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ASH 2025 | Outcomes and patterns of relapse of NPM1-mutated AML treated with venetoclax-based therapies
In this video, Wei-Ying Jen, MA, BM BCh, M Med, MRCP, FRCPath, The University of Texas MD Anderson Cancer Center, Houston, TX, presents an analysis of outcomes and patterns of relapse in patients with NPM1-mutated acute myeloid leukemia (AML) treated with venetoclax-based regimens of varying intensities. Dr Jen suggests that venetoclax-based therapies are likely effective at eradicating NPM1-mutated leukemia, and that relapses may often arise from a different clone. This interview took place at the 67th ASH Annual Meeting and Exposition, held in Orlando, FL.
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Transcript
So in that paper we looked at 3 groups of patients and we chose these 3 groups based on the intensity of therapy. So the least intensive therapy is a doublet of a hypomethylating agent and venetoclax, and then you get this kind of intermediate kind of intensity which is cladribine, low dose cytarabine, and venetoclax, and then we have the most intensive, which is intensive chemotherapy and venetoclax, and that was people who got either FLAG-IDA/VEN or CLIA/VEN...
So in that paper we looked at 3 groups of patients and we chose these 3 groups based on the intensity of therapy. So the least intensive therapy is a doublet of a hypomethylating agent and venetoclax, and then you get this kind of intermediate kind of intensity which is cladribine, low dose cytarabine, and venetoclax, and then we have the most intensive, which is intensive chemotherapy and venetoclax, and that was people who got either FLAG-IDA/VEN or CLIA/VEN. And then we looked only at the NPM1 positive people, which I think were about 20% of the overall cohort, about 100 patients, if memory serves me. and we looked at how they relapsed.
And so just as a background to this, the proportion of NPM1 patients who relapse without NPM1, with just intensive chemotherapy without venetoclax is about 5 to 10%. And so we were quite surprised when we looked at our cohort. the rates of NPM1 wild type relapse were really about 40 to 60%. And so I think, and also one of the other things that we noted was that the more intense the treatment, the higher the rate of NPM1 wild type relapse. We also looked specifically at these relapse, they have a longer lead time to relapse than the NPM1-mutated relapses. and we looked at the immunophenotype by flow cytometry. They appear to be different leukemias. So it looks like the venetoclax-based therapies are effectively curing these NPM1-mutated leukemias, and that the relapses are either, you know, a different clone that was present at the low level of diagnosis or possibly a secondary type AML.
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