FDA Approves Gemtuzumab Ozogamicin for CD33+ Pediatric AML

June 16, 2020
OncLive Staff

The US Food and Drug Administration has extended the indication of gemtuzumab ozogamicin (Mylotarg) for newly diagnosed CD33-positive acute myeloid leukemia to include pediatric patients 1 month and older.

The FDA has extended the indication of gemtuzumab ozogamicin (Mylotarg) for newly diagnosed CD33-positive acute myeloid leukemia (AML) to include pediatric patients 1 month and older.

The decision was supported by data from the multicenter, randomized AAML0531 trial of 1,063 patients with newly diagnosed AML who were between the ages of 0 and 29 years. In the trial, patients were randomized to receive 5-cycle chemotherapy alone or in combination with 3 mg/m2 of gemtuzumab ozogamicin administered once on day 6 in the induction 1 phase of the trial and once on day 7 in the intensification 2 phase.

The primary end point of the trial was event-free survival (EFS), which was measured from trial entry until induction failure, relapse, or death due to any cause. Results showed an EFS hazard ratio of 0.84 (95% CI, 0.71-0.99). At 5 years, the estimated percentage of patients free of induction failure, relapse, or death was 48% (95% CI, 43%-52%) in the gemtuzumab ozogamicin plus chemotherapy arm versus 40% (95% CI, 36%‑45%) in the chemotherapy-alone arm. No difference in overall survival was demonstrated between treatment arms.

With regard to safety, the commonly reported grade 3 or higher toxicities that were reported during the induction 1 and intensification 2 phases in ≥5% of patients who were administered the antibody-drug conjugate (ADC) included infection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, increased transaminase, diarrhea, nausea, and hypotension.

Previously, gemtuzumab ozogamicin was approved by the FDA for use in combination with daunorubicin and cytarabine in adults with newly diagnosed CD33-positive disease and as a single agent for patients aged 2 years and older with CD33-positive, relapsed/refractory disease, based on findings from several trials, including ALFA-0701, AML-19, and MyloFrance-1.1.

The approval of the ADC in combination with chemotherapy was based on results from the multicenter, open-label phase 3 ALFA-0701 trial. In this trial, a total of 271 patients between the ages of 50 and 70 with newly diagnosed AML were randomized to receive daunorubicin and cytarabine alone (n = 136) or combined with the ADC (n = 135), which was given at 3 mg/m2 on days 1, 4, and 7 during induction and day 1 of each of the 2 consolidation chemotherapy courses. The primary end point of the trial was EFS, and the secondary end point was overall survival (OS).

Results showed that treatment with the ADC led to a statistically significant improvement in EFS of 7.8 months. The median EFS in the ADC arm was 17.3 months compared with 9.5 months in the control arm (HR, 0.56; 95% CI, 0.42-0.76; P <.001). However, the drug was not found to result in a significant OS improvement (HR, 0.81; 95% CI, 0.60-1.09; P =.16).

For use as a single agent, the ADC was examined in 2 trials. The first was the open-label, phase 3 AML-19 study, which enrolled patients with newly diagnosed disease who were greater than 75 years of age or aged 61-75 with a WHO performance status of greater than 2 or were unwilling to receive treatment with intensive chemotherapy.

These patients were randomized to receive either the ADC (n = 118) or best supportive care (n = 119). The agent was administered at a higher 6 mg/m2-dose on day 1 and then dropped to 3 mg/m2 on day 8 of treatment. Patients who did not experience progressive disease then went on to receive the ADC at 2 mg/m2 on day 1 every 4 weeks.

Results from this trial indicated that gemtuzumab ozogamicin led to a 31% reduction in the risk of death and a median OS of 4.9 months versus 3.6 months with best supportive care (HR, 0.69; 95% CI, 0.69; 95% CI, 0.53-0.90; 2-sided P =.005).

In the single-arm, open-label, phase 2 MyloFrance-1 study, a total of 27 adult patients with AML were given single-agent gemtuzumab ozogamicin at 3 mg/m2 on days 1, 4, and 7. A total of 15 patients achieved a complete remission with the ADC, with a median relapse-free survival of 11.6 months.

In 2000, the ADC was granted an accelerated approval for the treatment of patients 60 years of age or older with CD33-positive AML who were in first relapse and ineligible for cytotoxic chemotherapy. However, ten years later, in 2010, the drug was voluntarily removed from the market following data from the SWOG-S0106 trial, which failed to show improvement in CR, disease-free survival, or OS with the ADC versus daunorubicin and cytarabine. Data from subsequent studies indicated that if the drug was administered at a lower dose, it could be safely combined with daunorubicin and cytarabine.


  1. FDA approves gemtuzumab ozogamicin for CD33-positive AML in pediatric patients. News release. June 16, 2020. Accessed June 16, 2020. bit.ly/2Y86KRI.
  2. FDA approves gemtuzumab ozogamicin for CD33-positive AML. News release. September 1, 2017. Accessed June 16, 2020. bit.ly/2AK8Ga2.

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