Patterns of Undertreatment Among Patients with Acute Myeloid Leukemia (AML) Not Receiving Standard Intensive Induction Chemotherapy

Introduction: AML, a life-threatening malignancy, is most common in older adults. Due to the advanced age and heterogeneity of the patient population, selecting appropriate therapy presents a challenge for clinicians. Studies have demonstrated that regardless of age, patients with AML benefit from receiving antileukemic therapy, including standard intensive induction and non-intensive chemotherapy, and current guidelines recommend that treatment selection be based on individual patient and disease characteristics, e.g., performance status (PS), cytogenetic risk, comorbidity burden, and age. Nevertheless, historic data suggest that a high proportion of patients with AML who are candidates for non-intensive therapy receive no leukemia treatment. This literature review aimed to assess current real-world patterns of undertreatment in AML.

Methods: A strategic literature review was conducted using the pearl growing/snowball method, wherein core publications were identified using an initial Pubmed search strategy with the MeSH heading “Acute Myeloid Leukemia” and the search terms "treatment pattern", "treatment decision", "treatment utilization”. Results were limited to English-language publications dated January 2010 to May 2020. A total of 831 initial results were retrieved. Nine core publications were used to establish keywords and for bibliographic and prospective citation searches to identify additional relevant publications.

Results: Thirty studies reported the proportion of patients with AML receiving no antileukemic therapy among a total of 65,989 patients. The majority of studies were from the US; the EU, UK, Japan, Brazil, India, Israel, and Serbia were also represented. Ten studies were single center, while the rest were multicenter or analyzed registries; the Surveillance, Epidemiology, and End Results (SEER) program database; Centers for Medicare and Medicaid Services’ claims; or commercially available claims databases.

In the US, the percentage of patients who received no antileukemic therapy ranged from 10% to 61.4%, with a pooled average of 38%. In the EU, between 24.1% and 35% of patients received only best supportive care (BSC). Most studies reported an association between increased age and decreased likelihood of receiving leukemia therapy. Patients who did not receive antileukemic therapy tended to have higher comorbidity burden and poorer Eastern Cooperative Oncology Group (ECOG) or Karnofsky PS than those who received non-intensive treatment (e.g., hypomethylating agent or reduced intensity chemotherapy regimen) or standard intensive induction chemotherapy. Sociodemographic characteristics associated with increased likelihood of not receiving antileukemic therapy included female sex, unmarried status, and Black race. Four studies described rationales for selecting BSC only. Among these, three cited poor PS and uncontrolled concomitant medical conditions such as diabetes and severe cardiovascular disease, and three included patient refusal of treatment. Patients who did not receive antileukemic treatment experienced diminished overall survival (OS). Across all studies reporting survival outcomes, median OS for patients receiving BSC only ranged from 11 days to 4.8 months versus 7 months to over 14 months for patients who received antileukemic therapy.

Conclusions: This literature review found that on average, nearly a third of patients with AML do not receive antileukemic therapy. In identified studies reporting survival outcomes, any leukemia treatment provided survival benefits compared with no anticancer treatment. Though patients who received BSC only tended to be older with more comorbidities and poorer PS, other variables may influence treatment decisions. With the availability of effective, less intensive treatments for AML, there may be a proportion of patients who could benefit from antileukemic therapy but do not receive it. Increased understanding of prognostic factors, disparities in access to healthcare, and patient preferences, as well as the development of a consensus on eligibility for active non-intensive treatment, will help maximize treatment options and ensure appropriate care of patients with AML. The information identified in this strategic literature review supports clinicians in considering antileukemic therapy for patients who otherwise may have received only BSC.