HRQoL and vulnerability analysis from the National MDS Natural History Study

For many patients with myelodysplastic syndromes (MDS), treatment aims to improve health-related quality of life (HRQoL) factors as well as improving survival.¹ Patients with higher-risk MDS may have worse HRQoL. The risk of health deterioration or vulnerability is another important factor that may be associated with HRQoL in patients with MDS, and can be captured by patient-administered questionnaires such as the Vulnerable Elders Survey (VES-13).¹ The prevalence of vulnerability, and the impact of vulnerability on HRQoL, are not known in patients with MDS.¹

The National MDS Natural History Study (NCT02775383), which has been previously reported by the MDS Hub, is a prospective initiative enrolling patients with cytopenia to be assessed for MDS or MDS/myeloproliferative neoplasms (MPN). Abel et al.¹ recently published a HRQoL and vulnerability analysis from the National MDS Natural History Study in Blood Advances, which we are pleased to summarize below.

Study design and patient characteristics

An overview of the study design has been previously reported by the MDS Hub. This analysis focuses on the 449 patients with baseline HRQoL and vulnerability data available. Patients enrolled after March 27, 2020, were excluded to prevent any potential effect of the COVID-19 pandemic on results. The HRQoL instruments used in this analysis included:

• The MDS-specific 38-item Quality of Life in Myelodysplasia Scale (QUALMS)
• The 27-item Functional Assessment of Cancer Therapy-General form (FACT-G)
• The 7-item Patient Reported Outcomes Measurement Information System (PROMIS) Short Form-Fatigue
• The 5-item EuroQol 5-Dimension 5-Level (EQ-5D-5L)

Vulnerability was measured using the 13-item VES-13. Higher values in the QUALMS, FACT-G, and EQ-5D-5L scores indicate better HRQoL, while lower PROMIS Fatigue T-scores are associated with symptoms of fatigue; a VES-13 total score ≥3 indicates vulnerability. Patients were classified as having MDS, MDS/MPN, idiopathic cytopenia of undetermined significance, acute myeloid leukemia with <30% blasts (AML <30%), or at-risk based on bone marrow assessment. The majority of patients in this study were white (93%; p = 0.002) and non-Hispanic or Latino (95%; p = 0.069). Patient baseline characteristics are detailed in Table 1.

Table 1. Baseline characteristics by disease subgroup*

Key findings

There were no significant differences in mean baseline HRQoL scores across the disease categories. Additionally, there were no significant differences in mean baseline HRQoL scores between MDS and the other disease categories. Patients with AML with <30% blasts tended to have lower HRQoL scores, but this did not reach statistical significance.

In total, 33% of patients were vulnerable and vulnerability rates were similar across the disease categories. Vulnerable patients with MDS tended to be aged ≥75 years (63%), rated health as poor or fair (65%), and had difficulty with prolonged physical activity (88%; Table 2). Patients who were vulnerable had worse HRQoL scores on all measures except PROMIS Fatigue for MDS/MPN, idiopathic cytopenia of undetermined significance, AML <30%, and at-risk, when pooled over all disease categories and within each disease category. Vulnerable patients with MDS had lower PROMIS Fatigue scores (mean, 56.0; 95% confidence interval [CI], 54.3–57.6) than non-vulnerable patients with MDS (mean 49.5; 95% CI, 48.3–50.7; p < 0.001).

Table 2. Patient characteristics among vulnerable patients*

Excluding FACT-G and PROMIS Fatigue, worse disease prognosis for patients with MDS or MDS/MPN was associated with worse HRQoL scores. Mean EQ-5D-5L scores were 73.4 (95% CI, 70.2–76.5), 72.7 (95% CI, 67.5–77.8), and 64.1 (95% CI, 59.1–69.1) for low-, intermediate-, and high-risk MDS or MDS/MPN, respectively (p = 0.005). Higher risk was associated with worse scores in the QUALMS (p = 0.046), QUALMS-Physical Burden (p = 0.020), and QUALMS-Benefit Finding (p = 0.039). When accounting for vulnerability, higher risk was associated with worse HRQoL scores among non-vulnerable patients with MDS or MDS/MPN for QUALMS-Physical Burden, FACT-G Physical Well-Being, and EQ-5D-5L. However, among vulnerable patients with MDS or MDS/MPN, higher risk was associated with worse HRQoL scores only for QUALMS-Benefit Finding (p = 0.030) and FACT-G Emotional Well-Being (p = 0.036) and not for other HRQoL life measures.

Conclusion

In this study of patients with suspected MDS, HRQoL was not affected by the eventual diagnosis. Among patients who were confirmed to have MDS or MDS/MPN, patients with lower-risk MDS or MDS/MPN had better HRQoL scores. Vulnerability was prevalent in this patient group and was associated with worse HRQoL scores, with the association between risk categories and HRQoL lost among vulnerable patients.

The results from this analysis suggest that baseline bone marrow assessment is needed to diagnose MDS, even among patients who feel well, and that physical function and HRQoL assessment should be performed routinely. Future analyses from this study will assess HRQoL longitudinally.