Molecular measurable residual disease in NPM1-mutated acute myeloid leukaemia (UK NCRI AML17)
Detecting leftover NPM1-mutated leukaemia in the blood after the second course of chemotherapy identified patients very likely to relapse, and proved a better guide than genetics at diagnosis to who needs a transplant.
Overview
Prospective study within the AML17 trial of 346 patients with NPM1-mutated AML monitored by quantitative PCR for NPM1 transcripts in blood and marrow after each course.
Persistence of NPM1 transcripts in peripheral blood after the second chemotherapy course was found in 15 percent and predicted a three-year relapse rate of 82 percent against 30 percent when undetectable, with three-year survival of 24 versus 75 percent. The finding was the strongest independent prognostic factor.
- Three-year relapse 82 percent vs 30 percent by blood NPM1 status after course two.
- Three-year overall survival 24 percent vs 75 percent.
Molecular monitoring of NPM1 now decides whether a patient with otherwise favourable-risk disease should go to transplant in first remission, and molecular relapse can be treated pre-emptively.
- Requires a standardised quantitative PCR assay and defined thresholds.
- Studied under intensive chemotherapy; thresholds under venetoclax regimens are being established.