In a UK trial (NCRI AML19) reported in the Journal of Clinical Oncology, Russell et al found that intensified induction therapy with FLAG-Ida (fludarabine, cytarabine, granulocyte colony–stimulating factor, and idarubicin) plus gemtuzumab ozogamicin did not improve overall survival in younger patients with newly diagnosed acute myeloid leukemia (AML) vs standard induction with DA (daunorubicin and Ara-C) plus gemtuzumab ozogamicin, although a reduced risk of relapse was observed. An overall survival benefit with intensified induction was observed among patients with NPM1 and FLT3 mutations.
Study Details
In the multicenter trial, 1,479 patients with no known adverse-risk cytogenetics were randomly assigned between November 2015 and November 2020 to receive induction with FLAG-Ida (n = 738) or DA (n = 741); 1,033 patients from the two groups were randomly assigned to receive one or two doses of gemtuzumab ozogamicin. Most patients were aged 60 or younger, but 149 (14%) were older than age 60; all were considered fit for intensive therapy. The primary endpoint was overall survival.
Key Findings
Few differences in any outcomes were observed between receipt of one vs two doses of gemtuzumab ozogamicin.
No difference was observed in the rate of complete remission or complete remission with incomplete hematologic recovery after two courses of FLAG-Ida plus gemtuzumab ozogamicin vs DA plus gemtuzumab ozogamicin (93% vs 91%). No differences in 30-day (2.9% vs 3.1%, P = .83) or 60-day mortality (4.6% vs 4.3%, P = .80) were observed.
No difference in 3-year overall survival was observed (66% vs 63%, P = .41). The FLAG-Ida plus gemtuzumab ozogamicin group had a lower risk of relapse at 3 years (24% vs 41%, P < .001) and improved 3-year event-free survival (57% vs 45%, P < .001). Overall survival was improved with FLAG-Ida plus gemtuzumab ozogamicin among patients with an NPM1 mutation (82% vs 64%, P = .005) and among those with a FLT3 mutation (64% vs 54%, P = .047).
Fewer transplantations were performed in the FLAG-Ida plus gemtuzumab ozogamicin group (238 vs 278, P = .02).
Among patients with vs without core binding factor AML, no significant 3-year overall survival benefit was observed with FLAG-Ida plus gemtuzumab ozogamicin. The best 3-year overall survival rate among patients with core binding factor was observed with DA plus one dose of gemtuzumab ozogamicin (96%).
The investigators concluded: “Overall, FLAG-Ida [plus gemtuzumab ozogamicin] significantly reduced relapse without improving overall survival. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in overall survival. By contrast, in patients with core binding factor AML, outcomes were excellent with DA plus gemtuzumab ozogamicin, with no FLAG-Ida benefit.”
Nigel H. Russell, MD, of the Department of Haematology, Guy’s and St Thomas’ Hospitals NHS Trust, London, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Cancer Research UK and Jazz Pharmaceuticals. For full disclosures of the study authors, visit ascopubs.org.
