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Characteristics and outcomes in patients with newly diagnosed AML with KMT2Ar: A retrospective study
KMT2A rearrangements (KMT2Ar) occur in around 3–7% of all patients with newly diagnosed acute myeloid leukemia (AML) and are associated with poor outcomes. To further understand the characteristics and outcomes of these patients, Bataller et al. conducted a single-center, retrospective study assessing the impact of intensive therapy (IT) vs low-intensity therapy (LIT) in patients with KMT2Ar AML, and the findings were published in Leukemia. The study included 1,611 patients diagnosed with AML between April 2014 and December 2022, of which 69 (4.3%) harbored KMT2Ar and were treated with IT (n = 41) or LIT (n = 27).
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Key learnings |
Patients with KMT2Ar (n = 25) had a higher incidence of t-AML compared to those without KMT2Ar (n = 246) (36% vs 16%; p < 0.001). NRAS (30%), KRAS (23%), and FLT3 (19%) were the most frequent mutations in patients with KMT2Ar AML. |
The CR/CRi rate was 81% and 100% in patients treated with IT (n = 21) and IT + Ven (n = 20), respectively, and 33% and 61% in those treated with LIT (n = 9) and LIT + Ven (n = 18), respectively. |
Furthermore, 5-year survival rates were higher in patients who received IT (OS, 64%; EFS, 62%) compared with those who received LIT (OS, 7%; EFS, 7%). |
Multivariate analysis demonstrated that in patients treated with LIT, KRAS/NRAS mutations were predictors of worse OS (HR, 2.93; 95% CI, 1.18–7.29; p = 0.021) and EFS (HR, 3.51; 95% CI, 1.35–9.24; p = 0.01). |
The findings suggest improved outcomes in patients with KMT2Ar AML treated with IT, potentially reflecting advances in treatment and assessment criteria. The poor outcomes associated with LIT indicated a need for novel therapy combinations in this patient population. |
AML, acute myeloid leukemia; CI, confidence interval; CR, complete remission; CRi, complete remission with incomplete blood count recovery; EFS, event-free survival; HR, hazard ratio; IT, intensive therapy; LIT, low-intensity therapy; MRD, measurable residual disease; OS, overall survival; t-AML, therapy-related AML; Ven, venetoclax.
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