The U.S. Food and Drug Administration’s Oncologic Drugs Advisory Committee (ODAC) issued a favorable opinion of gemtuzumab ozogamicin (GO), a recombinant anti-CD33 drug conjugate, for the treatment of CD33-positive acute myeloid leukemia (AML). (GO was originally approved under the FDA’s accelerated approval program in 2000, but the manufacturer voluntarily withdrew the drug in 2010 following reports of adverse events and failure of the drug to show improvement in complete response rate, disease-free survival, or overall survival when combined with induction and consolidation chemotherapy for younger adults with AML in the Southwest Oncology Group S0106 phase III clinical trial.)
The present recommendation is based on results from the phase III ALFA-0701 trial, in which GO was evaluated as part of combination therapy with daunorubicin for treatment of de novo AML. Patients were randomized 1:1 to receive daunorubicin with or without GO for induction or consolidation therapy.
At three-year follow-up, patients treated with GO appeared to have a higher event-free probability than patients in the daunorubicin-alone arm (39.8% and 13.6%; p value not reported), and the median time to an event was also longer in the GO arm (17.3 months vs. 9.5 months; p value not reported). Median overall survival was slightly higher in the GO arm but did not reach statistical significance (time to event = 27.5 months vs. 21.8 months).
The most common adverse events associated with GO were related to bleeding or infection. Eight patients developed veno-occlusive disease (VOD), six of whom were in the GO arm. The remaining two patients with VOD were randomized to receive daunorubicin but were treated with GO upon relapse.
A final decision on the application status will be made in September.
Source: FDA ODAC Briefing Document, July 11, 2017.