First-Line (1L) Treatment Patterns and Outcomes Among Patients With Newly Diagnosed Myelodysplastic Syndromes (MDS): A Global, Retrospective Observational Cohort Study

Topic: 10. Myelodysplastic syndromes - Clinical Background: Patients (pts) with myelodysplastic syndromes (MDS) often require ongoing red blood cell transfusions (RBCT) to counter persistent ineffective erythropoiesis. As new treatment options have become available, it is important to understand real-world clinical practice patterns and opportunities, to tailor clinical management to pts’ needs with the most effective and least burdensome therapeutic options. However, real-world first-line (1L) treatment patterns for MDS are not well understood in the context of pt characteristics, treatment duration, and subsequent clinical outcomes. Aims: This study aimed to describe the characteristics, 1L treatment patterns, and clinical outcomes of pts with lower-risk (LR)-MDS in a US and EU cohort. Methods: This was a retrospective study of adults (≥18 y of age) receiving 1L systemic treatment for LR-MDS (2014 or later). Pt data came from COTA Vantage data (US) and BC Platforms (EU; Estonia, Poland, and Greece). The index date (baseline) was the date of first systemic therapy for MDS after diagnosis. Eligible pts had Revised International Prognostic Scoring System (IPSS-R) classification of Very low-, Low-, or Intermediate-risk MDS and <5% blasts in bone marrow, serum erythropoietin level <500 U/L, and Eastern Cooperative Oncology Group (ECOG) performance score 0–2 on or before the baseline. Subgroups of interest included pts who received erythropoiesis-stimulating agents (ESAs) in 1L (single or combination therapy with ESA) or other 1L treatments (any non-ESA systemic therapy). Pt characteristics, treatment patterns, time to first positive hemoglobin (Hb) increase, and rates of secondary malignancies were assessed using descriptive statistics. Results: A total of 421 pts were included (US cohort, n=351; EU, n=70). Overall, median age was 75 y, 43% were female, and 85% were White; characteristics were generally similar for US and EU pts (Table). Nearly all pts had ECOG performance score ≤1 (81%). Median time from MDS diagnosis to 1L treatment was 1.6 mo. Most pts received ESAs in 1L treatment, for a median of 12.4 mo; 86% of the ESA in 1L group received ESA monotherapy. Median pre-baseline Hb levels were 9.2 g/dL (ESA in 1L group, 9.2 g/dL; other 1L treatments group, 10.1 g/dL). Overall, 42% of pts achieved an Hb increase ≥1.5 g/dL during 1L therapy (ESA in 1L group, 45%; other 1L treatments group, 33%), with a median time to achieving ≥1.5 g/dL Hb increase of 1.9 mo, and a median duration of response of 8.9 mo. Overall, 10% of pts progressed to high-risk MDS and/or acute myeloid leukemia (AML) a median of 13.7 mo after starting 1L treatment (ESA in 1L, 9%, median 16.0 mo; other 1L treatments, 10%, median 7.6 mo). Overall, 52% (n=219/421) of pts received any second-line (2L) treatment after discontinuing 1L treatment: ESA in 1L group (56%, n=183/324), median 7.1 mo; other 1L treatments group (37%, n=36/97), median 3.7 mo. Of the 183 pts in the ESA in 1L group who received 2L treatment, 135 (74%) received an ESA-containing regimen, of whom 78 (78/135, 58%) were retreated with ESA monotherapy. Summary/Conclusion: Pts with newly diagnosed LR-MDS in the US and EU cohorts had generally similar baseline clinical characteristics, including low Hb levels. Pts received either ESAs or other 1L treatment for >1.5 y on average, even though the majority did not achieve clinically meaningful Hb improvement. Pts who discontinued ESAs in 1L were often retreated with ESAs in 2L. These findings suggest a substantial need for more effective clinical management approaches to improve outcomes in 1L and 2L, and delay disease progression in LR-MDS.Keywords: Real world data, Hemoglobin, Myelodysplastic syndrome