Gemtuzumab Ozogamicin Receives FDA Approval for Acute Myeloid Leukemia Treatment

On September 1, 2017, the United States Food and Drug Administration FDA, for newly diagnosed CD33-positive acute myeloid leukemia (AML) in adult patients, and for recurrent or treatment-resistant CD33-positive AML in pediatric and adult patients aged 2 and older, approved treatment with gemtuzumab ozogamicin (brand name Mylotarg).

Gemtuzumab ozogamicin was approved in 2000 by the FDA for a different patient population at a higher dose and with a different administration schedule. However, in 2010 it was voluntarily withdrawn because benefits in clinical trials could not be confirmed and because of safety concerns (such as early deaths and development of veno-occlusive disease).

According to gemtuzumab ozogamicin’s FDA approval on September 1, it may be used in combination with daunorubicin and cytarabine chemotherapy in newly diagnosed adults with AML, or alone in adult and pediatric patients meeting certain criteria.

Approval of gemtuzumab ozogamicin in combination with chemotherapy for adults is based on a multicenter randomized study in patients aged 50-70, with 271 newly diagnosed patients, randomized (1:1), open-label and phase 3. Patients received daunorubicin 60 mg/m2 on days 1-3 and cytarabine 200 mg/m2 on days 1-7 (n=135), or this chemotherapy with gemtuzumab ozogamicin (n=136) at 3 mg/m2 (up to a maximum of 5 mg) on days 1, 4 and 7.

Estimated mean event-free survival (time until events affecting treatment, such as disease progression or serious side effects) was reported as 17.3 months in patients receiving gemtuzumab ozogamicin and 9.5 months with chemotherapy alone. Single-agent gemtuzumab ozogamicin use is based on two clinical trials. The first was a multicenter study comparing gemtuzumab ozogamicin monotherapy with best supportive care, involving 237 patients, randomized (1:1), open-label and phase 3. It included newly diagnosed AML patients older than 75 or aged 61-75 with performance status above a certain level according to World Health Organization criteria, or patients unwilling to receive intensive chemotherapy. Induction treatment involved gemtuzumab ozogamicin on day 1 at 6 mg/m2 and on day 8 at 3 mg/m2. After induction, patients without disease progression or significant toxicity received gemtuzumab ozogamicin at 2 mg/m2 every 4 weeks, 1 administration per cycle, for up to 8 cycles as continuation treatment. Best supportive care (BSC) included standard palliative supportive care measures and hydroxyurea or other antimetabolites. Estimated mean overall survival was 4.9 months for patients receiving gemtuzumab ozogamicin and 3.6 months for those receiving BSC.

The second study was a single-arm, open-label trial in CD33-positive AML at first recurrence, including 57 patients in a phase 2 trial. Patients received gemtuzumab ozogamicin at 3 mg/m2 on days 1, 4 and 7 as a single course. Consolidation consisted of intravenous cytarabine for 3 days every 12 hours. Fifteen patients achieved a complete response following gemtuzumab ozogamicin treatment. Mean survival from the first documentation of complete response until recurrence or death was 11.6 months.

The most common side effects are bleeding, infection, fever, nausea, vomiting, constipation, headache, increased liver values (ALT, AST), rash and oral infections. Serious side effects (adverse reactions) associated with gemtuzumab ozogamicin are liver toxicity (including veno-occlusive disease), infusion-related reactions (including severe allergic reactions) and bleeding.