Treatment Patterns and Outcomes Among Patients with Higher-Risk Myelodysplastic Syndromes Treated in a Real-World Setting: Electronic Medical Record-Based Data

Abstract

Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders resulting in ineffective hematopoiesis primarily affecting older adults; median age of diagnosis is >70 years. Treatment decisions in MDS are largely based on a prognostic scoring system that has been incorporated into some drug labeling (NCCN 2016). The use of hypomethylating agents (HMAs) in patients with higher-risk (HR) MDS is supported by consensus guidelines, thus the purpose of this study was to examine factors influencing prescribing patterns in this subset of patients.Methods: This was a retrospective cohort study using a large United States electronic medical record database. Newly diagnosed HR MDS patients initiating first-line therapy (1LT) between 1/2008 and 7/2015 were followed for 1 year prior to and ≥ 60 days after diagnosis. Included patients were ≥18 years old with evidence of HR MDS identified as follows: 1) ≥1 inpatient claim with an HR MDS diagnosis code (ICD-9 code: 238.73; ICD-10 codes: D46.20, D46.21, D46.22), or 2) ≥2 outpatient claims with an MDS diagnosis code, with the first one coded for HR MDS ≥60 days but <1 year apart during the identification period. The date of the first HR MDS claim served as the index diagnosis date. 1LT was defined as an MDS-specific systemic agent initiated on or after the index diagnosis date and included all agents received within 30 days following the first infusion or fill date. Subsequent lines of therapy (LOT) were defined as an addition of a new MDS-specific agent >30 days after the initial chemotherapy agent(s) or a switch to another drug combination. Stem cell transplantation (SCT) was considered part of the LOT in which it occurred. All patients were followed until death or progression to acute myeloid leukemia (AML), loss to follow-up, or the end of study period (9/30/2015).Results: 345 patients newly diagnosed with HR MDS met the study criteria; 218 (63%) were treated with supportive care (including transfusions, hydroxyurea, colony-stimulating factors [CSFs], azole antifungals, erythropoiesis-stimulating agents [ESAs], or pain medications) or observation only and 127 (37%) were treated with MDS-directed therapy (HMAs, immunosuppressive therapy, induction-type therapy, SCT, or lenalidomide) ± supportive care (Table 1). Compared to untreated patients, a greater proportion of treated patients were male, had severe cytopenias (specifically, neutrophils <0.8 K/L and/or platelets <50 K/L), and had received a transfusion of either red blood cells or platelets during the baseline period (Table 1). In the treated population, most patients received only 1LT (n=111, 87%); 16 patients (13%) went on to second-line therapy, and 3 (2.3%) to third-line therapy. HMAs were the most utilized agents in 1LT, with 84 (66%) and 29 (23%) patients receiving azacitidine and decitabine, respectively. Lenalidomide was used in 6.3% of patients (n=8), and induction-type chemotherapy in 3.2% (n=4); no patients received immunosuppressive therapy only (cyclosporine or anti-thymocyte globulin). At median follow-up of 9 months (interquartile range [IQR]: 4, 16) for the treated population, 46 (36%) had died and 36 (28%) had progressed to AML. Within the population that received an HMA (n=113), age ≥75 years was approximately 50% for each agent; however, a greater proportion of patients who received azacitidine had a known marrow blast count of >5%, hemoglobin <10 gm/dL, and platelets <50 K/L at baseline (Table 2). At end of follow-up, 27% (n=23) and 36% (n=30) of azacitidine-treated patients had progressed to AML or died whereas 28% (n=8) and 41% (n=12) of decitabine-treated patients progressed to AML or died, respectively.Conclusions: Despite the existence of treatment guidelines for HR MDS patients and given the limitations of a retrospective study, the majority of patients in a real-world setting are not treated with MDS-specific agents. Younger age (<75 years) and more severe cytopenias may be factors considered in the decision of whether or not to treat HR MDS. If treated, HMAs are the most utilized therapy in these patients, with azacitidine predominating. Cytopenias at baseline may also influence the choice between azacitidine and decitabine, although survival and progression to AML appear similar between groups.