In a German single-center study reported in The New England Journal of Medicine, Gagelmann et al determined that clearance of driver mutations after allogeneic hematopoietic stem-cell transplantation was associated with better outcomes in patients with myelofibrosis.
Study Details
The study involved data from 324 patients with primary myelofibrosis or secondary myelofibrosis (evolving from polycythemia vera or essential thrombocythemia) who underwent first transplantation after reduced-intensity conditioning between 2000 and 2023 at the Department of Stem Cell Transplantation at the University Medical Center Hamburg-Eppendorf in Hamburg, Germany.
Among the patients, 73% had JAK2 mutations, 23% CALR mutations, and 4% MPL mutations. Mutations were identified prior to transplantation and at 30 and 100 days after transplantation to determine clearance and effect on clinical outcomes.
Key Findings
At day 30 after transplantation, mutation clearance was found in 42% of patients with JAK2 mutations, 73% of those with CALR mutations, and 54% of those with MPL mutations; at day 100, the percentages of patients with clearance were 63%, 82%, and 100%, respectively.
The cumulative incidence of relapse at 1 year was 6% (95% confidence interval [CI] = 2%–10%) among patients with mutation clearance at day 30 and 21% (95% CI = 15%–27%) among those without clearance at day 30.
Disease-free survival and overall survival at 6 years were 61% and 74%, respectively, among patients with mutation clearance at day 30, and 41% and 60%, respectively, among those without clearance at day 30.
As noted by the investigators, mutation clearance at day 30 appeared to outperform traditional donor chimerism as a measure of response. Clearance at day 30 was independently associated with reduced risk of relapse or progression (hazard ratio [HR] = 0.36, 95% CI = 0.21–0.61), with this effect being greater than the effect of type of driver mutation.
The investigators concluded: “In patients with myelofibrosis, clearance of driver mutations at day 30 after transplantation appeared to influence relapse and survival, irrespective of the underlying driver mutation.”
Nicolaus Kröger, MD, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, is the corresponding author for The New England Journal of Medicine article.
Disclosures: For full disclosures of all study authors, visit NEJM.org.
