Updated results ECOG-ACRIN E2906: decitabine maintenance after alloSCT

Two presentations by Dr Xiaowen Tang (Soochow University, China) and Dr James Foran (Mayo Clinic, Jacksonville, USA) suggested that decitabine maintenance therapy is an effective and safe treatment option to prevent relapse after transplantation for high-risk acute myeloid leukaemia (AML) patients [1,2].

Relapse is the most common cause of treatment failure following intensive induction and consolidation therapy in older adults with AML. The prospective, randomised, multicentre, phase 2 ECOG-ACRIN E2906 trial investigated patient outcomes after decitabine maintenance therapy compared with observation in intensively-treated older patients (≥60 years) with AML. Feasibility of decitabine maintenance was previously confirmed in a large phase 2 study [3].

The primary clinical results from the E2906 trial (n=727) demonstrated inferior overall survival of the single-agent clofarabine in comparison with standard daunorubicin and cytarabine (7+3) induction and consolidation therapy. The target accrual of the maintenance portion of the trial (step 3) was n=172, but the accrual was suspended after the recruitment of 120 patients in February 2015 by the data monitoring committee due to superior overall survival observed with standard chemotherapy versus clofarabine.

All patients were in complete remission after consolidation therapy and were randomised to either decitabine 20 mg/m2 days 1-3, every 4 weeks for 1 year (n=59) or an observation arm (n=69). The median age was 69 years (range 60-85), 74% of patients had intermediate-risk cytogenetics, and 96% had an ECOG performance status of 0-1. With a median follow-up of 49.8 months, the disease-free survival was better in the decitabine arm (15.3 months) than the observation arm (8.2 months; HR 0.77; 95% CI 0.50-1.19; P=0.12). Furthermore, the overall survival was superior in the decitabine arm (25.8 months) compared with the observation arm (19.5 months) (HR 0.69; 95% CI 0.43-1.09; P=0.06).

FLT3-ITD status was available for 96 participants, of which 84 were FLT3-ITD-negative (46 participants in the observation arm, and 38 in the decitabine arm). Importantly, the researchers observed a significant association of decitabine maintenance with superior overall survival in the large FLT3-ITD-negative subgroup; the median overall survival of decitabine was 38.3 months versus 25.2 months in the observation arm (P=0.039).

Decitabine had few safety signals and was generally well tolerated, with the exception of 9% grade 3 febrile neutropenia events, with reversible grade 4 cytopenias and no grade 5 events. In conclusion, decitabine maintenance for 1 year was associated with improved overall survival and a trend for a longer disease-free survival. The studies also demonstrated a significant impact on survival for the FLT3-ITD-negative population.

1. Tang X, et al. Abstract 3306, ASH 2019, 7-10 December, Orlando, USA.
2. Foran JM, et al. Abstract 115, ASH 2019, 7-10 December, Orlando, USA.
3. Lübbert M, et al. Haematologica. 2012 Mar;97(3):393-401.

Posted on 5 March 20205 August 2021