FDA Expands Approval of Pfizer’s Mylotarg for Newly Diagnosed CD33-Positive AML in Pediatric Patients Aged ≥1 Month

June 17, 2020 News /Bio ValleyBIOON/ -- The U.S. Food and Drug Administration (FDA) Recently approved expansionPfizerTargeted anticancer drug Mylotarg (gemtuzumab ozogamicin) is indicated for patients aged ≥1 month with newlyDiagnosisCD33-positive acute myeloidLeukemia(AML) patients. The approval was granted through the Priority Review program.

Now, Mylotarg can be used to treat newlyDiagnosisCD33-positive AML (pediatric patients aged ≥1 month and adults), relapsed or refractory CD33-positive AML (pediatric patients aged ≥2 years and adults).

The efficacy and safety of Mylotarg in the pediatric population are supported by data from the AAML0531 (NCT00372593) study, a multicenter, randomized trial that enrolled 1,063 patients aged 0–29 years with newly diagnosedDiagnosisAML patients. In the study, these patients were randomly assigned to receive either five cycles of chemotherapy alone or in combination with Mylotarg (dose 3 mg/m², administered on Day 6 of induction 1 and Day 7 of consolidation 2). The primary efficacy endpoint was event-free survival (EFS), defined as the time from trial initiation to induction failure, relapse, or death from any cause.

Data showed that the hazard ratio (HR) for event-free survival (EFS) with Mylotarg plus chemotherapy combination therapy versus chemotherapy monotherapy was 0.84 (95% CI: 0.71–0.99). In the Mylotarg plus chemotherapy group, the estimated percentage of patients free from induction failure, relapse, or death within 5 years was 48% (95% CI: 43–52%), compared to 40% (95% CI: 36–45%) in the chemotherapy-alone group. There was no difference in overall survival (OS) between the two treatment groups.

The most common ≥ Grade 3 adverse events occurring during Induction 1 and Consolidation 2 in patients treated with MylotargAdverse ReactionsInfection, febrile neutropenia, decreased appetite, hyperglycemia, mucositis, hypoxia, hemorrhage, elevated transaminases, diarrhea, nausea, and hypotension.

Mylotarg is the first CD33-targeted therapy for acute myeloid leukemia (AML). It is an antibody-drug conjugate (ADC) composed of the cytotoxic agent calicheamicin linked to a monoclonal antibody targeting CD33. CD33 is an antigenic protein expressed on AML cells in up to 90% of patients. Upon binding to CD33 antigens on the cell surface, Mylotarg is internalized into the cell, where it releases calicheamicin, leading to cell death.

In the United States, Mylotarg received accelerated approval in 2000 as a monotherapy (high dose) for adult patients with CD33-positive acute myeloid leukemia (AML) who were experiencing their first relapse, were aged ≥60 years, and were not candidates for other cytotoxic chemotherapy. However, in 2010, Pfizer voluntarily withdrew Mylotarg from the U.S. market after a confirmatory trial failed to demonstrate clinical efficacy and showed a higher incidence of fatal toxicity compared with chemotherapy. Nevertheless, Mylotarg remained available in the Japanese market and was provided to patients through a compassionate use program.

Given the unmet medical needs of patients with acute myeloid leukemia (AML), clinicians remain interested in evaluating Mylotarg at different doses and treatment durations. With support from Pfizer, these independent researchers conductedClinical Trial, additional information regarding the efficacy and safety of Mylotarg was obtained.

In September 2017, Mylotarg received U.S.FDAApproval: (1) For newDiagnosisCD33-positive adult patients with AML; (2) pediatric and adult patients aged ≥2 years with CD33-positive, relapsed or refractory AML. (Bioon.com)

Original Source:FDA approves gemtuzumab ozogamicin for CD33-positive AML in pediatric patients