Improvement in Quality of Life in MDS Patients Who Become Transfusion Independent after Treatment
Authors: Wan Bo , Alibhai Shabbir MH , Chodirker Lisa , Mozessohn Lee , Geddes Michelle , Zhu Nancy , Trottier Amy , St-Hilaire Eve , Finn Nicholas , Leber Brian , Khalaf Dina , Christou Grace , Sabloff Mitchell , Leitch Heather A , Shamy April , Yee Karen , Storring John M. , Nevill Thomas J. , Houston Brett L. , Elemary Mohamed , Delage Robert , Parmentier Anne , Siddiqui Mohammad , Mamedov Alexandre , Zhang Liying , Buckstein Rena 
Published: December 2024

Introduction: Patients with myelodysplastic syndromes (MDS) generally experience inferior quality of life (QOL), in part due to transfusion dependent-anemia and. Many studies have shown that patients who are transfusion dependent (TD) typically have worse QOL compared to patients who are transfusion independent (TI), but the impact of achieving TI once TD on patient QOL is uncertain. MDS-CAN is a prospective multicentre Canadian registry that captures longitudinal clinical and QOL ‘real-world’ data in patients with MDS. We used the MDS-CAN registry to provide additional insight into the association between changes in transfusion status (i.e., from TD to TI, or from TI to TD) or stability of transfusion state (TI and TD) with overall survival (OS) and QOL.
Methods: We conducted a retrospective cohort analysis of red blood cell (RBC) transfusion status over time and examined its impact on OS and patient reported outcomes in patients prospectively enrolled in the MDS-CAN registry (NCT02537990). In brief, enrollment started in 2006 and included patients who were ≥ 18 years old with a diagnosis of MDS, MDS/MPN, or low blast count AML (20-30%). The four transfusion groups were defined as TD to TI (Group A), TI to TD (Group B), and maintaining TD (Group C) or TI (Group D).
We obtained data on demographics, disease, function, frailty, laboratory parameters, as well as longitudinal data on treatment, transfusions, and patient-related health outcomes using validated instruments assessing QOL. The earliest QOL score obtained after initiation of treatment was considered the baseline for each patient. In group A and B, this was compared to the QOL score obtained at the first instance after a change in transfusion status. To be consistent, the median time to change in transfusion status in group A and B was used to select the comparator QOL time point in groups C and D. Wilcoxon rank-sum or Kruskal-Wallis nonparametric test, Chi-square or Fisher exact test were applied to compare continuous or categorical demographic and treatment characteristics, as appropriate. A general linear mixed model was used to identify significant associations between QOL scores and the 4 transfusion health states. Kaplan-Meier overall survival (OS) curves from diagnosis were conducted in each of the four groups (A, B, C, and D), in patients treated with hypomethylating agent (HMA), and in patients treated with erythropoietin stimulating agonist (ESA).
Results:
Of 1120 patients included from the MDS-CAN registry, 759 were treated with either an HMA, lenalidomide or ESA. Longitudinal QOL analysis of the 656 patients who received treatment and provided serial QOL data included 54, 151, 126, and 326 patients in groups A-D, respectively. Overall QOL significantly improved in Group A, with trends towards improved component scores in physical and social function. In Group B, there were significant decreases from baseline to the first QOL after TD across multiple QOL measures on several instruments including worse global QOL, worse fatigue as well as worse physical, role, and social functioning. Group C had significantly more fatigue; group D had significant but milder deteriorations across global QOL, fatigue, physical and role functioning.
Survival curves for all registry patients (n=1120) and the HMA-treated cohort (n=427) demonstrated superior OS in patients in group D. This was followed by groups A and B with similar OS to each other and was the lowest in group C (p&lt;0.001 for both curves). These differences in OS were observed after 36 months of follow up. There were no differences in survival between the four groups among those who received ESA.
Conclusion:
Patients with MDS receiving treatment who achieved TI had improvements in patient-reported overall QOL but not in all individual metrics. Loss of TI was associated with a greater negative impact on overall QOL, with significance extending across multiple domains of physical, role, and emotional function. Among patients who remained TI, there was a trend of gradually reduced QOL over time. Patients who remained TI had superior OS, and patients who remained TD had inferior OS. There was intermediate OS in patients who had a change in transfusion status of either direction.