Autologous transplantation gives encouraging results for young adults with favorable-risk acute myeloid leukemia, but is not improved with gemtuzumab ozogamicin

Abstract

We report the results of a prospective, randomized phase 3 trial evaluating the use of gemtuzumab ozogamicin (GO) in an intensive consolidation approach in 657 patients 17-60 years of age. Patients in first complete remission (CR1) after cytarabine and standard- or high-dose daunorubicin induction received 2 cycles of consolidation with high-dose cytarabine followed by peripheral blood progenitor cell collection. The 352 patients who entered consolidation were randomized to receive GO (n = 132) or not (n = 138) and then proceeded to autologous hematopoietic cell transplantation (HCT). GO was given to 67 patients. Median follow-up was 50.9 months. Results of the intention-to-treat analysis demonstrated a 4-year disease-free survival (DFS) of 33.6% versus 35.9% (P = .54) and an overall survival (OS) of 41.3% versus 41.9% (P = .52) for those randomized to receive GO versus no GO, respectively. Patients with favorable- and intermediate-risk acute myeloid leukemia (AML) treated with high-dose daunorubicin and autologous HCT had 4-year DFS rates of 60% and 40% and OS rates of 80% and 49.3%, respectively. For younger AML patients in CR1, autologous HCT should be considered in favorable- and intermediate-cytogenetic risk patients who do not have an allogeneic donor. The addition of a single dose of GO in this setting did not improve outcomes.

Trial registration: ClinicalTrials.gov NCT00049517.

Figure 1

Schema of ECOG trial E1900. Patients in remission after induction therapy were allocated based on risk factors (as defined in “Treatment”). The autologous consolidation randomization to gemtuzumab ozogamicin was closed in October 2007. Eligibility requirements for autologous HCT are given in “Treatment.” HiDAC indicates high-dose cytarabine.

Figure 2

Kaplan-Meier estimates of DFS and OS. Data from the ITT analysis are shown for DFS (A) and OS (B) of all patients treated in the autologous randomization arms of the trial. Data are from the time of randomization at the start of consolidation. The investigational arm contained the additional treatment with gemtuzumab ozogamicin. CNSR indicates censured.

Figure 3

Kaplan-Meier estimates of DFS and OS. Autologous HCT data from the subset analysis are shown for DFS (A) and OS (B) for patients who received protocol-prescribed autologous HCT. Data are from the time of transplantation. The investigational arm contained the additional treatment with GO. CNSR indicates censured.

Figure 4

Cumulative incidence of relapse and death without relapse. Data from the ITT analysis are shown for the cumulative incidence of relapse and for deaths without relapse of all patients allocated to the autologous randomization arms of the trial. Data are from the time of randomization at the start of consolidation. The investigational arm contained the additional treatment with GO.

Figure 5

Kaplan-Meier estimates of DFS and OS. Based on induction therapy, cytogenetic risk and received autologous HCT. Data from the subset analysis are shown for DFS (A) and OS (B) for patients who received protocol-prescribed autologous HCT based on the induction therapy standard (45 mg/m²) or high-dose (90 mg/m²) and on cytogenetic risk group. The analysis is regardless of the addition of GO during consolidation. Data are from the time of randomization at the start of transplantation. CNSR indicates censured.

Figure 6

Kaplan-Meier estimates of DFS and OS. Estimates are based on CD34 cell dose infused during autologous HCT. Data from the subset analysis are shown for DFS (A) and OS (B) for patients who received protocol-prescribed autologous HCT. Cell dose is per kilogram of body weight. Data are from the time of randomization at the start of transplantation. The analysis is regardless of the addition of GO during consolidation. CNSR indicates censured.