A Prospective Evaluation of Impact of Disease, Treatment, Sex, and Race Disparities on Quality of Life and Financial Toxicity in Patients with Myelodysplastic Syndromes
Authors: Ball Somedeb , Al Ali Najla H. , Jain Akriti G. , Shahzad Moazzam , Whiting Junmin , Lastorino Daniel , Xie Zhuoer , Walker Alison R. , Chan Onyee , Padron Eric , Kim Jongphil , Lancet Jeffrey E , Sallman David , Tinsley-Vance Sara M. , Komrokji Rami S. 
Published: December 2024

Introduction
Myelodysplastic syndrome (MDS) is primarily seen in non-Hispanic (NH) White males. Hence, data is scarce on race and sex disparities in patients (pts) with MDS. Pt-reported quality of life (QoL) is considered a clinically meaningful endpoint in MDS clinical trials; however, knowledge is lacking on impact of various pt, disease, and treatment-related factors on QoL and financial burden. Here we report the data from a prospective study evaluating potential predictors of QoL and financial toxicity in MDS, with particular reference to pt sex and race.
Methods
In this single-center prospective observational study, eligible consenting pts with MDS completed two surveys at 4-month interval. We assessed pt QoL with the Quality of Life in Myelodysplasia Scale (QUALMS), a validated MDS-specific 38-item tool, with potential score range of 0 (worst) to 100 (best). Financial burden was evaluated with 12-item Comprehensive Score for financial Toxicity (COST) questionnaire, with score range of 0 (worst) to 44 (best). Electronic medical records were reviewed to collect relevant clinical data on pts.
Results
From April 2022 till November 2023, we accrued 117 pts with MDS, including 72 (61.5%) male and 45 (38.5%) female pts. Overall, 88 (75%) were White, 14 (12%) Black, 7 (6%) identified as Asian; and 21 (18%) were Hispanics (H). Median age at diagnosis was 69 years. Median hemoglobin (Hb) level was 9.5 gm/dL and 30% of pts were transfusion dependent. Overall, 22% of pts had higher-risk disease by revised international prognostic scoring system. Common mutations included SF3B1 (30%), TP53 (19%), TET2 (18%), and ASXL1 (18%). At baseline, pts were on observation (Obs) (27%), erythropoiesis stimulating agents (ESA) (13%), luspatercept (Luspa) (9%), lenalidomide (Len) (5%), hypomethylating agent (HMA)-based therapy (27%), or clinical trial (11%). Mean baseline QUALMS score was 62 (range, 22-100) and COST score was 25.5 (range, 0-44) in the study pts.
Female pts were younger at diagnosis than males (median age- 65.5 vs. 71.5 years; p &lt;0.01). Male pts more commonly harbored RUNX1 mutation (16% vs. 2%; p=0.02) and were red blood cell (RBC) transfusion dependent than females (39% vs. 16%; p&lt;0.01). Therapy related MDS was relatively common in females (25% vs. 10%; p=0.03). We did not observe any significant differences in QUALMS and COST scores between male and female participants.
Among racial and ethnic groups, median platelet count was lower in pts of other race/ethnicity vs. NH White (93.5k vs. 140k; p&lt;0.01), and in H vs. NH (89k vs.128k; p=0.01). Rate of leukemic transformation was higher in H than NH group (24% vs. 8%; p=0.03). Black pts were younger at diagnosis (65.5 vs. 70 years; p=0.04), and had greater physical burden indicated by lower mean QUALMS-P score than White (46.7 vs. 58.2; p=0.03). Mean baseline COST score was significantly lower (i.e., greater financial toxicity) in other race/ethnicity vs. NH White (22.8 vs. 27.3; p=0.04), and in Black vs. White (16.9 vs. 27.2; p&lt;0.01).
Anemia (Hb &lt;10 gm/dL) was associated with a lower mean QUALMS (anemic vs. non-anemic- 58.7 vs. 67.6; p&lt;0.01) and QUALMS-P scores. Transfusion dependence was also associated with greater physical burden (mean QUALMS-P: 49.7 vs. 59.2; p=0.01). Pts on any treatment had lower mean QUALMS-P than those on Obs (Obs vs. ESA/Luspa/Len vs. HMA-based: 65.5 vs. 52.4 vs. 51.1; p&lt;0.01). Similarly, Hb &lt;10 gm/dL, RBC transfusion requirement, and HMA-based therapy were associated with lower mean COST scores. Pts with lower baseline QUALMS scores were likely to need transfusions and get hospitalized before follow-up survey. A higher average emotional burden (QUALMS-E) score across two timepoints was associated with better leukemia free survival (LFS) and overall survival (OS) in univariate Cox proportional model analysis (LFS- HR- 0.94, p &lt;0.01; OS- HR 0.94, p=0.04).
Conclusions
Our prospective study provides important insights into sex and race differences in MDS. Female and Black pts were younger at diagnosis, and male pts were more likely to require RBC transfusions. Hispanics had a higher rate of leukemic transformation, and Black pts experienced greater physical and financial burden than White population. Anemia, transfusion dependence, and higher intensity therapy were associated with worse QoL and financial wellbeing in pts. To our knowledge, this is the first prospective study addressing sex and race impact on QoL and financial toxicity in MDS.