Patient Preferences for Benefits, Risks, and Administration Route of Hypomethylating Agents in Myelodysplastic Syndromes.

INTRODUCTION/BACKGROUND: Therapy with infused or injected hypomethylating agents (HMAs) may lead to higher treatment administration burden (ie, local reaction, visit frequency and duration) vs. oral HMAs.   OBJECTIVES: To reveal preferences of US and Canadian patients with myelodysplastic syndromes (MDS) for HMAs' benefits, risks, and administration burden through an online discrete-choice experiment (DCE). MATERIALS AND METHODS: Choice of DCE attributes and survey development were informed by literature review and interviews with clinicians, MDS patients, and caregivers serving as patient proxies, and patient advocacy groups (PAGs) representatives, including from AAMAC, AAMDS, and MDSF. DCE choice tasks were analyzed using random parameter logit models. Survey patients were recruited by the PAGs via their networks. To understand key preference drivers and how much patients were willing to trade between attributes, we calculated each attribute's relative attribute importance (RAI) and marginal rates of substitution. RESULTS: One hundred eighty-four respondents (including 158 patients; mean age, 67.2 years; male, 50.5%; White, 50.5%; US residents, 88%) completed the survey. MDS risk was low (34.8%), high (30.9%), or unknown (34.2%). RAI (in decreasing order) was as follows: risk of AML (40%), fatigue level (33%), number of visits (12%), mode of administration (6%), visit duration (5%), and administration frequency (4%). Assuming the same risk of AML transformation or level of fatigue, most respondents (76.6%) were predicted to switch to an oral pill if it were available to them. CONCLUSION: Given equivalent effectiveness across HMAs, patients' preferences for HMA administration method should be considered in treatment decision-making to minimize burden and facilitate adherence.

Persistence to hypomethylating agents and clinical and economic outcomes among patients with myelodysplastic syndromes.

OBJECTIVES: To evaluate hypomethylating agent (HMA) persistence in patients with myelodysplastic syndromes (MDS), and examine its association with healthcare resource utilization (HRU) and progression to acute myeloid leukemia (AML). METHODS: A total of 2,400 adults diagnosed with MDS initiating HMAs were included from IBM MarketScan databases during 1/1/2011-3/31/2018. The index date was HMA initiation following MDS diagnosis. Patients were classified according to their persistence status by the end of a fixed 'landmark period' of 4 months post-index. RESULTS: Median persistence to HMAs was 5.6 months (95% CI: 5.2, 6.1); HMA non-persistence increased with time. Non-persistent patients had a significantly higher non-HMA-related HRU burden than persistent patients [adjusted incidence rate ratios, outpatient visits: 1.12 (95% CI: 1.10, 1.14); inpatient visits: 1.48 (95% CI: 1.30, 1.69); emergency department visits 1.30 (95% CI: 1.12, 1.50); all p-values < 0.001]. All-cause and HMA-related outpatient visits were lower among non-persistent patients, likely because of fewer HMA administration-related visits. The incidence rate of AML was numerically, although not significantly, higher in non-persistent patients, when starting follow-up at the end of the landmark period. When follow-up began at the index date, non-persistent patients had a significantly higher rate of AML [adjusted hazard ratio, 1.88 (95% CI: 1.53, 2.32); p-value < 0.001]. CONCLUSIONS: HMA non-persistence, which increased over time, was associated with significantly higher non-HMA-related HRU, and numerically higher AML progression in MDS patients initiating HMAs. Future studies should evaluate predictors of HMA non-persistence in this patient population.

Direct Medical Costs Associated With Treatment Nonpersistence in Patients With Higher-Risk Myelodysplastic Syndromes Receiving Hypomethylating Agents: A Large Retrospective Cohort Analysis.

BACKGROUND: Suboptimal use of hypomethylating agents (HMAs) among higher-risk myelodysplastic syndrome (HR-MDS) patients can translate into worse health outcomes and economic burden. We estimated the direct medical costs associated with HMA treatment nonpersistence among HR-MDS patients. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, a retrospective cohort of patients diagnosed with refractory anemia with excess blasts (RAEB), a diagnosis that substantially overlaps with HR-MDS, between January 2011 and December 2015 was analyzed. Patients who had ≥ 1 year of continuous Medicare enrollment before diagnosis and who did not receive stem cell transplant or lenalidomide in the follow-up period were included. Patients receiving HMAs were stratified into HMA persistent (≥4 HMA cycles) and HMA nonpersistent (<4 cycles or a gap of ≥ 90 days between cycles) groups. Healthcare resource use and costs during the follow-up period were reported descriptively as total and per patient per month (PPPM). Weighted generalized linear models (GLM) were used to compare estimated healthcare resource use and costs between HMA groups. RESULTS: Among the 664 patients with RAEB, 295 (44.4%) were HMA nonpersistent and 369 (55.6%) HMA persistent. On the basis of weighted GLM analysis, the HMA nonpersistent group incurred significantly (P < .05) higher total PPPM costs compared to the HMA persistent group ($18,039 vs. $13,893), particularly for hospitalization ($3,375 vs. $2,131), and emergency room ($5,517 vs. $2,867) costs. CONCLUSION: There is a substantial economic burden associated with early discontinuation of guideline-recommended HMA therapy in RAEB patients. The study findings necessitate closer care management in this population in order to improve outcomes and reduce healthcare spending.

Under-use of Hypomethylating Agents in Patients With Higher-risk Myelodysplastic Syndrome in the United States: A Large Population-based Analysis.

BACKGROUND: Recent data suggest significant underutilization of hypomethylating agents (HMAs) that are recommended treatments for patients with myelodysplastic syndromes (MDS) with refractory anemia with excess blasts (RAEB). The study objective was to assess the degree of HMA use and predictors of HMA underuse in this population. PATIENTS AND METHODS: This was a retrospective study including patients diagnosed with the RAEB form of MDS between January 2011 and December 2015 using the Surveillance, Epidemiology, and End Results-Medicare linked database. Patients were excluded if they had < 1 year of continuous enrollment before diagnosis or received stem cell transplant or lenalidomide during the follow-up period. HMA non-peristence was defined as use of < 4 cycles (3-10 HMA days/28 days) of HMAs or a gap of ≥ 90 days between consecutive cycles. Patients were characterized as HMA never-users, HMA-persistent users, and HMA-non-persistent users. Descriptive statistics were used to summarize patient characteristics. Multivariable logistic regression was used to assess predictors of HMA underuse and persistence. RESULTS: Of the 1190 patients, 526 (44%) were never-users, 295 (25%) were non-persistent users, and 369 (31%) were persistent users. Age at diagnosis (eg, 66-70 years vs. ≥ 80 years; odds ratio [OR], 2.36; 95% confidence interval [CI], 1.56-3.56), marital status (single vs. married; OR, 0.67; 95% CI, 0.51-0.89), National Cancer Institute comorbidity index (≥ 3 vs. 0-1; OR, 0.62; 95% CI, 0.46-0.83), and performance status (poor vs. good; OR, 0.67; 95% CI, 0.51-0.87) were significantly associated with HMA underuse. CONCLUSION: Several demographic and clinical factors were associated with underuse of HMAs. There is need for a better understanding of suboptimal HMA use and its relationship with clinical response.