Economic Burden of Patients Treated for Higher-Risk Myelodysplastic Syndromes (HR-MDS) in Routine Clinical Care in the United States

Myelodysplastic syndromes (MDS) are a group of heterogeneous, malignant bone marrow disorders characterized by ineffective hematopoiesis leading to disease-related complications and death [1]. Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database (2007–2011) estimated the age-adjusted incidence to be 4.9 per 100,000 per year, and rates increase with increasing age, indicating that MDS is a disease of the elderly [2]. The incidence is 13.5 per 100,000 in those aged 65–69 years and 63.6 per 100,000 in those aged ≥ 85 years [2]. However, it has been documented that registries have underestimated the incidence of MDS due to underreporting and underdiagnosis; the estimated prevalence of MDS in the United States (US) is between 60,000 and 170,000 and is projected to grow [2].

The Revised International Prognostic Scoring System (IPSS-R) for MDS is used to determine the prognosis of patients diagnosed with MDS. IPSS-R classifies patients into five distinct risk categories (very low, low, intermediate, high, and very high) based on cytogenetics, bone marrow blast percentage, and depth of cytopenias at the time of diagnosis, with the median survival decreasing with increasing IPSS-R risk score [3]. Moreover, IPSS-R risk classification is used to largely guide treatment decisions; for patients with higher-risk MDS (HR-MDS, defined as an IPSS-R risk classification of intermediate risk or higher), the National Comprehensive Cancer Network (NCCN) recommends hypomethylating agents (HMAs) (e.g., azacitidine or decitabine) or a clinical trial for patients unable to undergo allogenic stem cell transplantation (alloSCT) [4]. For transplant-eligible HR-MDS patients, alloSCT alone or after either high-intensity chemotherapy (most commonly with an antimetabolite with or without an anthracycline) or chemotherapy with an HMA is recommended [4].

Healthcare utilization among patients with MDS is high. Patients often experience frequent and prolonged hospitalizations, frequent outpatient visits, and high costs [5]. The cost of treatment of MDS has been shown to be significantly higher in those patients receiving HMAs compared to patients who did not [6]. However, HMAs have demonstrated the ability to significantly reduce the transfusion burden in this patient population, which is also a substantial medical cost for patients with MDS [2, 7]. In fact, another retrospective claims analysis demonstrated that patients with MDS have a higher risk of emergency department (ED) visits and inpatient admissions during periods of follow-up when transfusions are administered versus during transfusion-free periods [8]. Both of the HMAs (i.e., azacitidine and decitabine) have been shown to be cost-effective options for the treatment of patients with HR-MDS, but azacitidine has been shown to be more cost-effective than decitabine in a recent analysis [9, 10]. This realization of cost effectiveness is likely due to both decreased transfusion dependence and fewer patients progressing to acute myeloid leukemia (AML) [10]. Overall, however, there are little data on current healthcare utilization and costs associated with treating HR-MDS in routine clinical practice. This study assessed the total healthcare costs and utilization of newly diagnosed HR-MDS patients.

This study evaluated healthcare utilization and costs among treated HR-MDS patients in routine clinical practice and revealed that the healthcare burden associated with HR-MDS is considerable, particularly in the first year following diagnosis relative to the second year, across all settings of care. While overall costs PPPM were higher in the first year after diagnosis ($17,361 PPPM), costs PPPM remained high in the second year ($12,976 PPPM) following HR-MDS diagnosis. Over the entire follow-up period, 62% of the total costs were due to MDS-related care (64% in year 1 and 54% in year 2). Although MDS-related costs decreased from the first to the second year of diagnosis, non-MDS-related costs remained relatively similar. This same trend of decreasing cost of treated patients over time has been noted in multiple myeloma (MM) as well. In a retrospective study composed of 1181 patients with newly diagnosed MM, the total monthly cost for patients declined steadily, from $15,734 per month during the first quarter of therapy initiation to $5082 per month for the period starting 18 months after initiation of therapy [15]. In our patient population, the higher MDS-related costs in the first year following HR-MDS diagnosis were consistent with a larger proportion of patients receiving MDS-related chemotherapy and supportive care. The decrease in costs observed in the second year after diagnosis was mainly driven by the MDS diagnosis being captured in the first year’s costs and fewer patients receiving treatments. Further, it should be noted that the cost of progression to AML in this HR-MDS population was not evaluated, as follow-up ended upon transformation to AML. In our study, 38.8% of our population progressed to AML, and these patients, along with those who died, incurred higher costs in the first year after diagnosis relative to patients who did not have these events. For non-MDS-related medical costs, inpatient hospitalizations were the main cost driver, accounting for 60% of costs.

Studies evaluating the economic burden of HR-MDS patients are limited. The cost of drugs alone for lower-risk MDS was estimated at an average of $63,577 per patient annually [16]. In our analysis, HMAs were the most frequently utilized first-line therapy, with approximately 90% of patients receiving an HMA; of these, most patients (69%) received azacitidine. This aligns with both the NCCN guidelines and the primary literature, which show that azacitidine improves overall survival in trial-selected HR-MDS patients, while decitabine has not demonstrated a survival benefit [4, 12‐14]. Further, the majority of patients in our analysis did not receive MDS-directed therapy beyond the first line, as transformations to AML and/or death were the predominant events that occurred during the follow-up period. A longitudinal analysis of elderly MDS patients utilizing the SEER database found that the 2-year cost from MDS diagnosis was higher in patients treated with HMAs versus those who did not receive HMAs [$92,102 vs $40,111, respectively (2009 US dollars)] [6]. Additionally, a retrospective analysis reviewing the use of transfusions and/or active therapy in MDS patients showed that patients were at highest risk for hospitalization when receiving both transfusions and active therapy [8]. However, neither of these previous studies accounted for IPSS-R risk category. Therefore, the results of this analysis add needed data regarding cost and healthcare utilization in an HR-MDS population.

MDS-related supportive care visits and costs were also higher in the first year of diagnosis compared to the second year of diagnosis. This result is slightly unexpected, as the use of HMAs is commonly associated with a decreased need for transfusions and supportive care, thereby leading to decreased costs [7, 17, 18].

Healthcare utilization and the associated medical costs in HR-MDS patients receiving treatment are high, with a cost of almost $18,000 PPPM. The medical costs associated with HR-MDS decreased from the first to the second year following HR-MDS diagnosis, coinciding with a decrease in healthcare utilization, in particular the administration of chemotherapy and supportive care. However, costs continued to remain high in the second year. As treatment of HR-MDS evolves, the economic impact and healthcare utilization need to be further investigated in this patient population.