Lower-Risk MDS: The Value of Early Luspatercept Use

Patients diagnosed with lower-risk myelodysplastic syndromes (MDS) who rely on red blood cell (RBC) transfusions tend to have lower overall survival rates, reduced quality of life (QOL), and higher healthcare resource utilization compared with those who do not require transfusions or have a lower transfusion frequency.

In the first-line (1L) treatment of transfusion-dependent, lower-risk MDS, erythropoietin-stimulating agents (ESAs) are commonly used. Luspatercept, approved by the European Medicines Agency for patients who do not respond to or cannot tolerate ESAs (MEDALIST trial), is currently under investigation as a potential treatment option for all patients (COMMANDS trial). This investigation aimed to assess luspatercept administration’s impact on health outcomes and healthcare resource utilization in patients with lower-risk MDS. It compared its use as a 1L treatment versus a second-line (2L) treatment.

A model based on discrete-event simulation was developed to compare treatment outcomes for RBC-transfusion dependent patients starting from 1L treatment initiation throughout their lifetime. Pathway A involves luspatercept in 1L and standard of care in 2L, while pathway B includes ESA in 1L, followed by luspatercept in 2L. The probabilities of achieving a T6 reduction response in 1L and 2L were determined using data from the COMMANDS and MEDALIST trials. Furthermore, a scenario analysis was performed to evaluate the outcomes of responding to luspatercept in 1L but not in 2L (pathway A) versus responding to luspatercept in 2L but not in 1L (pathway B).

The transfusion burden (TB) reduction response included patients who achieved RBC transfusion independence (RBC-TI) for more than 12 weeks after starting treatment and those who achieved ≥50% TB reduction but did not reach RBC-TI within the initial 24 weeks of treatment. The model considered the response to decline over time.

Patients would move on to the following treatment line following nonresponse or loss of response to 1L treatment. In cases of nonresponse or loss of response to 2L treatment, patients would transition to the best supportive care and return to their baseline level of TB for the remainder of their lives. The model suggested that lower TB and RBC-TI were associated with enhanced survival and QOL, as well as reduced complications and healthcare resource utilization, based on trial data (COMMANDS, MEDALIST) and literature model input data.

According to the model base case, patients treated with luspatercept in the 1L and standard-of-care pathways are projected to have a life expectancy that is 5.3 months longer compared with those who receive luspatercept in the 2L pathway and ESA in the 1L pathway. Additionally, they are expected to experience an increase of 4.9 months in quality-adjusted life and require 1.5 fewer transfusions per year. The number of hospitalizations and emergency department visits is also anticipated to be lower for patients in the 1L pathway, with a reduction of 0.3 trips for both. In the scenario analysis comparing responders to luspatercept in 1L versus 2L, notable improvements in life expectancy and quality-adjusted life are projected.

Based on the model findings, initiating luspatercept treatment early in the therapeutic process brings advantages in survival, quality-adjusted survival, and disease burden. Additionally, attaining a response to luspatercept in the 1L of treatment as opposed to the 2L results in significant enhancements in health and disease burden outcomes.

Source: Valcárcel D, Coughlan A, Klijn S, et al. Value of early luspatercept in lower-risk myelodysplastic syndromes (LR-MDS). Madrid, Spain, & online: presented at EHA2024 Hybrid Congress; abstract P789.