Transfusion Burden and Outcomes in Patients with Low- or Unspecified-Grade Myelodysplastic Syndromes Treated with Erythropoiesis-Stimulating Agents: Analysis of a United States Commercial Claims Database
Authors: Mehra Maneesha , Potluri Ravi , He Jianming , Rizo Aleksandra , Mundle Suneel , Bussolari Jacqueline 
Published: October 2019

Abstract
Introduction: Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders characterized by 1 or more peripheral blood cytopenias.Anemia is the most common cytopenia associated with low-grade MDS (based on the International Prognostic Scoring System). Erythropoiesis-stimulating agents (ESA) are commonly used as frontline treatment of anemia in patients (pts) with low-grade MDS; red blood cell transfusions are also important in supportive care. The present database analysis was conducted to understand the transfusion burden and outcomes among pts in the United States who were diagnosed with low- or unspecified-grade MDS and treated with ESA.
Methods: A retrospective analysis of theOptum integrated claims and Electronic Medical Record database ("Optum Database") identified pts aged ≥ 18 years with an index diagnosis of MDS (low-grade, ICD 9 code: 238.72; high-grade, ICD 9 code: 283.73; del(5q), ICD 9 code: 238.74; or unspecified-grade, ICD 9 code: 238.75) between 2006 and 2014 who had 365 days of retrospective data preceding index diagnosis. Pts with baseline acute myeloid leukemia were excluded. Demographics and clinical outcomes were analyzed by descriptive summary. Kaplan-Meier survival analysis was performed to define overall survival (OS) and time to transfusion dependence or transfusion independence.
Results: Among the 8,493 pts in the Optum Database who met the inclusion criteria, MDS was categorized as low-grade in 2,136 (25.2%), high-grade in 367 (4.3%), del(5q) in 198 (2.3%), and unspecified-grade in 5,792 (68.2%); median follow-up was 2.3 years. In each MDS category, roughly half of pts were male, and the majority were white and non-Hispanic. Median ages at diagnosis were 75, 74, 74, and 76 years, and 977 (46%), 224 (61%), 83 (42%), and 2,071 (36%) received ≥ 1 treatment in the low-grade, high-grade, del(5q), and unspecified-grade MDS categories, respectively. Frontline therapy with ESA was the mainstay of treatment for pts with low-grade (n = 732; 75%) and unspecified-grade (n = 1,284; 62%) MDS. Average durations of frontline treatment with ESA were 228.1 and 204.5 days in pts with low-grade and unspecified-grade MDS, respectively. Median OS among low- and unspecified-grade MDS pts receiving frontline ESA was 5.4 and 4.6 years, respectively. Of the pts who received frontline ESA, 53 (7.2%) with low-grade and 107 (8.3%) with unspecified-grade MDS were transfusion dependent (≥ 2 transfusions in the 16 weeks prior to treatment initiation). Transfusion dependence in pts receiving frontline ESA was associated with shorter median OS vs transfusion independence (1.7 years vs 5.7 years in low-grade MDS, P < 0.0001; 1.7 years vs 5.2 years in unspecified-grade MDS, P < 0.0001;Figure 1). Among the 160 frontline ESA pts with low-/unspecified-grade MDS who were transfusion dependent, 108 (68%) became transfusion independent (defined as ≥ 60 days without transfusion; 37 of 53 with low-grade MDS; 71 of 107 with unspecified-grade MDS); median time to transfusion independence was 137 and 139 days in pts with low-grade and unspecified-grade MDS, respectively. Most pts with low- or unspecified-grade MDS who received frontline ESA (52% and 51%, respectively) went on to receive second-line treatment, and treatment with ESA was the most common second-line therapy (42% and 40%, respectively). 163 (8.7%) of post-front-line ESA pts were transfusion dependent. Among pts with low-/unspecified-grade MDS who received second-line therapy, median OS was shorter for those who were transfusion dependent after frontline treatment with ESA vs those who were transfusion independent (1.97 years vs 4.5 years, respectively, P < 0.001). 92 (56%) of these transfusion-dependent pts became transfusion independent in a median of 181 days.
Conclusions: ESA therapy was the most common treatment approach, both frontline and second-line, for pts with low- or unspecified-grade MDS; however, treatment with ESA did not always eliminate the need for transfusion. Similar to previous reports in pts with low-grade MDS, survival outcomes were substantially worse if pts were transfusion dependent prior to frontline or second-line treatment or became transfusion dependent following frontline treatment. These data indicate the critical importance for treatments to reduce transfusion burden among pts with MDS, in both the frontline and relapsed settings.

Disclosures
Mehra: Janssen: Employment, Equity Ownership. Potluri:Janssen Research & Development, LLC: Other: Contracted to perform research; SmartAnalyst, Inc.: Employment. He:Janssen Global Services, LLC: Employment, Equity Ownership. Rizo:Janssen Research & Development, LLC: Employment, Equity Ownership. Mundle:Janssen Research & Development, LLC: Employment, Equity Ownership. Bussolari:Janssen Research & Development, LLC: Employment, Equity Ownership.