Addition of Gemtuzumab Ozogamycin to Chemotherapy Improves Event-Free Survival but Not Overall Survival of AML Patients with Intermediate Cytogenetics Not Eligible for Allogeneic Transplantation. Results of the GOELAMS AML 2006 IR Study

Abstract Abstract 79 The prognosis of acute myeloblastic leukemia (AML) with intermediate-risk cytogenetics is refined further by testing the mutational status of NPM1, FLT3 and CEBPa genes. Patients with a NPM1mut3wt and CEBPa double mutation are now classified in a separate favorable group of the new ELN classification. Conversely, all other molecular profiles including these 3 genes, considered as carrying a worse prognosis, are included in ELN intermediate groups 1 and 2. Nevetheless the therapy of AML has remained unchanged since many years and needs improvement even in this subset of patients. The GOELAMS has tested the association of gemtuzumab ozozgamycin (GO), a monoclonal anti-CD33 antibody conjugated with chalicheamycin to standard chemotherapy in a phase III prospective randomized trial focusing on such patients with intermediate cytogenetics. Methods: Between 2007 and 2010, 254 patients aged between 18 to 60 years with de novo AML and intermediate karyotype have been included. The molecular status for NPM1, FLT3 and CEBPa mutations was determined at diagnosis. After 1/1 randomization, GO 6m/m2 was added to standard 3+7 induction and to a first MidAc intensive consolidation course (Mitoxantrone and intermediate doses of cytarabine). Patients in the ELN favorable molecular group received a second MidAc course followed by an autologous bone marrow transplant (BMT). Patients in the ELN intermediate 1 or 2 groups were considered for geno or phenoidentical allogeneic transplant. Patients 50 years of age or lower, received either standard allo-BMT preceded by a single course of chemotherapy or a reduced intensity chemotherapy (RIC) regimen after the two courses of intensive consolidation. In this sub-group, patients with no donor received autologous BMT after the two randomized courses of consolidation. Results: Two hundred and thirty-eight patients were analyzed with a median follow-up of 20 months. Their median age was 50 years old (18–60). There was no significant difference between the two arms according to age, WBC, % of circulating and % of marrow blasts, FAB subtypes, cytogenetics (normal vs abnormal) and molecular subgroups (favorable versus intermediate 1 and 2 ELN groups). In the GO group, the complete remission (CR) rate was 91. 6% versus 86. 5% (P=NS), early death (ED) was 10% versus 4. 5% (P=NS). Major toxicity was observed in the GO arm during induction phase with 4 cases of veno-occlusive liver disease (VOD) and overall more toxic grade III/IV hepatic toxicities (23% versus 13%, p=0. 031). No significant difference was observed between the two arms for grade III/IV hematological toxicity. No difference was observed either at 3 years for event free survival (EFS) at 51% in the GO arm and 33% in the other arm, nor for overall survival (OS) at respectively 53% and 46%. In the subset of patients who could not receive an allogeneic transplant, EFS was significantly higher in the GO group (53. 7% vs 27%, p=0. 0308) while there was no difference for OS. This better outcome was mostly observed in the group of patients classified ELN intermediate 1 or 2 (p=0. 0126). Conclusion: In the subset of patients with intermediate cytogenetics AML, the adjunction of GO to standard chemotherapy failed to improved OS, yet a better EFS was observed with the addition of GO for patients who could not receive an allogeneic SCT. More detailed results will be presented. Disclosures: No relevant conflicts of interest to declare.