A retrospective study evaluating treatment patterns and survival outcomes in elderly patients with acute myeloid leukemia treated in the United States with either 7+3 or a hypomethylating agent

Bell, Jill A.; Galaznik, Aaron; Farrelly, Eileen; Blazer, Marlo; Murty, Sharanya; Ogbonnaya, Augustina; Eaddy, Michael; Fram, Robert J.; Faller, Douglas V.; Kota, Vamsi

doi:10.1016/j.leukres.2019.01.008

Cited by 15 publications

(21 citation statements)

References 12 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Zeidan¹,

Wang²,

Wang³

et al. 2020

Blood Advances

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The hypomethylating agents (HMAs) azacitidine and decitabine have been the de facto standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive therapy. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 2263 older adults (age ≥66 years) diagnosed with AML during 2005-2015 who received a first-line HMA; 1154 (51%) received azacitidine, and 1109 (49%) received decitabine. Median survival from diagnosis was 7.1 and 8.2 months (P < .01) for azacitidine- and decitabine-treated patients, respectively. Mortality risk was higher with azacitidine vs decitabine (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.01-1.21; P = .02). The findings were similar when evaluating only patients completing ≥4 cycles (42% of patients treated with either azacitidine or decitabine). These findings lost significance when evaluating those completing a standard 7-day schedule of azacitidine (34%) vs 5-day schedule for decitabine (66%) (HR, 0.95; 95% CI, 0.83-1.08; P = .43). Red blood cell (RBC) transfusion independence (TI) was achieved in one-third of patients with no difference between the 2 HMAs. In conclusion, the majority of older AML patients did not receive the minimum of 4 cycles of HMA often needed to elicit clinical benefit. We observed no clinically meaningful differences between azacitidine- and decitabine-treated patients in their achievement of RBC TI or survival.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Zeidan¹,

Wang²,

Wang³

et al. 2020

Blood Advances

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“…The median age of AML patients at diagnosis is about 70 years old . The median progression‐free survival (PFS) and overall survival (OS) of elderly AML patients (age ≥ 60) receiving standard induction treatment (7 + 3, cytarabine with an anthracycline) were 6.7 and 14.7 months, respectively . In elderly patients receiving hypomethylating agents (HMAs), the median PFS and OS were only 4.1 and 4.3 months, respectively.…”

Section: Introductionmentioning

confidence: 99%

The risk of early mortality in elderly patients with newly diagnosed acute myeloid leukemia

et al. 2020

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Background Acute myeloid leukemia (AML) is a common hematologic neoplasm with high incidence and mortality in the elderly. Our aims were to explore risk factors for early mortality in elderly AML patients and develop a new prognostic score. Methods We enrolled newly diagnosed AML patients age 60 and above at Taipei Veterans General Hospital between July 2008 and May 2017. The primary endpoint was early mortality, defined as death within two months after AML diagnosis. A multivariate Cox proportional hazards model was used to build a risk‐scoring system incorporating significant risk factors for AML. Results The final cohort included 277 elderly AML patients. The median age was 74 (range 60‐96), and 61.7% were male. The two‐month mortality rate was 29.9%. Age ≥ 80 (adjusted HR 1.88), myocardial infarction (adjusted HR 1.87), ECOG ≥ 2 (adjusted HR 2.10), complex karyotype (adjusted HR 3.21), bone marrow blasts ≥ 70% (adjusted HR 1.88), WBC ≥ 100 × 109/L (adjusted HR 3.31), and estimated glomerular filtration rate (eGFR) < 45 (adjusted HR 2.60) were identified as independent predictors for early mortality in the multivariate analysis. A simplified score incorporating the seven factors was developed with good predictive ability measured by Harrell's C statistic [0.72 (95% CI 0.66‐0.78)]. Conclusions We identified seven potential risk factors for early mortality and built up a new prognostic score for elderly AML patients. The new score may help clinicians stratify patients and initiate appropriate management. Further validation of our findings on other cohorts is warranted.

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“…Moreover, several studies suggest that not all older patients or those with comorbidities fare better with less-intensive treatments. In an analysis of data from U.S. electronic medical records for patients aged ≥60 years with newly diagnosed AML, for the whole patient cohort, OS was significantly longer following 7 + 3 induction than with an HMA [50]. Notably, even in patients with a Charlson Comorbidity Index score ≥4 (albeit only a small number of patients received either treatment), a similar benefit of 7 + 3 versus HMAs was observed (median OS: 6.7 vs 4.1 months; 1-year OS: 36.9% vs 15.9%; 2-year OS: 28.7% vs 5.3%) [50].…”

Section: Intensive Induction Chemotherapy In Older Patients and Patiementioning

confidence: 99%

The important role of intensive induction chemotherapy in the treatment of acute myeloid leukemia

Lin

Pagano

2021

Expert Review of Hematology

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Introduction: Intensive induction chemotherapy followed by post-remission consolidation and/or allogeneic hematopoietic transplantation has been a standard-of-care therapy for acute myeloid leukemia (AML) for decades. In recent years, a plethora of new agents have been approved for AML treatment, dramatically changing the AML treatment landscape.Areas covered: This review provides an overview of the current role of intensive chemotherapy in the changing AML treatment landscape. PubMed-indexed publications (through 2020) and abstracts presented at major national and international conferences were reviewed for inclusion. Expert opinion: While intensive chemotherapy is standard-of-care therapy for younger patients with AML, older patients were historically viewed as universally ineligible for intensive chemotherapy; however, several studies suggest many older patients benefit from intensive chemotherapy with a curative intent, and a more holistic approach to determining eligibility for intensive treatment is recommended. Intensive strategies have also been expanded to include novel chemotherapy designs and chemotherapy in combination with targeted agents for patients with certain disease characteristics, which may permit more personalized treatment decisions. Intensive chemotherapy continues to play a pivotal role for the management of many AML patients and can offer the best chance of long-term remission, especially when followed by transplantation.

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A retrospective study evaluating treatment patterns and survival outcomes in elderly patients with acute myeloid leukemia treated in the United States with either 7+3 or a hypomethylating agent

Cited by 15 publications

References 12 publications

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

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

The risk of early mortality in elderly patients with newly diagnosed acute myeloid leukemia

The important role of intensive induction chemotherapy in the treatment of acute myeloid leukemia

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