Gemtuzumab ozogamicin boosts overall survival in older AML patients

Older patients with newly diagnosed acute myeloid leukemia who were unsuitable for intensive chemotherapy had significantly longer overall survival with gemtuzumab ozogamicin, compared with best supportive care, according to phase III trial results published Jan. 25.

The phase III EORTC-GIMEMA AML-19 trial randomly assigned 118 patients to receive gemtuzumab ozogamicin and 119 to receive best supportive care, including hydroxyurea. The median age was 77 years. In total, 104 of 118 patients in the gemtuzumab ozogamicin arm received the full induction course, and the median number of gemtuzumab ozogamicin infusions was three (range: 1 to 10).

Median overall survival (OS) for patients who received gemtuzumab ozogamicin was 4.9 months, compared with 3.6 months for those who received best supportive care, including hydroxyurea (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90; P = .005).

One-year survival rates were 24.3% (95% CI, 16.9 to 32.4) for gemtuzumab ozogamicin and 9.7% (5.1 to 15.9) for best supportive care (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.0060).

The low intensity gemtuzumab ozogamicin regimen was generally well tolerated, with comparable toxicity between arms. Pancytopenia was observed in nearly all patients during gemtuzumab ozogamicin induction, however.

“Of importance, liver toxicity, a hallmark of [gemtuzumab ozogamicin] safety profile, was not increased in [gemtuzumab ozogamicin] recipients. Furthermore, it appeared to be less frequent and severe than previously reported by our group in a first-line trial, in which a more intensive [gemtuzumab ozogamicin] regimen was used in elderly patients with AML unfit for intensive chemotherapy,” wrote Dr. Sergio Amadori of the Tor Vergata University, Rome, and his colleagues.

Gemtuzumab ozogamicin therapy resulted in an overall complete response (CR) rate of 27% (15.3% CR and 11.7% CRi [incomplete recovery of peripheral blood counts]). The overall clinical benefit rate (CR + CRi+ partial response + stable disease for 30 days) was 56.7%.

Gemtuzumab ozogamicin combines a human monoclonal antibody specific for CD33 on myeloid cells with the DNA intercalator calicheamicin.

Patient characteristics that influenced gemtuzumab ozogamicin treatment effect were CD33 expression status, sex, and cytogenic profile. In patients with more than 80% CD33-positive blasts, gemtuzumab ozogamicin resulted in greater improvements over best supportive care (HR, 0.49; 95% CI, 0.32 to 0.76).

In women, OS was significantly improved (HR, 0.53; 95% CI, 0.35 to 0.79), whereas in men the hazard ratio was near 1. Patients with favorable/intermediate cytogenetic risk profiles had significant gemtuzumab ozogamicin benefit (HR, 0.52; 95% CI, 0.34 to 0.77), and those with adverse risk profiles had no treatment difference between arms.

The research was supported by Wyeth (Pfizer) and by the European Organisation for Research and Treatment of Cancer . Dr. Amadori reported having no disclosures. Several of his coauthors reported ties to industry.

Older patients with newly diagnosed acute myeloid leukemia who were unsuitable for intensive chemotherapy had significantly longer overall survival with gemtuzumab ozogamicin, compared with best supportive care, according to phase III trial results published Jan. 25.

The phase III EORTC-GIMEMA AML-19 trial randomly assigned 118 patients to receive gemtuzumab ozogamicin and 119 to receive best supportive care, including hydroxyurea. The median age was 77 years. In total, 104 of 118 patients in the gemtuzumab ozogamicin arm received the full induction course, and the median number of gemtuzumab ozogamicin infusions was three (range: 1 to 10).

Median overall survival (OS) for patients who received gemtuzumab ozogamicin was 4.9 months, compared with 3.6 months for those who received best supportive care, including hydroxyurea (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90; P = .005).

One-year survival rates were 24.3% (95% CI, 16.9 to 32.4) for gemtuzumab ozogamicin and 9.7% (5.1 to 15.9) for best supportive care (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.0060).

The low intensity gemtuzumab ozogamicin regimen was generally well tolerated, with comparable toxicity between arms. Pancytopenia was observed in nearly all patients during gemtuzumab ozogamicin induction, however.

“Of importance, liver toxicity, a hallmark of [gemtuzumab ozogamicin] safety profile, was not increased in [gemtuzumab ozogamicin] recipients. Furthermore, it appeared to be less frequent and severe than previously reported by our group in a first-line trial, in which a more intensive [gemtuzumab ozogamicin] regimen was used in elderly patients with AML unfit for intensive chemotherapy,” wrote Dr. Sergio Amadori of the Tor Vergata University, Rome, and his colleagues.

Gemtuzumab ozogamicin therapy resulted in an overall complete response (CR) rate of 27% (15.3% CR and 11.7% CRi [incomplete recovery of peripheral blood counts]). The overall clinical benefit rate (CR + CRi+ partial response + stable disease for 30 days) was 56.7%.

Gemtuzumab ozogamicin combines a human monoclonal antibody specific for CD33 on myeloid cells with the DNA intercalator calicheamicin.

Patient characteristics that influenced gemtuzumab ozogamicin treatment effect were CD33 expression status, sex, and cytogenic profile. In patients with more than 80% CD33-positive blasts, gemtuzumab ozogamicin resulted in greater improvements over best supportive care (HR, 0.49; 95% CI, 0.32 to 0.76).

In women, OS was significantly improved (HR, 0.53; 95% CI, 0.35 to 0.79), whereas in men the hazard ratio was near 1. Patients with favorable/intermediate cytogenetic risk profiles had significant gemtuzumab ozogamicin benefit (HR, 0.52; 95% CI, 0.34 to 0.77), and those with adverse risk profiles had no treatment difference between arms.

The research was supported by Wyeth (Pfizer) and by the European Organisation for Research and Treatment of Cancer . Dr. Amadori reported having no disclosures. Several of his coauthors reported ties to industry.

Older patients with newly diagnosed acute myeloid leukemia who were unsuitable for intensive chemotherapy had significantly longer overall survival with gemtuzumab ozogamicin, compared with best supportive care, according to phase III trial results published Jan. 25.

The phase III EORTC-GIMEMA AML-19 trial randomly assigned 118 patients to receive gemtuzumab ozogamicin and 119 to receive best supportive care, including hydroxyurea. The median age was 77 years. In total, 104 of 118 patients in the gemtuzumab ozogamicin arm received the full induction course, and the median number of gemtuzumab ozogamicin infusions was three (range: 1 to 10).

Median overall survival (OS) for patients who received gemtuzumab ozogamicin was 4.9 months, compared with 3.6 months for those who received best supportive care, including hydroxyurea (hazard ratio, 0.69; 95% confidence interval, 0.53-0.90; P = .005).

One-year survival rates were 24.3% (95% CI, 16.9 to 32.4) for gemtuzumab ozogamicin and 9.7% (5.1 to 15.9) for best supportive care (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.0060).

The low intensity gemtuzumab ozogamicin regimen was generally well tolerated, with comparable toxicity between arms. Pancytopenia was observed in nearly all patients during gemtuzumab ozogamicin induction, however.

“Of importance, liver toxicity, a hallmark of [gemtuzumab ozogamicin] safety profile, was not increased in [gemtuzumab ozogamicin] recipients. Furthermore, it appeared to be less frequent and severe than previously reported by our group in a first-line trial, in which a more intensive [gemtuzumab ozogamicin] regimen was used in elderly patients with AML unfit for intensive chemotherapy,” wrote Dr. Sergio Amadori of the Tor Vergata University, Rome, and his colleagues.

Gemtuzumab ozogamicin therapy resulted in an overall complete response (CR) rate of 27% (15.3% CR and 11.7% CRi [incomplete recovery of peripheral blood counts]). The overall clinical benefit rate (CR + CRi+ partial response + stable disease for 30 days) was 56.7%.

Gemtuzumab ozogamicin combines a human monoclonal antibody specific for CD33 on myeloid cells with the DNA intercalator calicheamicin.

Patient characteristics that influenced gemtuzumab ozogamicin treatment effect were CD33 expression status, sex, and cytogenic profile. In patients with more than 80% CD33-positive blasts, gemtuzumab ozogamicin resulted in greater improvements over best supportive care (HR, 0.49; 95% CI, 0.32 to 0.76).

In women, OS was significantly improved (HR, 0.53; 95% CI, 0.35 to 0.79), whereas in men the hazard ratio was near 1. Patients with favorable/intermediate cytogenetic risk profiles had significant gemtuzumab ozogamicin benefit (HR, 0.52; 95% CI, 0.34 to 0.77), and those with adverse risk profiles had no treatment difference between arms.

The research was supported by Wyeth (Pfizer) and by the European Organisation for Research and Treatment of Cancer . Dr. Amadori reported having no disclosures. Several of his coauthors reported ties to industry.