The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia

Abstract

On February 22, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product gemtuzumab ozogamicin (Mylotarg; Pfizer, New York City, NY), intended for the treatment of acute myeloid leukemia. Mylotarg was designated as an orphan medicinal product on October 18, 2000. The applicant for this medicinal product was Pfizer Limited (marketing authorization now held by Pfizer Europe MA EEIG). The demonstrated benefit with Mylotarg is improvement in event‐free survival. This has been shown in the pivotal ALFA‐0701 (MF‐3) study. In addition, an individual patient data meta‐analysis from five randomized controlled trials (3,325 patients) showed that the addition of Mylotarg significantly reduced the risk of relapse (odds ratio [OR] 0.81; 95% CI: 0.73–0.90; p = .0001), and improved overall survival at 5 years (OR 0.90; 95% CI: 0.82–0.98; p = .01) [Lancet Oncol 2014;15:986–996]. The most common (>30%) side effects of Mylotarg when used together with daunorubicin and cytarabine are hemorrhage and infection. The full indication is as follows: “Mylotarg is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33‐positive acute myeloid leukemia (AML), except acute promyelocytic leukemia (APL).” The objective of this article is to summarize the scientific review done by the CHMP of the application leading to regulatory approval in the European Union. The full scientific assessment report and product information, including the Summary of Product Characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu). Implications for Practice This article reflects the scientific assessment of Mylotarg (gemtuzumab ozogamicin; Pfizer, New York City, NY) use for the treatment of acute myeloid leukemia based on important contributions from the rapporteur and co‐rapporteur assessment teams, Committee for Medicinal Products for Human Use members, and additional experts following the application for a marketing authorization from the company. It's a unique opportunity to look at the data from a regulatory point of view and the importance of assessing the benefit‐risk.

Antibody-drug conjugates: the new generation of biotechnological therapies against cancer

“…45 Months later, it was approved by the EMA. 46 Side effects, although less serious, are still reported. 40,45…”

High-Risk Acute Myeloid Leukemia: A Pediatric Prospective

“…This led the FDA in 2016 to reapprove GO in adult patients with de novo AML with favorable and intermediate cytogenetics or relapsed leukemia [ 64 ]. In 2018, the EMA reapproved GO combined with daunorubicin and cytarabine for the treatment of patients aged 15 years and above with previously untreated, de novo CD33-positive AML [ 65 ]. GO was subsequently studied in pediatric clinical trials as treatment for de novo and relapsed patients and demonstrated improvements in EFS and relapse rate when combined with chemotherapy in the favorable and intermediate-risk group [ 66 , 67 ].…”

CD33 Expression and Gentuzumab Ozogamicin in Acute Myeloid Leukemia: Two Sides of the Same Coin

“…In 2017, FDA granted approval of GO with 2 indications: (1) treatment of newly diagnosed CD33-positive AML in adults in combination with DNR and ARA-C at 3 mg/m 2 (up to 5 mg) on days 1, 4, and 7 or as single-agent regimen at 6 mg/m 2 on day 1 and 3 mg/m 2 on Day 8; and (2) treatment of relapsed or refractory CD33-positive AML in adults and in pediatric patients >2 years at 3 mg/m 2 on days 1, 4, and 7 [60,61]. In 2018, EMA approved GO for patients >15 years with previously untreated, de novo CD33-positive AML, at 3 mg/m 2 (up to 5 mg) on days 1, 4, and 7 + DNR 60 mg/m 2 /day on days 1 to 3, and Ara-C 200 mg/m 2 /day by continuous infusion on days 1 to 7 [62,63].…”