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AML1/ETO Fusion: Favoring IC Over VEN/HMA in AML

April, 04, 2024 | AML (Acute Myeloid Leukemia), Leukemia

KEY TAKEAWAYS

  • The study aimed to investigate the impact of AML1/ETO fusion on the efficacy of venetoclax in treating patients with AML.
  • Researchers noticed that frontline VEN/HMA treatment showed a poor response in AML1/ETO-positive AML, favoring IC over VEN/HM.

AML1/ETO fusion confers a favorable prognosis in acute myeloid leukemia (AML) treated with intensive chemotherapy (IC). However, the impact of AML1/ETO fusion on the efficacy of venetoclax in treating AML is unclear.

Dian Jin and the team aimed to assess the efficacy of venetoclax-based therapy in AML1/ETO-positive AML, highlighting its impact on treatment decisions for this subgroup of patients.

They performed an inclusive analysis on patients with newly diagnosed AML in 2 centers, dividing them into 3 cohorts: AML1/ETO-positive AML treated with frontline VEN/HMA (Cohort A), AML1/ETO-negative AML treated with frontline VEN/HMA (Cohort B), or AML1/ETO-positive AML treated with frontline IC (Cohort C). The response and survival were compared between the cohorts.

About 260 patients were included in the study. Patients in Cohort A exhibited a significantly lower overall response rate (ORR) than Cohort B (40.9% vs 71.2%, P = 0.005). The median event-free survival (EFS) in Cohort A and Cohort B was 2.7 months and 7.7 months, respectively, with no significant difference. Cohort C demonstrated significantly superior ORR (80.8%) and median EFS (14.9 months) compared to Cohort A.

These advantages remained significant after propensity score matching. KIT-mutated patients with AML1/ETO-positive AML receiving VEN/HMA had markedly inferior ORR and EFS compared to KIT wild-type patients (ORR 0.0% vs 81.8%, P = 0.001; EFS 1.2 months vs not reached, P < 0.001).

The study concluded that newly diagnosed AML patients with AML1/ETO fusion exhibited a poor response to frontline VEN/HMA treatment. When determining induction therapy for patients with AML1/ETO-positive AML, intensive chemotherapy (IC) should be preferred over VEN/HMA.

The study was sponsored by the National Natural Science Foundation of China, the Natural Science Foundation of Zhejiang Province, and the Key Research and Development Project of Zhejiang Province.

Source: https://pubmed.ncbi.nlm.nih.gov/38466536/

Jin D, Chen H, He J, et al. (2024). “Impact of AML1/ETO Fusion on the Efficacy of Venetoclax Plus Hypomethylating Agents in Newly Diagnosed Acute Myeloid Leukemia.” Target Oncol. 2024 Mar;19(2):237-249. doi: 10.1007/s11523-024-01039-y. Epub 2024 Mar 11. PMID: 38466536; PMCID: PMC10963532.

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