New research underscores the substantial economic burden associated with early discontinuation of guideline-recommended hypomethylating agent (HMA) therapy among patients with refractory anemia with excess blasts, a diagnosis that substantially overlaps with higher-risk myelodysplastic syndrome (MDS).
New research published in Clinical Lymphoma, Myeloma, and Leukemia underscores the substantial economic burden associated with early discontinuation of guideline-recommended hypomethylating agent (HMA) therapy among patients with refractory anemia with excess blasts (RAEB), a diagnosis that substantially overlaps with higher-risk myelodysplastic syndrome (HR-MDS).
HMAs are recommended therapeutic options for patients with HR-MDS because they have been associated with survival benefit, improved quality of life, and improvement in cytopenias, which leads to delayed progression to acute myeloid leukemia.
“In order to elicit clinical response, HMA treatment is recommended to be provided to patients for least 4, or even 6, treatment cycles,” the authors wrote, while “premature treatment discontinuation or suboptimal treatment is likely to affect clinical and economic outcome.”
However, difficulties ensuring treatment cycles are administered as scheduled have been reported, with one study finding a reported delay in 31% of scheduled cycles among patients with MDS and other hematologic disorders.
To estimate and compare the economic impact of HMA nonpersistence in patients with HR-MDS who received the treatment, researchers conducted a retrospective observational cohort analysis. Patient data, recorded between 2010 and 2016, were gleaned from the Surveillance, Epidemiology, and End Results (SEER)-Medicine linked database.
Within the data set, demographic and clinical characteristics, regional cancer registry data, and information on cause of death for those with cancer are linked to Medicare claims.
All individuals included in the analysis were diagnosed with MDS and subsequently initiated HMA treatment. As RAEB is a histologic designation that often overlaps with HR-MDS, the International Prognostic Scoring System (IPSS) code for RAEB was used to determine diagnoses.
In addition, “Patients were required to be ≥ 66 years of age at diagnosis and continuously enrolled in Medicare Parts A and B for ≥ 12 months before initial MDS diagnosis until the end of the study period, which was defined as censoring, death, or December 31, 2016, whichever occurred first.” Patients’ health care resource use (HCRU) was also assessed, and associated costs were calculated as per patient per month (PPPM), inflated to 2018 US$.
A total of 664 patients were included in the final analysis, of whom 369 (55.6%) were persistent with HMAs and 295 (44.4%) were nonpersistent—defined as receiving fewer than 4 cycles of HMA treatment or having a gap (≥90 days) in cycles.
A weighted generalized linear model (GLM) analysis found “the HMA non-persistent group incurred significantly (P < .05) higher total PPPM costs compared to the HMA-persistent group ($18,039 vs $13,893), particularly for hospitalization ($3375 vs $2131), and emergency room ($5517 vs $2867) costs.”
An inverse probability of treatment weight–weighted regression analysis also showed PPPM resource utilization was significantly higher among HMA-nonpersistent patients for hospitalizations, emergency use visits, and receipt of care via home health, hospice, or skilled nursing facility compared with persistent patients. However, the rate of outpatient and physician visits was significantly higher among HMA-persistent patients.
Investigators also found “sensitivity analysis among patients who were alive for ≥ 4 months suggested that HMA-non-persistent patients had higher utilization rate for emergency room visits, hospitalizations, home health, hospice care, and skilled nursing facility.”
Among nonpersistent patients, there was a significantly higher proportion of older patients and individuals without a partner compared with the HMA-persistent group. According to researchers, this finding suggests these patient subgroups may need support to continue with their treatment cycles.
The data used in the study did not include reasons for HMA treatment discontinuation, marking a limitation. Authors also cautioned findings may not be generalizable as only those 66 years and older were included in the study.
“The high proportion of patients in the HMA-non-persistent group warrants closer care management to achieve better outcomes and reduced healthcare spending,” they concluded.
Joshi N, Kale H, Corman S, Wert T, Hill K, Zeidan AM. Direct medical costs associated with treatment non-persistence in patients with higher-risk myelodysplastic syndromes receiving hypomethylating agents: a large retrospective cohort analysis. Clin Lymphoma Myeloma Leuk. Published online December 8, 2020. doi:10.1016/j.clml.2020.12.002