NEW ORLEANS—Adding gemtuzumab ozogamicin to standard chemotherapy improved event-free survival (EFS) by reducing relapse risk in children with de novo acute myeloid leukemia (AML), results from a phase 3 Children’s Oncology Group (COG) trial reported at the 55th American Society of Hematology Annual Meeting and Exposition.

Escalation of treatment intensity for childhood AML has improved EFS, but with limits, including a high toxic mortality of 10% to 19% and risk of sequelae, including congestive heart failure. For these reasons, “alternatives other than further intensification are needed,” said Alan S. Gamis, MD, MPH, of the Children’s Mercy Hospitals and Clinics, Kansas City, MO.

Between 2006 and 2010, the COG trial AAML0531 randomly assigned 1,070 patients younger than 30 years of age to standard therapy or to standard therapy plus two doses of gemtuzumab ozogamicin 3 mg/m2/dose on day 6 of Induction I (IndI) and on day 7 of Intensification II (IntII) in a five-cycle chemotherapy backbone.

Continue Reading

Use of stem cell transplant (SCT) was stratified by overall risk group assignment (based on cytogenetics, FLT3-ITD high allelic ratio, and IndI response), in which high-risk patients were allocated to best allogeneic donor SCT after Int I, low-risk patients received chemotherapy only, and intermediate-risk patients were assigned to SCT if there was a matched family donor.

Median follow-up was 3.6 years (range, 0-6.4 years) for those alive. Of the 1,022 patients included in the analysis, median age was 9.5 years (range, 0-29 years) in the standard therapy alone arm (n=511) and 9.9 years (range, 0-29 years) in the gemtuzumab ozogamicin arm (n=511). Baseline characteristics were matched for cytogenetic and overall risk groups. Significantly fewer patients in the intermediate-risk group received SCT as assigned in the arm without versus with gemtuzumab ozogamicin (73% vs. 92%; P< 0.01).

Protocol therapy was well tolerated: toxic mortality was 2% in induction and 5% overall, with no difference by study arm, Dr. Gamis reported. “Veno-occlusive disease was observed in 3% (severe in 0.6%), with no difference by study arm.”

From study entry among all risk groups, gemtuzumab ozogamicin was significantly associated with better EFS (hazard ratio [HR], 0.83; 95% CI: 0.70-0.99; P=0.04) and relapse-free survival (HR, 0.74; 95% CI: 0.6-0.93; P=0.01), whereas overall survival (OS) was not significantly improved (HR, 0.91; 95% CI: 0.73-1.12; P 0.36).

At 3 years, EFS in the arm without gemtuzumab ozogamicin was 46.9% versus 53.1% for the arm that included gemtuzumab ozogamicin; OS was 65.4% versus 69.4%, respectively.

“In multivariate analyses, gemtuzumab ozogamicin was significantly associated with improved EFS than standard therapy after adjustment for significant adverse risk factors, age [younger than] 2 years, initial WBC > 100,000×109/L, and black race,” Dr. Gamis said.

Gemtuzumab ozogamicin was not associated with significantly better induction complete remission when compared with standard therapy (88% vs. 85%; P = not significant); rather, a consistent reduction in relapse risk was observed in all risk groups.

Outcome differences between arms by risk group after induction found that in the low-risk group, who received chemotherapy only, relapse rates trended lower in the arm with versus without gemtuzumab ozogamicin  (30.3% vs. 19.7%; HR, 0.58; 95% CI: 0.34-0.97) but the benefit was reduced by toxic mortality during Int 2 and 3 that was significantly worse in the gemtuzumab ozogamicin arm (7.5% vs. 1.8%; HR, 4.39; 95% CI: 0.95-20.4; P = 0.02); all were infection related.

In the intermediate-risk group, who received chemotherapy or SCT, no significant differences were observed between the two arms, although the SCT recipients had reduced response rates. In the high risk group, among patients who had received SCT only, trends were observed in the gemtuzumab ozogamicin arm with respect to reduced response rates (27% vs. 44.8%; HR, 0.53; 95% CI: 0.25-1.09), improved disease-free survival (55.9% vs. 40.3%; HR, 0.66; 95% CI: 0.37-1.18), and improved OS (67.5% vs. 48.5%; HR, 0.61; 95% CI: 0.32-1.16).

Although gemtuzumab ozogamicin was removed from the market due to lack of clinical value in earlier trials, “this growing body of positive data in populations of critical need may be sufficient to bring it back as a commercial treatment option,” Dr. Gamis said. When available at the time of the study, gemtuzumab ozogamicin had an approved label indication for use in older adult patients with refractory AML.


  1. Aplenc R et al. Abstract #615. Presented at: American Society of Hematology Meeting 2013. Dec. 7-10, 2013; New Orleans.