Low-Dose Gemtuzumab Ozogamicin Benefited Older AML Patients

Older patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy achieved improved overall survival when assigned to low-dose gemtuzumab ozogamicin compared with patients treated with best supportive care, according to the results of the phase III EORTC-CIMEMA AML-19 trial.

“These findings suggest that single-agent gemtuzumab ozogamicin could represent a new option for this patient group,” wrote researcher Sergio Amadori, MD, of the Tor Vergata University Hospital in Italy, and colleagues in the Journal of Clinical Oncology. “These results, which add to the mounting evidence that withdrawal of gemtuzumab ozogamicin from the market in 2010 (due to lack of benefit and increased toxicity in a phase III trial) was premature, support further investigations of gemtuzumab ozogamicin in combination with other novel agents in this patient population of high unmet need.”

According to background information in the study, intensive chemotherapy in older patients with AML yields only a marginal benefit and small chance at a cure. Therefore, these patients are typically treated with best supportive care including hydroxyurea. In 2000, gemtuzumab ozogamicin was approved by the US Food and Drug Administration to treat relapsed AML in older patients who could not undergo intensive chemotherapy, but studies of its use in newly diagnosed older patients have had disappointing results.

In this phase III trial, Amadori and colleagues studied fractionated lower doses of gemtuzumab ozogamicin. Between 2004 and 2013, the study randomly assigned patients to a single induction course of gemtuzumab ozogamicin (6 mg/m² on day 1 and 3 mg/m² on day 8; n = 118) or best supportive care including hydroxyurea (n = 119). Any patient that did not progress after induction with gemtuzumab ozogamicin could receive up to eight monthly infusions at 2 mg/m². The median age of patients was 77.

By data cutoff in 2014, 95.8% of patients assigned gemtuzumab ozogamicin and 96.6% of patients assigned best supportive care had died. Patients assigned to gemtuzumab ozogamicin had a median overall survival of 4.9 months compared with 3.6 months for patients in the best supportive care group (hazard ratio [HR], 0.69; 95% CI, 0.53–0.90; P = .005). At 1 year, 24.3% of patients assigned gemtuzumab ozogamicin were alive compared with 9.7% of patients assigned best supportive care.

“Exploratory subgroup analyses revealed no interaction between baseline patient characteristics and treatment effect for overall survival, with the exception of CD33 expression status, sex, and cytogenetic profile,” the researchers wrote.

Women assigned gemtuzumab ozogamicin had a significantly improved HR for overall survival (HR, 0.53; 95% CI, 0.35–0.79); whereas, men did not. In addition, the researchers found that in those patients with more than 80% CD33-positive blasts, use of gemtuzumab ozogamicin significantly improved overall survival compared with best supportive care (HR, 0.49; 95% CI, 0.32–0.76). This survival benefit was less pronounced in those patients with lower CD33 expression.

“As used in this trial, gemtuzumab ozogamicin produced an overall complete remission (CR) rate of 27% (CR, 15.3%; CRi [CR with incomplete recovery of peripheral blood counts], 11.7%), with an additional 29.7% of patients achieving partial remission (5.4%), or stable disease lasting for more than 30 days (24.3%), resulting in an overall clinical benefit rate of 56.7%,” the researchers wrote. “This encouraging clinical activity translated into a median overall survival and disease-free survival of 8.2 and 5.3 months, respectively, for complete responders, and a median overall survival of 5.8 months for patients achieving lesser responses.”