Clearance of driver mutations after HSCT predicts myelofibrosis relapse, survival
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Key takeaways:
- Patients with myelofibrosis who cleared their mutations 30 days following stem cell transplantation experienced fewer relapses.
- They also achieved longer DFS and OS.
Patients with myelofibrosis who cleared driver mutations within 30 days after hematopoietic stem cell transplantation survived longer and exhibited reduce risk for relapse, according to study results.
Evaluating mutation clearance with simple blood tests “will become clinical practice” for predicting outcomes, Nicolaus Kröger, MD, medical director of the department of stem cell transplantation at University Hospital Hamburg-Eppendorf in Germany, told Healio.
“It was very surprising and completely unexpected that clearance of the mutation can be achieved in patients with myelofibrosis so early after the transplant procedure and showed such high impact on later relapse,” he said.
Background and methods
Approximately 90% of patients diagnosed with myelofibrosis have JAK2, CALR or MPL driver mutations, according to study background. In addition, 10% to 30% of individuals relapse following HSCT.
Prior research showed patients with acute myeloid leukemia or myelodysplastic neoplasms have a higher risk for relapse if they have residual disease.
Kröger and colleagues investigated the association between clearance of driver mutations and outcomes among 324 patients (median age, 60 years; 58% men) diagnosed with primary or secondary myelofibrosis who underwent stem cell transplantation at University Hospital Hamburg-Eppendorf between 2000 and 2023.
Most patients had a JAK2 mutation (73%), whereas a smaller percentage had CALR (23%) or MPL (4%) mutations.
Researchers evaluated driver mutations before transplantation and 30, 100 and 180 days after.
The association of driver mutation clearance and relapse served as the primary outcome.
Results and next steps
At 30 days after transplant, mutation clearance occurred among 42% of patients who had JAK2 mutations, 73% who had CALR mutations and 54% who had MPL mutations.
Of 271 patients evaluable at 100 days after transplant, mutation clearance occurred among 63% of those who had JAK2 mutations, 82% who had CALR mutations and 100% who had MPL mutations.
Individuals who had mutation clearance at day 30 had a lower risk for relapse at 1 year (6% vs. 21%) and 6 years (15% vs. 32%) than those who did not. Researchers also reported higher rates of 6-year DFS (61% vs. 41%) and 6-year OS (74% vs. 60%) among those with mutation clearance.
Day 30 mutation clearance “appeared to outperform” donor chimerism measuring response at day 30, researchers wrote.
Patients with mutation clearance exhibited a lower risk for relapse or progression (HR = 0.36; 95% CI, 0.21-0.61), independent of age at transplantation, disease phase, type of myelofibrosis and mutation genotype.
Researchers acknowledged study limitations, including the cohort’s lack of diversity and a small number of patients in certain subgroups, including those with MPL or TP53 mutations.
“Since we know now how important clearance of the mutation by day 30 or day 100 after transplantation is, additional cell therapies [such as] donor T cells or others to achieve molecular negativity in those patients who are not negative will be investigated,” Kröger told Healio. “These data provide the scientific rationale for further intervention studies, which will increase the cure rate in these patients after allogeneic hematopoietic stem cell transplantation.”
For more information:
Nicolaus Kröger, MD, can be reached at n.kroeger@uke.de.
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