Older patients with acute myeloid leukemia who were treated with decitabine experienced comparable outcomes vs daunorubicin and cytarabine.
In addition to an improved safety profile, treatment with decitabine resulted in a similar rate of overall survival (OS) and hematopoietic stem cell transplantation (HSCT) vs a chemotherapy regimen consisting of daunorubicin and cytarabine (Vyxeos) in an older population with acute myeloid leukemia (AML).
Findings from a phase 3 study (NCT02172872) that were presented at the 2022 European Hematologic Association Congress indicated that the 4-year OS rate was 26% (95% CI, 21%-32%) in the experimental arm of patients who were 60 years or older compared with 30% (95% CI, 24%-35%) in the control arm (HR, 1.04; 95% CI, 0.86-1.26; P = .68). The rate of HSCT was 52% in both cohorts. Among those treated with decitabine, 40% underwent on-protocol HSCT and 12% underwent off-protocol HSCT vs 39% and 13% in the chemotherapy cohort, respectively.
Among those who received on-protocol HSCT, the 1-, 2-, 3-, and 4-year OS rates were 66%, 56%, 50%, and 45% in the experimental arm compared with 75%, 58%, 51%, and 47%, in the chemotherapy arm, respectively. Although a longer OS was observed in patients 70 years or older treated with decitabine (HR, 0.84; 95% CI, 0.55-1.26), those who were 60 to 64 years (HR, 1.34; 95% CI, 0.79-2.28) or who were NPM1 mutant (HR, 2.0; 95% CI, 0.96-4.17) had a worse OS following treatment with the agent.
A total of 606 patients with newly diagnosed or de novo/secondary untreated disease were included in the study. Patients were required to be at least 60 years of age and candidates for an intensive 3+7 chemotherapy regimen. Moreover, at randomization, white blood cell counts couldn't be more than 30 x 109/L. Those who enrolled were randomly assigned 1:1 to receive either the 10-day decitabine regimen (n = 303) or intensive chemotherapy (n = 303).
The trial's primary end point was OS, and key secondary end points included complete response (CR) and CR with incomplete count recovery (CRi), progression-free survival, disease-free survival, transplantation rate and outcome, and safety profile.
In terms of other study findings, the 4-year relapse/progressive disease rates were 57% and 51% in the decitabine and chemotherapy arms, respectively. Moreover, the respective treatment-related mortality rates were 21% and 25% in both respective arms.
Patients treated in the experimental arm had a lower incidence of grade 3 to 5 adverse effects (AEs) vs the chemotherapy arm, including a lower rate of blood and lymphatic disorders, infections, and gastrointestinal disorders. Notably, following HSCT, 25% of patients in the decitabine arm developed grade 5 treatment-related AEs vs 22% of those in the chemotherapy arm.
Lübbert M, Wijermans P, Kicinski M, et al. 10-day decitabine versus conventional chemotherapy (“3+7”) followed by allografting in AML patients ≥60 years: a randomized phase III study of the EORTC Leukemia Group, CELG, GIMEMA and German MDS Study Group. Presented at: EHA 2022 Hybrid Congress; June 9-12, 2022; Vienna, Austria. Abstract S125.