SOHO 2018 | Addition of gemtuzumab ozogamicin to FLAG-IDA for induction therapy for patients with acute myeloid leukemia

At the 6^th Annual Meeting of the Society of Hematologic Oncology, Alan K. Burnett, from Blackwaterfoot, Isle of Arran, presented an educational talk on “Should We GO to FLAG-Ida?”.¹

In recent years, efforts have been made to improve the standard 7+3 induction chemotherapy regimen for patients with acute myeloid leukemia (AML). The addition of a third drug such as cladribine, gemtuzumab ozogamicin (GO), a fludarabine/cytosine arabinoside (ara-C)/granulocyte-colony stimulating factor (G-CSF) and idarubicin (FLAG-Ida) to the standard regimen has been one of the ways explored.

In a randomized phase III study, the addition of purine analogs, cladribine or fludarabine to standard induction regimen (daunorubicin and cytarabine) was evaluated in adult patients with AML. Data from this study, published in the Journal of Clinical Oncology in 2012, showed that the addition of cladribine, but not fludarabine, to standard induction regimen was associated with an increased rate of complete remission (CR) and an improved survival in adult patients with AML.²

In addition, the phase III AML15 trial assessed three chemotherapy drug combinations including ara-C, daunorubicin and etoposide (ADE), daunorubicin and ara-C (DA) and FLAG-Ida with or without GO in younger patients with untreated AML. In this study, patients were randomly assigned to receive two induction courses of DA or ADE versus FLAG-Ida. Overall remission rates were similar in all groups. FLAG-Ida led to a high CR rate after course 1 and significantly reduced relapse and improved relapse-free survival.³

The prospective phase III AML17 trial assessed the safety and efficacy of daunorubicin combined with clofarabine (DClo) compared with FLAG-Ida in patients with high-risk AML. The main objectives of the study were the number of patients delivered to transplant and overall survival (OS). There was no significant difference in the number of patients delivered to transplant in both the DClo and FLAG-Ida arms. However, FLAG-Ida led to a better OS in patients than DClo thus indicating that FLAG-Ida was superior in patients with high-risk AML.⁴

The speaker then focused on GO, an antibody-drug conjugate (ADC). GO is an antibody-targeted chemotherapeutic agent consisting of a humanized murine CD33 antibody. The speaker noted that FLAG-Ida and GO are two options that can be considered as replacements for the 40-year old, 3+7. Both FLAG-Ida and GO is that they are “both feasible and both contribute to a better quality of remission on the grounds of patients in CR after one induction course and a reduction in relapse risk.”

The combination of GO and FLAG-Ida in patients have been assessed in the phase III AML 15 trial. Of patients enrolled in the phase III study, 80 patients received FLAG-Ida and GO (3 mg/m² on day 1). The results of the study showed that the combination of GO and FLAG-Ida appears to be a feasible option. However, FLAG-Ida was associated with myelosuppression.²

The UK NCRI AML19 trial is assessing FLAG-Ida in patients also receiving GO (3 mg/m²) on day 1 or day 1 & 4 of the first induction course.