FLAG-Ida Combined with Gemtuzumab Ozogamicin Improves EFS in Younger Patients with Newly Diagnosed AML

By Leah Sherwood - Last Updated: December 27, 2022

Gemtuzumab ozogamicin (GO) combined with the induction regimen FLAG-Ida (fludarabine, cytosine arabinoside, idarubicin, and granulocyte colony-stimulating factor) significantly improved event-free survival (EFS) in younger patients with newly diagnosed acute myeloid leukemia (AML) compared to daunorubicin and cytosine arabinoside combined with GO, according to the UK NCRI AML19 trial.

The investigators, led by Nigel H. Russell, MD, of Guy’s and St Thomas’ National Health Service Foundation Trust in London, also reported no benefit was observed in a fractionated GO schedule in the large, randomized comparison.

The results were presented at the 2022 American Society of Hematology Annual Meeting and Exposition in a poster session.

The trial randomized 1,475 patients (median age, 51.5 years) with newly diagnosed AML or myelodysplastic syndromes-excess blasts-2 to receive FLAG-Ida (n=738) or daunorubicin plus cytosine arabinoside (n=737).

Among these patients, 1,031 were also randomized to receive a single dose of GO (3 mg/m2 on day one; n=513) or a fractionated schedule (maximum 5 mg on days one and four; n=518).

The median follow-up was 32 months. Complete remission/complete remission with incomplete hematologic recovery was 91% for daunorubicin and cytosine arabinoside plus GO and 93% for FLAG-Ida plus GO and did not differ by GO dose. EFS was significantly better with FLAG-Ida plus GO compared to daunorubicin and cytosine arabinoside plus GO (hazard ratio [HR], 0.73; CI, 0.61-0.87; P<.001), but there was no difference in overall survival (OS; HR, 0.92; CI, 0.75-1.13;  P=.41).

Fewer transplants were performed in the FLAG-Ida plus GO arm overall (n=237; 46% compared to the daunorubicin and cytosine arabinoside plus GO cohort (n=278; 54%), reflecting the application of minimal residual disease (MRD) negativity to guide transplant decisions and the reduced relapse risk with FLAG-Ida, the investigators reported.

Although there was no OS benefit for FLAG-Ida plus GO, there was evidence of an OS benefit in major subgroups, including patients with NPM1 and FLT3 mutations, the authors noted. This finding was supported by MRD analysis that showed a reduction in NPM1 MRD positivity after two courses of FLAG-Ida plus GO. Furthermore, this survival benefit with FLAG-Ida plus GO was associated with a reduction in the requirements for transplant in first complete remission and overall.

“Given the benefit observed in FLT3-mutated AML in the absence of a FLT3 inhibitor, studies combining FLAG-Ida [plus] GO with Midostaurin are warranted,” the authors concluded.


Russell NH, Wilhelm-Benartzi C, Knapper S, et al. FLAG-Ida combined with gemtuzumab ozogamicin (GO) Improves event free survival in younger patients with newly diagnosed acute myeloid leukaemia (AML) and shows an overall survival benefit in NPM1 and FLT3 mutated subgroups. Results from the UK NCRI AML19 trial. Abstract #218. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.

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