Question 13 - Reading Comprehension Practice Test for the DAT

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by aggressive clonal proliferation of myeloid blasts in the bone marrow and blood, with a poor prognosis. AML is the predominant form of acute leukemia diagnosed in adults, and its incidence and mortality are even higher in older populations. According to the Surveillance, Epidemiology, and End Results (SEER) program, leukemia is projected to account for 3.0% of all new cancer diagnoses, and 3.9% of all cancer-related deaths in 2023.

AML is characterized by significant variations in treatment approaches, disease management strategies, and prognoses based on age. Different populations exhibit heterogeneity in treatment methods, rates, and outcomes. Long-term follow-up registry data of leukemia patients in Osaka, Japan, showed an improvement in the 5-year survival rate of AML in children and adolescents from 7.0% to 77.0% and from 5.2% to 66.5% respectively from 1975–2011. However, older AML patients who are 65 years or older showed a poor 5-year survival rate of 12.5% during 2009–2013 with a treatment rate of approximately 50%, based on the SEER database. A nationwide population study in the Netherlands reported a similar survival rate of 14% between 2007–2012. According to more recent data from the SEER-Medicare database from 2008–2015, the treatment rate, encompassing both AML treatment and supportive care, rose to 69.04%, while the rate of AML treatment alone stood at 27.17%.

These results indicate an unmet need for AML treatment in older individuals. Since the late 2000s, hypomethylating agent (HMA) therapies such as azacytidine and decitabine for older patients with newly diagnosed AML, and those who are unable to undergo intensive chemotherapy have been implemented. This has raised expectations of enhanced treatment rates and outcomes for those aged 65 years or older, as demonstrated in clinical trials. However, the treatment effects of monotherapy are modest at best and are unlikely to have significantly altered survival outcomes. Therefore, combination regimens such as venetoclax plus HMA were introduced in 2019. The standard of care for newly diagnosed AML still remains with HAM therapies in South Korea until early 2023, and there are concerns about the limited improvement of AML survival in the elderly.

Our findings confirm and uniquely present the hazard ratios (HRs) of important factors of de novo AML mortality. These results align with prior studies highlighting increased HRs for populations aged 60 or older. However, only some of these past studies have provided the overall survival hazard ratio (OS HR) of the older population compared with that of the younger population. AML is well known for its poor prognosis and limited improvement in treatment outcomes in older patients. The rates of our patients with treated de novo AML are similar to those of a previous study, with a 71% treatment rate. However, aging and intensive treatment rates are interrelated factors and require careful attention with the complex source of unmet treatment needs in this aging era. Intensive therapy, including chemotherapy and HSCT, can be influenced by factors related to patients, disease-specific factors, and socioeconomic characteristics. Importantly, patients with de novo AML are more likely to receive intensive treatment than secondary AML patients, and the treatment rate for t-AML is only approximately 66%, even though most t-AML patients are younger than 65 years. The untreated cohort of newly diagnosed patients with AML, which tends to increase with age, comorbidities, and socio-economic challenges, warrants greater clinical attention. Therefore, more attention should be paid to care and treatment strategies, especially in older patients, to improve survival.

The period of diagnosis did not significantly influence OS across age groups. However, our adjusted Cox analysis showed an approximately 10% improvement in OS among the most recently diagnosed patients with de novo AML compared to that from earlier periods. This improvement may be associated with Korea’s recent expansion of reimbursed treatments for older patients with de novo AML, including the introduction of two hypomethylating agents: decitabine in December 2013 and azacytidine in September 2017. These survival improvements are also attributed to advanced supportive care such as hematopoietic cell stimulating agents, antimicrobials, and improved transfusion care. The HIRA database, which includes all Korean patients with AML with a history of health insurance claims, is a powerful population-based dataset; however, it has several limitations. First, the lack of molecular or cytogenetic information cannot fully address prognostic factors that may affect survival. Second, the nature of claims data could induce under- or over-estimation of comorbidities estimated by the CCI scores based on the diagnosis in the claims database. The ICD-10 code-based claims database diagnoses could be underestimated or overestimated in some cases. However, this would not significantly deteriorate the accuracy of AML diagnosis because research has confirmed that the accuracy of cancer diagnoses is higher than 92% using the NHIS claims database. Another database-related limitation of our study is the accuracy of the mortality data in the claims database. Although claims data are known to have limitations in capturing mortality information because they only include hospital deaths, the death indicator of the NHIS has a true positive rate of 97% for high-risk cancers. This study acknowledges a limitation regarding the assessment of the impact of the venetoclax plus HMA regimen on the elderly population. Although the combination of venetoclax and HMA represents a significant advancement in AML treatment since its introduction in 2019, this regimen has only been covered by insurance starting from February 2023 in South Korea. Consequently, the data reflecting the full potential benefits of this treatment are limited within the timeframe of our study. Future research, encompassing a longer observation period, is required to comprehensively evaluate the effects of venetoclax and HMA on the management and outcomes of AML in the elderly population.

In summary, our study revealed an increasing age-specific incidence of de novo AML among the population aged 60 years or older and yet a decreasing trend in the annual ASIR derived from a nationally representative population database. The unadjusted survival rate worsened among patients older than 65 years; however, after adjustment in the Cox analysis, we observed an improvement in survival rates over the study period for the overall population. Our findings suggest that there is a pronounced need for further well-designed studies to validate the impact of expanded treatment options for older patients with AML and to explore strategies for improving treatment outcomes in this population.

Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84–0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.