Intensive chemotherapy vs. hypomethylating agents in older adults with newly diagnosed high-risk acute myeloid leukemia: A single center experience

Abstract

Acute myeloid leukemia (AML) in older patients is often associated with biologic and clinical characteristics that predict poor outcomes to cytarabine and anthracycline based induction chemotherapy (IC). The impact of hypomethylating agents (HMA) in the treatment of these highrisk patients is unknown. Here we retrospectively examined the remission rates and survival outcomes of 201 newly diagnosed patients ≥ 60 years old with therapy-related (t-AML), secondary (s-AML), or AML with myelodysplasia-related changes (AML-MRC). Ninety-eight patients received IC, and 103 received HMA. Patients in the IC cohort were younger than those who received HMA (68 vs. 74 years; p<0.01) with lower comorbidity burden. Composite complete remission rates (CR) were 39% in IC and 27% in the HMA cohorts (p=0.10). Overall survival (OS) was not significantly different between the two cohorts (7.59 mos vs. 5.49 mos; HR 0.75 95% CI 0.55-1.02) despite the fact that more patients in the IC cohort (33% versus 5%, p<0.01) underwent allogeneic stem cell transplant. Patients with t-AML (HR 0.56; 95% CI 0.33-0.97) and complex karyotype without monosomal karyotype (CK+MK-; HR 0.37; 95% CI 0.19-0.75) had better OS following IC. Patients with CK+MK+ (HR 2.00; 95% CI 1.08-3.70) had improved OS following HMA. Our results support the use of HMA as an alternative upfront regimen in older individuals with newly diagnosed high-risk AML based on similar clinical outcomes to IC.

Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States

“…We observed that azacitidine and decitabine were used in nearly identical proportions in the study sample, consistent with recent population studies. [16][17][18] This pattern differs from the real-world treatment of patients with myelodysplastic syndrome, for whom azacitidine is used much more frequently. 31 Our study further examines dosing regimens and the association with outcomes.…”

“…11 More recent studies reported that 40% to 60% of newly diagnosed older AML patients receive an HMA. [16][17][18] Real-world evidence for the clinical benefits of HMAs in older AML patients is limited, and the 2 approved HMAs have not been directly compared in large clinical trials. This gap in evidence is increasingly problematic, as HMAs have become the backbone for combination regimens (eg, with venetoclax), with approval based on singlearm studies without an HMA monotherapy control arm.…”

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

“…There were 20 studies addressing this question, reported in 21 publications, 54,62,64,76,80,90,92,101,104,[121][122][123][124][125][126][127][128][129][130][131][132] the majority of which were observational. 54,62,76,80,90,92,101,104,[121][122][123][124][125][126][127][128][129][130][131][132] One study was an RCT 64 in which patients in the standard-of-care arm were preselected by their physicians to receive either intensive (induction) therapy, less-intensive therapy, or best supportive care, vs less-intensive therapy with azacitidine. For this study, for outcomes in which the researchers presented data comparing intensive therapy to azacitidine among patients preselected for intensive therapy, we used this as RCT data.…”

“…Very low-quality evidence suggests that patients who receive intensive antileukemic therapy may be at lower risk of death than those who receive less-intensive antileukemic therapy, over time (HR, 0.78; 95% confidence interval, 0.69-0.89). 62,80,90,101,104,121,124,125,129,132 Very low-quality evidence suggests that the risk of death may also lower at 1 year (risk ratio, 0.93; 95% confidence interval, 0.85-1.01). 54,62,76,90,92,104,121,123,[127][128][129]132 Low-quality evidence suggests the likelihood that patients who receive intensive antileukemic therapy are 6.6 times more likely to receive an allo-HSCT than those who receive less-intensive antileukemic therapy (risk ratio, 6.65; 95% confidence interval, 4.13-10.71).…”

Indirect comparison of azacitidine and decitabine for the therapy of elderly patients with acute myeloid leukemia: a systematic review and network meta-analysis

“…HMAs are still common methods for elderly AML patients who are unfit for intensive therapy or HSCT [24]. NCCN recommendations list treatment with azacitidine and decitabine for elderly patients with newly diagnosed AML as an option [13].…”