Suboptimal Use of Initial Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia


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Vijaya Raj Bhatt, MD

Vijaya Raj Bhatt, MD

IN A STUDY of National Cancer Database data reported in Blood Advances, Vijaya Raj Bhatt, MD, of the University of Nebraska Medical Center, and colleagues found that 25% of patients with newly diagnosed acute myeloid leukemia (AML) did not receive initial chemotherapy, despite evidence that chemotherapy is associated with a survival benefit and improvement in symptoms in this setting.1 Prior studies have found lower use of chemotherapy with increasing age and comorbidities. The current study confirmed these findings and also noted that the use of chemotherapy was affected by socioeconomic and health-system factors.

Study Details

THE STUDY included 61,775 adults with AML diagnosed between 2003 and 2011 from the National Cancer Database. Multivariable logistic regression modeling was used to determine the association between the receipt of chemotherapy and variables including disease characteristic and clinical, socioeconomic, and health-system factors. Nearly all patients (97.7%) received care in urban facilities.

Frequency of Chemotherapy Use

AMONG ALL patients, 15,608 (25.3%) did not receive chemotherapy and 46,167 (74.7%) received chemotherapy. Chemotherapy was initiated within a median of 4 days after diagnosis (interquartile range = 2–10 days; range = 0–1,098 days). Among patients receiving chemotherapy, treatment was multiagent in 74.9%, single agent in 21.8%, and unspecified in 3.3%. Among patients not receiving chemotherapy, the reasons cited for not receiving treatment were unspecified in 72.8% of cases, contraindications including comorbidities or advanced age in 11.4%, patient or family refusal in 11.3%, death before therapy in 3.8%, and recommended but not given for unspecified reasons in 0.7%. For patients given vs not given chemotherapy, 1-month mortality was 11.8% vs 53.6%, and 5-year overall survival was 25.8% vs 2.6%.

On univariate analysis, factors significantly associated with a lower likelihood of receiving chemotherapy were increasing age (particularly age ≥ 60 years); higher Charlson comorbidity score; therapy-related AML or intermediate-/high-risk AML vs core binding factor AML and acute promyelocytic leukemia; female sex; white race; lower educational status; lower income; uninsured status; and receipt of care in nonacademic centers and low-volume hospitals. Chemotherapy was more likely to be received by patients traveling longer distances for care.

“Chemotherapy use should be maximized [in AML], especially as we enter the era of more effective and better tolerated novel and molecularly targeted therapies.”
— Vijaya Raj Bhatt, MD

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Factors Associated With Lower Likelihood of Treatment

ON MULTIVARIATE analysis, 2-way interactions for age by insurance status (P < .001) and age by Charlson comorbidity score (P < .0001) were statistically significant. The likelihood of receiving chemotherapy was reduced with increasing age, higher Charlson comorbidity score, and uninsured or Medicare insurance status (all P < .0001).

The likelihood of chemotherapy use differed significantly according to AML subtype (overall P < .0001). For example, chemotherapy use was less likely for therapy-related AML (odds ratio = 0.62, 95% confidence interval [CI] = 0.51–0.74, vs other intermediate-/high-risk disease; odds ratio = 0.54 , 95% CI = 0.44–0.67, vs acute promyelocytic leukemia) and for intermediate-/high-risk AML (odds ratio = 0.88, 95% CI = 0.80–0.97, vs acute promyelocytic leukemia); chemotherapy use was more likely in patients with core binding factor AML vs therapy-related AML (odds ratio = 2.32, 95% CI = 1.82–2.96), other intermediate-/high-risk disease (odds ratio = 1.43, 95% CI = 1.22–1.68), and acute promyelocytic leukemia (odds ratio = 1.26, 95% CI = 1.05–1.52).

Lower hospital volume was associated with a lower likelihood of chemotherapy receipt (odds ratio = 1.02, P < .0001, for hospital volume as a continuous variable). Female sex (odds ratio = 1.07, P = .001, for male vs female), African American race (odds ratio = 0.84, 95% CI = 0.73–0.96, vs other; odds ratio = 0.85, 95% CI = 0.78–0.93, vs white; overall P = .0009), and lower income status (eg, odds ratio = 0.80, 95% CI = 0.74–0.87, for annual household income of $30,000 vs ≥ $46,000; overall P < .0001) also were independently associated with a reduced likelihood of receiving chemotherapy.

USE OF CHEMOTHERAPY FOR AML

  • Chemotherapy was not used in 25% of patients with newly diagnosed disease.
  • Factors associated with a lower likelihood of use of chemotherapy included racial, insurance, and income status as well as treatment facility type.

Chemotherapy use was significantly more likely for patients treated in academic vs nonacademic centers (odds ratio = 1.51, P < .0001) and for patients who traveled longer distances to receive treatment (eg, odds ratio = 1.26, 95% CI = 1.18–1.34, for 12–34.7 vs 0–4.9 miles; odds ratio = 1.41, 95% CI = 1.31–1.52, for ≥ 34.8 vs 0–4.9 miles; overall P < .0001).

The investigators concluded: “[A] quarter of patients with newly diagnosed AML do not receive chemotherapy in the United States. Whereas the lower receipt of chemotherapy is expected among older patients, patients with significant comorbidities, and those with high-risk AML, racial, insurance and income status, and facility type also influenced the likelihood of receiving chemotherapy. These findings raise a possibility of leukemia care disparity based on socioeconomic and health system factors. Early diagnosis of AML, multidisciplinary management of leukemia emergencies and comorbidities, and strengthening the partnership between academic leukemia experts and community oncologists are some of the potential ways to increase the use of chemotherapy…. Chemotherapy use should be maximized, especially as we enter the era of more effective and better tolerated novel and molecularly targeted therapies.” ■

DISCLOSURE: Dr. Bhatt has served as a consultant for Pfizer and CSL Behring. For full disclosures of the other study authors, visit bloodadvances.org.

REFERENCE

1. Bhatt VR, Shostrom V, Gundabolu K, et al: Utilization of initial chemotherapy for newly diagnosed acute myeloid leukemia in the United States. Blood Adv 2:1277-1282, 2018.


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