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The addition of a monoclonal antibody — called gemtuzumab — combined with standard chemotherapy, has shown significant reduction to the risk of relapse and increased rates of disease-free survival in children with acute myeloid leukemia (AML).
The study evaluated a total of 1,022 children averaging 10 years old at trial sites nationwide. It was led by Alan Gamis, MD, MPH, Associate Division Director, Section of Oncology at Children's Mercy Hospital in Kansas City.
Gemtuzumab was removed from the U.S. market in 2010 because the U.S. Food and Drug Administration felt the potential risks of the drug outweighed its potential benefits. Recent research has raised questions about whether that action was premature. This data supports recent findings in adults with AML that gemtuzumab reduced their risk of relapse when added to a standard chemotherapy regimen.
In the study, patients were treated with either gemtuzumab or a standard regimen. Comparing the two regimens, the addition of gemtuzumab was associated with better disease-free survival (61 vs. 55%) and reduced relapse risk (33 vs. 41%). However, it did not significantly improve overall survival (74 vs. 70%).
Chat Live with Dr. Gamis
Dr. Gamis will discuss this study and answer questions about pediatric oncology from medical professionals, media and the public via Twitter at 1 p.m. Central (2 p.m. Eastern) on Friday, Dec. 20, through the @ChildrensMercy account. Join the conversation by including #cancerchat and @ChildrensMercy in tweets.
Objective: To determine if the addition of GO to standard chemotherapy improves EFS in pediatric AML.
Methods: Patients < 30 years of age were randomly assigned to receive standard therapy alone (noGO) or to receive two doses of GO 3 mg/m2/dose on day 6 of Induction I (IndI) and on day 7 of Intensification II (IntII) in a 5 cycle chemotherapy backbone previously piloted by COG (Cooper et al, Cancer 2012). Use of stem cell transplant (SCT) was stratified by overall risk group assignment (based on cytogenetics, FLT3-ITD high allelic ratio (HAR), and IndI response) in which high risk patients were allocated to best allogeneic donor SCT after Int I, low risk (LR) patients received chemotherapy only, and intermediate risk (IR) were assigned to SCT if there was a matched family donor (MFD).
Results: Between 2006-2010, 1022 of 1070 enrolled non-DS pts were eligible for analysis; characteristics are presented in Table 1. Median follow-up was 3.6 (range 0-6.4) years for those alive.
Protocol therapy was well tolerated with a TM of 2% in induction and 5% overall with no difference by study arm. VOD was observed in 3% (severe in 0.6%) with no difference by study arm. From time of enrollment, GO was significantly associated with better overall EFS (hazard ratio (HzR) 0.83 (95% CI: 0.7-0.99; p=.04) and relapse-free survival (HzR 0.74 (0.6-0.93; p=.01)) whereas OS was not significantly improved (HzR 0.91 (0.74-1.13)). At 3 yr, noGO v GO EFS was 47 v 53%, p=.05 and OS was 65 v 69%, p=.18. In multivariate analyses, GO was significantly associated with improved EFS than standard therapy after adjustment for significant adverse risk factors: age <2yr, initial WBC>100,000x109/L, and black race. GO was not associated with significantly better induction complete remission (CR) when compared to standard therapy (88% v 85%; p=NS). Table 2 illustrates the overall results by randomized arm and by overall risk group from time of CR showing a consistent reduction in relapse risk in all risk groups. Further risk group analysis found several unique results. In the LR group, relapse rates (RR) trended lower in the GO arm but the benefit was reduced by TM during Int 2 & 3 that was significantly worse in the GO arm (3 v 10%, p=.02). In the IR group, EFS, RR, and OS trended towards improvement with GO. However when pts were censored at the time of SCT (as treated), the outcomes were not significantly different between arms (log-rank p=.14 EFS and p=.81 OS). Table 1 shows an imbalance for SCT received in assigned IR pts with fewer actually receiving SCT in the noGO arm. As such, Table 2 shows outcomes by intent-to-treat for IR pts with MFD censored and by as treated for IR pts receiving MFD SCT. Noteworthy in the IR group alone who did receive a SCT, GO arm pts had a significantly better DFS than the noGO arm (intent to treat: p=.022; as treated: p=.044). However, for the IR pts randomized to the noGO arm, SCT failed to provide benefit. For HR pts achieving CR they as well trended towards better survival & RR in the GO arm.
Table 2: Outcomes by randomized treatment assignment following CR
* - ≤.1; + - ≤.01; ^ - intent-to-treat; & - as treated from end of Int 1
Conclusion: GO improves EFS in children, adolescents and young adults with AML by reducing the risk of relapse among those achieving remission.
1Division of Hematology/Oncology/Bone Marrow Transplantation, Children's Mercy Hospitals and Clinics, Kansas City, MO
Disclosures: Off Label Use: Gemtuzumab, when available at the time of the study, had an approved label indication for use in older adult patients with refractory AML.
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