Efficacy and safety of decitabine monotherapy vs intensive chemotherapy in older patients with AML

Survival outcomes in older patients with acute myeloid leukemia (AML) have significantly improved with reduced-intensity conditioning followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, it is uncertain whether cytarabine-based standard remission induction chemotherapy (3 + 7) is optimal before allo-HSCT. Lübbert et al.¹ recently published the results of a phase III trial of decitabine vs intensive chemotherapy followed by allo-HSCT in older patients with AML (NCT02172872) in Lancet Hematology. Here, we are pleased to summarize the key findings.

Study design and patient population

This open-label randomized controlled trial included 606 patients aged ≥60 years with newly diagnosed AML who were eligible for intensive chemotherapy. The study design and patient characteristics have been previously reported by the AML Hub. The median age was 68 years (range, 60–81 years), and 92% of patients had an Eastern Cooperative Oncology Group performance status of 0 to 1.

• Primary endpoint: Overall survival (OS), defined as time from randomization to death from any cause.
• Secondary endpoints: Rate of complete remission (CR) or complete remission with incomplete hematologic recovery (CRi), progression-free survival, and disease-free survival.

Key findings

• In total, 302 patients received decitabine and 298 received 3 + 7
• Rates of on-protocol allo-HSCT were similar between the decitabine and 3 + 7 groups (40% vs 39%)
• At a median follow-up of 4 years (interquartile range, 2.9–4.8 years), the median OS was 15 months (95% confidence interval [CI], 13–18) and 18 months (95% CI, 14–22) in the decitabine and 3 + 7 group, respectively.
• Figure 1 shows 4-year OS, progression-free survival, and disease-free survival rates.

Figure 1. 4-year survival outcomes* 

DFS, disease-free survival; OS, overall survival; PFS, progression-free survival.

*Adapted from Lübbert, et al.¹

• In the decitabine and 3 + 7 group, CR or CRi was achieved by 48% (95% CI, 42–54) and 61% (95% CI, 56–67) of patients, respectively.  
  • Following post-protocol treatment, CR or CRi was achieved by 60% and 67% of patients in the decitabine and 3 + 7 groups, respectively (adjusted odds ratio, 0.75; 95% CI, 0.54–1.05).
• Subgroup analysis by age and European LeukemiaNet risk group showed that CR or CRi was higher in the 3 + 7 group compared with the decitabine group, except for patients classified as adverse-risk (Figure 2).
  • Patients with mutated NPM1 had a hazard ratio of 2 (95% CI, 0.96–4.17) vs 1.02 (95% CI, 0.77–1.34) in patients with wildtype NPM1 (p = 0.026).

Figure 2. Subgroup analysis: response rates by age and ELN risk group* 

ELN, European LeukemiaNet.

*Adapted from Lübbert, et al.¹

• There were 218 deaths in the decitabine group and 205 deaths in the 3 + 7 group (hazard ratio, 1.04; 95% CI, 0.86–1.26; p = 0.68).
  • Treatment-related deaths occurred in 12% and 14% of patients in the decitabine and 3 + 7 groups, respectively.
• Grade 3–5 adverse events were lower in the decitabine vs 3 + 7 group (Figure 3).

Figure 3. Adverse events*

AEs, adverse events.

*Adapted from Lübbert, et al.¹