Mutation Clearance After Allogeneic Stem Cell Transplantation as Prognostic Indicator for Patients With Myelofibrosis
Mutation driver clearance 30 days after allogeneic hematopoietic stem cell transplantation (alloHSCT) was associated with decreased risk of relapse and improved survival, regardless of mutation type, according to study results published in The New England Journal of Medicine.
For the treatment of MF, alloHSCT remains the only curative therapy for patients with driver mutations as hallmark indicators of disease. However, the role of driver mutation clearance after alloHSCT and its prognostic significance have not been well established.
Researchers assessed the impact of driver mutation clearance on cancer outcomes at 30, 100, and 180 days post-alloHSCT. The primary end points were disease-free survival and relapse. Patients with MF undergoing HSCT following reduced intensity (N = 324), including JAK2-mutated (73%), CALR-mutated (23%), and MPL-mutated (4%) subtypes, were included.
At day 30 post-HSCT, mutation clearance was observed in 42% of patients with JAK2 mutations, 73% with CALR mutations, and 54% with MPL mutations. Mutation clearance increased by day 100 to 63%, 82%, and 100%, respectively. In terms of relapse, the cumulative incidence of relapse at 1 year was 6% (95% confidence interval [CI], 2 to 10) among patients with mutation clearance at day 30, compared to 21% (95% CI, 15 to 27) among patients without clearance at day 30.
At 6 years, among patients who achieved clearance at day 30, disease-free survival (61%) and overall survival (74%) were higher than patients who did not achieve clearance at day 30 (41% and 60%, respectively). The mutation clearance at day 30 was superior to traditional donor chimerism as a predictor of relapse risk (HR, 0.36; 95% CI, 0.21 to 0.61) and appeared to mitigate prognostic differences among driver mutation subtypes.
“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,” the researchers concluded.
Source:
Gagelmann N, Quarder M, Badbaran A, et al. Clearance of Driver Mutations after Transplantation for Myelofibrosis. New England Journal of Medicine. Published online January 8, 2025. doi: 10.1056/nejmoa2408941
