colleagues.

Therefore, they conducted this study to determine the value of whole blood MAF as a biomarker and to see whether a reduction in whole blood MAF was associated with improved survival.

Whole blood MAF data was available for 260 patients between 2003 and 2021. Serial MAF within five years from baseline, before progression, was available for 165 patients. The researchers categorized the change in MAF from baseline to the lowest MAF within five years as molecular response (MR) 10 (for a 10% or greater relative reduction), MR20 (≥20% reduction), MR30 (≥30% reduction), or MR50 (≥50% reduction).

MR10 was achieved in 45% of patients, MR20 in 38%, MR30 in 35%, and MR50 in 25%. Patients who achieved MR at any level were more likely to be receiving interferon (P<.05).

Change in MAF was not prognostic for event-free or overall survival. However, MR20 to MR50 was linked with improved myelofibrosis (MF)-free survival (P=.03). According to the researchers, the optimal area under the curve across MR levels and time was modest, indicating that MR had only a fair performance as a biomarker for MF.

“Larger, long-term, prospective studies are necessary and could establish optimal definition of MR as a monitoring biomarker,” the researchers wrote in the abstract. “But the preliminary signal is modest and we believe this effort would be better spent developing new biomarkers, such as MPN fitness, that capture disease biology.”

Reference

Abu-Zeinah G, Tokumori FC, Erdos K, et al. 3034 Polycythemia vera patients with >20% reduction in whole blood JAK2V617F allele frequency have improved myelofibrosis-free survival but not overall survival. Abstract #3034. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.