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Adding Gemtuzumab Ozogamicin to Chemotherapy Improves Event-Free Survival but Not Overall Survival in Children and Adolescents With De Novo AML

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Key Points

  • The addition of gemtuzumab ozogamicin to chemotherapy improved 3-year event-free survival but not overall survival.
  • A post hoc analysis showed a significant reduction in risk of relapse after induction.

In a Children’s Oncology Group phase III trial reported in the Journal of Clinical Oncology, Gamis et al found that the addition of gemtuzumab ozogamicin (Mylotarg), an immunoconjugate targeting CD33, resulted in significantly prolonged event-free survival but not overall survival when added to standard chemotherapy in children and adolescents with de novo acute myeloid leukemia (AML).

Gemtuzumab ozogamicin received accelerated approval in 2000 on the basis of single-agent efficacy, but the drug was voluntarily withdrawn in 2010 after a confirmatory trial (Southwest Oncology Group S0106) showed no improvement in the primary endpoints of remission induction and safety. However, interest in the drug remains on the basis of concurrent randomized trials in adults showing reduced risk of relapse in low- and intermediate-risk AML.

Study Details

In the trial, patients 1,122 patients aged 0 to 29 years with newly diagnosed AML were randomly assigned to receive standard five-course chemotherapy alone (n = 511) or the same chemotherapy plus two doses of gemtuzumab ozogamicin  (3 mg/m2/dose) given once in induction course 1 and once in intensification course 2 (n = 511). The primary endpoints were event-free survival and overall survival from study entry.

Improved Event-Free Survival, Not Overall Survival

Among all patients, event-free survival from study entry was significantly improved in the gemtuzumab ozogamicin group (3-year event-free survival = 53.1% vs 46.9%, hazard ratio [HR] = 0.83, P =.04), with nonsignificant reductions observed in the low-risk (71.4% vs 64.0%,  HR = 0.74, P = .18) and intermediate-risk subgroups (51.4% vs 45.8%, HR = 0.82, P = .09) but not in the high-risk subgroup (31.2% vs 27.2%, HR = 1.01, P = .96).

Overall survival was not improved in the gemtuzumab ozogamicin group (3-year overall survival = 69.4% vs 65.4%, HR = 0.91, P = .39), with no differences observed in the low-risk (HR = 1.11, P = .74), intermediate-risk (HR = 0.83, P = .19), or high-risk subgroups (HR = 1.06, P = .78).

Lower Relapse Rate

There was no difference between groups in remission rate (88% vs 85%, P = .15). A post hoc analysis of outcome from the end of induction course 2 found that risk of relapse at 3 years was reduced in the gemtuzumab ozogamicin group (32.8% vs 41.3%, HR = 0.73, P = .006), risk of treatment-related mortality was nonsignificantly increased (6.6% vs 4.1%, HR = 1.69, P = .08), and 3-year disease-free survival was nonsignificantly increased (60.6% vs 54.7%, HR = 0.82, P = .07). There was no difference between groups in 3-year overall survival from the end of induction.

The investigators concluded: “[Gemtuzumab ozogamicin] added to chemotherapy improved [event-free survival] through a reduction in [relapse rate] for children and adolescents with AML.”

Alan S. Gamis, MD, MPH, of Children’s Mercy Hospitals and Clinics, Kansas City, Missouri, is the corresponding author for the Journal of Clinical Oncology article.

The study was supported by a grant from the National Cancer Institute. The study authors reported no potential conflicts of interest.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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