FLAG-Ida plus venetoclax induces high MRD-negativity rates in AML

Treatment with fludarabine plus cytarabine, idarubicin and granulocyte colony-stimulating factor (FLAG-Ida) chemotherapy plus venetoclax led to high measurable residual disease (MRD) negativity rates across the European LeukaemiaNet (ELN) subgroups in participants with newly diagnosed acute myeloid leukaemia (AML). Results showed that FLAG-Ida plus venetoclax may also be an efficacious salvage therapy for participants with relapsed/refractory (RR) AML.

The current phase 2 trial (NCT03214562) assessed the efficacy and safety of FLAG-Ida plus venetoclax in 127 participants with newly diagnosed (n=68) or RR AML (n=59). The primary outcome was the objective response rate (ORR) defined by the ELN. Dr Wei-Ying Jen (MD Anderson Cancer Center, TX, USA) presented the results [1].

In the participants with newly diagnosed disease, the ORR was 99% and MRD negativity (10^-4) was reported in 89%. These findings were consistent across ELN risk groups. The 2-year overall survival (OS) rate was 75% (see Figure). Notably, those who received stem cell transplantation in their first clinical remission had a survival benefit over those who did not proceed to stem cell transplantation. In contrast, the ORR was 70% in participants with RR AML and the 2-year OS rate was 40% in this subgroup. “Participants with TP53 wild-type disease appeared to respond better to this therapy,” added Dr Jen.

Figure: Overall survival with FLAG-IDA plus venetoclax in participants with newly diagnosed and relapsed/refractory AML [1]



CI, confidence interval; d, day; mut, mutant; NE, not estimable; OS, overall survival; S1, in first salvage; S2, in second salvage; WT, wild-type.

As for safety, infections were the most common adverse events. Infections of grade 3 or higher occurred in 80% of the participants, and gastrointestinal toxicity or bleeding was documented in 16% of participants with newly diagnosed AML and 7% of those with RR AML.

In conclusion, FLAG-Ida plus venetoclax was associated with high MRD-negativity rates in newly diagnosed participants with AML. It also appeared to be an efficacious salvage treatment for participants with RR AML, especially those with TP53 wild-type disease.

1. Jen W-Y, et al. FLAG-IDA + venetoclax in newly diagnosed or relapsed/refractory AML. S136, EHA congress 2024, 13–16 June, Madrid, Spain.

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Posted on 12 August 202412 August 2024