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

Abstract

This study assessed underuse of treatment with hypomethylating agents (HMAs) among patients with newly diagnosed myelodysplastic syndromes with refractory anemia with excess blasts. Of 1190 patients from the Surveillence, Epidemiology, and End Results-Medicare database, 526 (44%) did not use HMAs and 295 (25%) were non-persistent HMA users, whereas 369 (31%) were persistent HMA users. Several clinical and demographic factors were associated with HMA underuse. 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, HMAepersistent users, and HMAenon-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.

A randomized phase 2 trial of azacitidine with or without durvalumab as first-line therapy for higher-risk myelodysplastic syndromes

“…Real-life analyses have suggested the survival among patients with HR-MDS treated with HMAs is only 11-17 months. [21][22][23] Therefore, a need exists for improved frontline therapy in patients with HR-MDS, ideally by adding non-myelosuppressive agents to the HMA backbone for this frail patient population. 24,25 To our knowledge, this is the first large, randomized trial of azacitidine with or without ICB reported in untreated patients with HR-MDS.…”

Blood and Marrow Transplant Clinical Trials Network Study 1102 heralds a new era in hematopoietic cell transplantation in high‐risk myelodysplastic syndromes: Challenges and opportunities in implementation

“…For alloHCT, it is known that physician (perception of risks and efficacy), system (insurance coverage), and patient (age, social support, financial, and comorbid illness) factors are determinants of referral practices 10 . Specifically for MDS, current evidence from a population‐based analysis indicates a low overall use of active treatment approaches including disease‐modifying therapies such as HMAs 11 . In a state‐wide prospective epidemiologic cohort study of newly diagnosed patients with MDS in Minnesota, Pease et al 12 observed divergent practice patterns across the state based on practice location.…”

Oral hypomethylating agents: beyond convenience in MDS

“…Real-world stud ies fur ther dem on strate the rel a tively lim ited ini ti a tion of HMA treat ment for high-risk patients, with only 12% to 30% of pre sum ably eli gi ble patients receiv ing ther apy at all , depending upon the report. 20,27,30 These data high light the fact that despite the avail abil ity of HMAs as pri mary ther apy for MDS for more than 15 years, many patients do not receive any ther apy at all , and among those who do, early dis con tin u a tion or inad e-quate dose inten sity dur ing early cycles prob a bly com pro mises response. 30 Such treat ment deci sions are likely to have an adverse impact on qual ity of life and com pro mise sur vival for those MDS patients, who will accrue all the tox ic ity from HMA ther apy and none of the ben e fits (HI, CR, or sur vival) of sustained ther apy.…”

“…20,27,30 These data high light the fact that despite the avail abil ity of HMAs as pri mary ther apy for MDS for more than 15 years, many patients do not receive any ther apy at all , and among those who do, early dis con tin u a tion or inad e-quate dose inten sity dur ing early cycles prob a bly com pro mises response. 30 Such treat ment deci sions are likely to have an adverse impact on qual ity of life and com pro mise sur vival for those MDS patients, who will accrue all the tox ic ity from HMA ther apy and none of the ben e fits (HI, CR, or sur vival) of sustained ther apy. 24 The impor tance of ade quate sup port and ther apy per sis tence for patients with higher-risk MDS can not, there fore, be overstated.…”

“…29 A more detailed anal y sis of this same cohort reveals that an addi tional 20% of patients had early dose delays of >90 days between cycles, which likely obvi ates response. 30 Overall, among the approx i ma tely 50% of patients with higher-risk MDS, those who did not receive their HMA on sched ule for at least 4 cycles had sub stan tially higher rates of health care uti li za tion char ac ter ized by increased emer gency room vis its, higher rates of hos pi tal i za tion, and more admis sions to skilled nurs ing facil i ties and hos pice. Suboptimally treated patients in this cohort were more likely to be older and unpartnered.…”