Real-world patient characteristics, treatment patterns, and outcomes in patients with myelodysplastic syndromes

Abstract Background: Due to its rarity and heterogeneity, management of myelodysplastic syndrome (MDS) can be challenging. The Revised International Prognostic Scoring System (IPSS-R) estimates risk of mortality and transformation to acute myeloid leukemia (AML), defining 5 risk categories of very low, low, intermediate, high and very high, with lower-risk MDS (LR-MDS; very low, low, and intermediate risk) comprising about two-thirds of cases. LR-MDS management aims to mitigate cytopenia-related complications, and erythropoietin-stimulating agents (ESAs) have historically been a foundation of therapy. However, ESA usage and response rates vary greatly in current literature. In this study, we aim to describe the characteristics and treatment patterns of patients with MDS at Kaiser Permanente Northern California (KPNC), a large integrated health system. Methods: We conducted a retrospective cohort analysis of all adult patients with MDS diagnosed by bone marrow analysis at KPNC from 2019 through 2024. Data was collected via electronic medical record extraction and manual chart review. Patients were excluded if they had active non-MDS malignancy, history of kidney transplant, or history of end-stage renal disease requiring dialysis. IPSS-R score ≤4.5 was classified as LR-MDS and >4.5 as higher-risk MDS (HR-MDS). ESA failure was defined as lack of ≥1.5 g/dL rise in hemoglobin (Hgb) or no decrease in red blood cell (RBC) transfusion requirement 8 weeks after treatment initiation. Transfusion dependence (TD) was defined as requiring ≥1 RBC transfusion within an 8-week period. Conversely, transfusion independence (TI) meant requiring no RBC transfusions. Results: Among 561 patients with known IPSS-R risk scores, 418 (74.5%) had LR-MDS and 143 (25.5%) had HR-MDS. Median age at diagnosis was 75.4 years and Elixhauser Comorbidity Score (ECS) was 4. Patients were predominantly male (61.6%) and non-Hispanic White (64.9%). Median overall survival (OS) was 4.1 years in all LR-MDS patients and 0.9 years in HR-MDS; transformation to AML at 2 years occurred in 11.0% and 51.7%, respectively. Among LR-MDS patients, 30.6% received ESAs as 1st-line therapy while 24.8% received other treatments such as hypomethylating agents (9.8%), granulocyte-colony stimulating factor (2.4%), and luspatercept (2.6%); 44.5% received no treatment. ESA-treated patients were older than other or no-treatment patients (median age 78.5 years versus 73.3 and 74.5 years, respectively) and had more kidney dysfunction (eGFR<45 in 15.7% versus 6.9% and 4.3%, respectively). There were no significant differences in sex, race/ethnicity, or ECS between groups. Baseline Hgb was lower in treated (median 9.0 g/dL in both groups) compared to untreated patients (median 10.9 g/dL). Among the 35% of patients with recorded baseline erythropoietin, median values were 80.5 mU/mL, 241.0 mU/mL, and 34.5 mU/mL in the ESA, other, and no-treatment groups, respectively. Median OS in LR-MDS was 39.1 months with ESAs, 36.3 months with other treatments, and 65.8 months with no treatment, while 2-year AML transformation rate was 9%, 13%, and 6%, respectively. In LR-MDS patients who received 1st-line ESAs, 33.6% were TD prior to treatment initiation. Median time from diagnosis to treatment initiation was 31.5 days and treatment duration was 21.6 weeks. Of 121 patients (94.5%) with a minimum of 8 weeks follow-up after ESA start, 53.7% achieved TI for 16 consecutive weeks. ESA treatment failure occurred in 64.5%, and ESAs were continued for a median 13.1 weeks after failure. Discussion: At baseline, LR-MDS patients receiving ESAs were older with more kidney dysfunction and worse anemia compared to untreated patients. ESA-treated patients had longer OS and less AML transformation than patients receiving other treatments but worse outcomes than untreated patients. The OS in our ESA-treated LR-MDS patients was similar to outcomes seen in large US and European MDS registry data, though with some differences in AML transformation rates. Additionally, our ESA response rate fell within currently published ranges of 15 to 74%; this wide range likely reflects clinical and methodological heterogeneity. Overall, our findings illustrate the importance of real-world data to better understand LR-MDS treatment patterns and outcomes in different patient populations and clinical settings and highlight the importance of optimizing patient care through use of effective 1st-line therapies.