VALUE OF EARLY LUSPATERCEPT USE IN LOWER-RISK MYELODYSPLASTIC SYNDROMES

Abstract

Objective: Patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) who are red blood cell (RBC) transfusion dependent (RBC-TD) have lower overall survival and quality of life and higher healthcare resource utilization (HCRU) than pts who are transfusion independent (TI)/have a low transfusion burden (TB). An established treatment (tx) for TD LR-MDS is erythropoietin-stimulating agents (ESAs). Luspatercept is approved by the European Medicines Agency and US Food and Drug Administration for tx of anemia in pts with LR-MDS refractory to/ineligible for ESAs (MEDALIST trial) and for ESA-naïve pts requiring RBC transfusion (COMMANDS trial). This study estimates disease and HCRU burden associated with first-line (1L) vs second-line (2L) luspatercept tx in LR-MDS. Materials and methods: A discrete-event simulation-based model was developed to compare outcomes between tx pathways starting from 1L tx initiation over a lifetime for pts who are RBC-TD at baseline: pathway A) luspatercept in 1L and standard of care in 2L and pathway B) ESA in 1L and luspatercept in 2L. In each pathway, the probabilities of experiencing a TB reduction response to tx were based on data from the COMMANDS (1L) and MEDALIST (2L) trials. A scenario analysis was conducted to assess the outcomes of achieving response to luspatercept in 1L and no response in 2L (pathway A) vs response to luspatercept in 2L and no response in 1L (pathway B). TB reduction response included pts who achieve RBC-TI for ≥12 weeks (wk) since tx initiation and pts who achieve ≥50% TB reduction but not RBC-TI within the first 24 wk of tx. Loss of response was modeled over time. After lack/loss of response to 1L tx, pts initiate the 2L. After lack/loss of response to 2L tx, pts initiate best supportive care and revert to baseline TB for the remainder of their lifetime. Compared with higher TB, lower TB and RBC-TI in the model are associated with improved survival, quality of life, and disease and HCRU burden per trial (COMMANDS, MEDALIST) and literature model input data. Results: This model predicts that pts in pathway A vs B live 5.3 (11%) months (mo) longer, experience 6.8 (43%) more mo of life as RBC-TI, 4.9 (13%) more quality-adjusted mo of life, and on average receive 1.5 (11%) fewer RBC units annually. Annual number of hospitalizations and emergency department (ED) visits are each predicted to be 0.3 (5%) fewer for pts in pathway A. In the scenario analysis comparing responders to luspatercept in 1L vs 2L, substantial improvement in mo of life (18.1 [45%] mo), mo of life as RBC-TI (23.2 [528%] mo), and quality-adjusted mo of life (16.3 [53%] mo) are predicted. A reduction in annual number of hospitalizations, ED visits, and RBC units are predicted for responders to luspatercept in 1L vs 2L, (1.2 [19%] and 1.0 [18%] fewer visits, respectively, and 6.9 [39%] fewer RBC units). Discussion: This model suggests that receiving luspatercept early in the tx pathway leads to survival and quality-adjusted survival benefits and improved HCRU. Reduced hospitalizations, ED visits, and RBC transfusions thus reduce disease burden. C onclusion: Receiving and responding to luspatercept in 1L vs 2L leads to substantial improvement in health outcomes and disease burden. Increased use of luspatercept tx in 1L will allow more pts with LR-MDS to receive these benefits. Support: Bristol Myers Squibb. Abstract previously presented at EHA Annual Congress (Valcárcel D, et al. Hema Sphere 2024;8[suppl 1]:P789).