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Prognostic impact of co-mutations in patients with IDH1/2-mutated AML
IDH1 or IDH2 (IDH1/2) mutations occur in 11–20% of adults with acute myeloid leukemia (AML). Prognoses for patients with IDH1/2-mutated (IDH1/2m) AML can be affected by further co-mutations. Lai et al. published a retrospective analysis in Blood Science, assessing the impact of co-mutations in patients with newly diagnosed IDH1/2-mutated AML who had received intensive chemotherapy (N = 118) on overall survival, relapse-free survival, and cumulative incidence of relapse.
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Key learnings |
NPM1m was associated with favorable OS (p = 0.019 by univariate analysis), particularly in the absence of DNMT3A or FLT3-ITD mutations (3-year OS, 96.3% or 86.3%, respectively, by multivariate regression analysis). |
DNMT3Am was associated with poor prognosis (3-year OS, 52.0%; 3-year RFS, 44.8%; 3-year CIR, 42.6%), including in MRD– AML following two chemotherapy courses. DNMT3Am and MRD positivity were independent adverse risk factors for OS, RFS, and CIR in multivariate regression. |
HSCT in CR1 significantly improved RFS (HR, 0.23; p = 0.015), with a trend towards improved OS in patients with DNMT3Am AML, but with no observed benefit in those with favorable genotypes such as IDH1/2m NPM1m DNMT3Awt or IDH1/2m NPM1m FLT3-ITDwt. |
These results highlight DNMT3Am, MRD status, and the IDH1/2m NPM1m DNMT3Awt/FLT3-ITDwt genotypes as prognostic factors in AML, providing a reference for risk stratification for patients with co-mutations in AML. |
AML, acute myeloid leukemia; CIR, cumulative incidence of relapse; CR1, first complete remission; DNMT3Am, mutated DNMT3A; FLT3-ITDm; mutated FLT3-ITD; HSCT, hematopoietic stem cell transplantation; IDH1/2m, mutated IDH1/2; MRD, measurable residual disease; NPM1m, mutated NPM1; OS, overall survival; RFS, relapse-free survival; wt, wild type.
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When treating a patient newly diagnosed with IDH1-mutated AML who is ineligible for intensive chemotherapy, which initial treatment approach would you most likely consider?
