This article is more than 5 years old. Information may no longer be current.
Addition of gemtuzumab ozogamicin to chemotherapy improved EFS, prevented relapse in pediatric AML
NEW ORLEANS — The addition of gemtuzumab ozogamicin to standard chemotherapy prolonged EFS and reduced the risk for relapse in children, adolescents and young adults with acute myeloid leukemia, according to study results presented at the ASH Annual Meeting and Exhibition.
“The finding that targeted anti-CD33-linked chemotherapy reduces the risk of relapse with potentially manageable toxicity adds another pathway of therapy to the management of patients with AML,” lead study author Alan S. Gamis, MD, MPH, of Children’s Mercy Hospitals and Clinics in Kansas City, Mo., told HemOnc Today.
The study included 1,022 eligible patients younger than 30 years. Gamis and colleagues assigned 511 patients to standard chemotherapy and 511 to standard chemotherapy plus gemtuzumab ozogamicin (Mylotarg, Wyeth).
There were significantly more patients at high cytogenetic risk in the standard therapy arm than the gemtuzumab ozogamicin arm (26 vs. 13; P<.01). The median age of the patients was 9.5 years in the standard therapy arm vs. 9.9 years in the treatment arm.
Patients assigned to gemtuzumab ozogamicin received two 3 mg/m2 doses, one on day 6 of the first induction cycle and another on day 7 of the second intensification cycle of a five-cycle chemotherapy regimen.
Median follow-up was 3.6 years (range, 0-6.4) for survivors.
Overall, patients who received gemtuzumab ozogamicin demonstrated significantly improved EFS (HR=0.83; 95% CI, 0.7-0.99) and RFS (HR=0.74; 95% CI, 0.6-0.93) than patients who received standard therapy alone.
Gamis and colleagues observed no significant differences in OS between the treatment arms (HR=0.91; 95% CI, 0.74-1.13).
At 3 years, 53% of patients who received gemtuzumab ozogamicin achieved EFS (P=.05). Three-year OS was higher among those treated with gemtuzumab ozogamicin (69% vs. 65%; P=.18).
After researchers adjusted for significant adverse risk factors — including age younger than 2 years, baseline white blood cell count more than 100,000x109/L and black race — gemtuzumab ozogamicin remained significantly associated with improved EFS.
The improved EFS was seen despite that the treatment was not significantly associated with improved rates for complete remission (88% vs. 85%).
Researchers observed 5% overall toxic mortality while on therapy, with no significant differences among the study arms. Veno-occlusive disease (VOD) was observed in 3% of patients; 0.6% of the cases were severe. There were no differences in VOD between the arms.
Further analyses indicated that patients with low-risk AML treated with gemtuzumab ozogamicin were at lower risk for relapse (20% vs. 30%) compared with those who received standard therapy (HR=0.58; P=.04). However, this benefit decreased in cycles 2 and 3, with an increased rate for toxic mortality in gemtuzumab ozogamicin-treated patients (8% vs. 2%; P=.03).
Patients with intermediate-risk disease who underwent stem cell transplant and received gemtuzumab ozogamicin demonstrated significantly improved DFS compared with those who received chemotherapy alone (intent-to-treat, P=.022; treated, P=.044). Stem cell transplantation did not benefit intermediate-risk patients who did not receive gemtuzumab ozogamicin.
“As AML is a heterogeneous malignancy, further analysis of the recent trials is important to best delineate who are the most appropriate patients who will receive benefit from adding this agent to their therapies,” Gamis said. “Further effort should be put forth to continue investigating this approach, the benefits of which have also been seen in adults, and to eventually make this therapy available to all appropriate patients with AML.”
For more information:
Gamis AS. Abstract #355. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2013; New Orleans.
Disclosure: The researchers report no relevant financial disclosures.