Relapse Rate Decreased With FLAG-Ida Plus Gemtuzumab Ozogamicin in AML

The treatment of newly-diagnosed acute myeloid leukemia (AML) with fludarabine, cytarabine, granulocyte-colony stimulating factor, and idaraubicin (FLAG-Ida) plus gemtuzumab ozogamicin (GO) reduced the incidence of relapse compared with standard induction chemotherapy; however, there was no difference in survival, according to the results of the NCRI AML19 trial published in the Journal of Clinical Oncology.

However, patients with NPM1 or FLT3 mutations demonstrated an improvement in overall survival (OS) with FLAG-Ida plus GO.

The study randomly assigned 1033 patients with newly-diagnosed AML to receive FLAG-Ida plus GO or daunorubicin and Ara-C (DA) Plus GO as induction chemotherapy. All patients received 1 or 2 doses of GO. The primary endpoint was OS. 

At baseline, the majority of patients were aged 40 to 59 and 49% were female. There were 88% of patients with de novo disease, 7% with secondary disease, and 5% with high-risk myelodysplastic syndrome. A FLT3 internal tandem duplication (ITD) or tyrosine kinase domain (TKD) mutation was present among 20% and 7% of patients, respectively, and NPM1 mutations were present among 30%. There were 11% of patients with adverse risk cytogenetics and 12% with core binding factor.

Overall, the objective response rate (ORR) was similar between the FLAG-Ida plus gemtuzumab ozogamicin (93%) and DA plus gemtuzumab ozogamicin (91%) groups after the second cycle (P =.19). The rates of complete remission and complete remission with incomplete hematologic recovery.

The proportion of patients who went on to recieve allogeneic transplant after their first response was similar at 38% with FLAG-Ida plus GO and 42% with DA plus GO (P =.22). However, transplant at any time was higher in the DA plus GO group at 54% compared with 46% in the FLAG-Ida plus GO group (P =.021).

Early mortality rates were similar between the FLAG-Ida plus GO or DA plus GO arms, with 30-day rates of 3.1% and 2.9%, respectively (P =.83), and 60-day rates of 4.3 and 4.6%, respectively (P =.80).

There was no significant difference in the 3-year OS, with a rate of 66% with FLAG-Ida plus GO and 63% with DA plus GO (hazard ratio [HR], 0.92; 95% CI, 0.75-1.13; P =.407). However, the event-free survival rate was higher in the FLAG-Ida plus GO group at 57% compared with 45% in the DA plus GO group (HR, 0.73; 95% CI, 0.61-0.87; P <.001). In addition, the cumulative incidence of relapse in the FLAG-Ida plus GO group was 24% compared with 41% in the DA plus GO group (P <.001).

In a preplanned exploratory subgroup analysis, patients with an NPM1 mutation treated with FLAG-Ida plus GO demonstrated a significant improvement in the 3-year EFS rate at 52.5% compared with 70.2% with DA plus GO. The 3-year OS was also significantly longer at 82% compared with 64% with DA plus GO (HR, 0.5; 95% CI, 0.31-0.81; P =.005).

For patients with FLT3 mutations, OS was also prolonged with FLAG-Ida plus GO with a rate of 64% compared with 54% with DA plus GO (HR, 0.67; 95% CI, 0.45-0.99; P =.047). A second dose of GO did not further improve survival, but was associated with earlier clearance of minimal residual disease.

“Overall, FLAG-Ida plus GO significantly reduced relapse without improving OS,” the authors concluded in their report. “However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS.”

Disclosures: This study was supported in part by a research grant from Jazz Pharmaceuticals. Please see the original reference for a full list of disclosures.

This article originally appeared on Hematology Advisor