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. 2018 Dec:75:29-35.
doi: 10.1016/j.leukres.2018.10.011. Epub 2018 Oct 25.

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

Pankit Vachhani  1 , Raed Al Yacoub  2 , Austin Miller  3 , Fan Zhang  3 , Tara L Cronin  4 , Evelena P Ontiveros  4 , James E Thompson  4 , Elizabeth A Griffiths  4 , Eunice S Wang  4
Affiliations

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

Pankit Vachhani et al. Leuk Res. 2018 Dec.

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 high-risk 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.

Keywords: Azacitidine; Decitabine; Epigenetic therapy; High-risk; Hypomethylating agents; Intensive chemotherapy; Secondary AML.

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Conflict of interest statement

Conflict of interest disclosure: The authors have no relevant conflicts of interest to report.

Figures

Figure 1:
Figure 1:
Kaplan-Meier curves for OS (A) and DOR (B). IC led to an improved OS but results did not reach statistical significance (p=0.07). DOR, similarly, was not statistically different for patients in the two therapy cohorts. OS: overall survival; DOR: duration of response; IC: intensive chemotherapy.
Figure 1:
Figure 1:
Kaplan-Meier curves for OS (A) and DOR (B). IC led to an improved OS but results did not reach statistical significance (p=0.07). DOR, similarly, was not statistically different for patients in the two therapy cohorts. OS: overall survival; DOR: duration of response; IC: intensive chemotherapy.
Figure 2:
Figure 2:
Kaplan-Meier curves for OS based on therapies and comorbidity burden using CCI (A) and TRM (B) scoring models. Patients with less comorbidity burden had better OS. OS: Overall survival; CCI: Charlson Comorbidity Index; TRM: therapy related mortality
Figure 2:
Figure 2:
Kaplan-Meier curves for OS based on therapies and comorbidity burden using CCI (A) and TRM (B) scoring models. Patients with less comorbidity burden had better OS. OS: Overall survival; CCI: Charlson Comorbidity Index; TRM: therapy related mortality
See this image and copyright information in PMC

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