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*

AML <30%, acute myeloid leukemia with <30% blasts; ANC, absolute neutrophil count; BMI, body mass index; ICUS, idiopathic cytopenia of undetermined significance; IPSS-R, Revised International Prognostic Scoring System; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm; SD, standard deviation; VES-13, Vulnerable Elders Survey. *Adapted from Abel, et al.1 †Vulnerable participants are those with a VES-13 ≥3.
Baseline characteristics, % (unless otherwise specified)	Total (n = 449)	MDS (n = 248)	MDS/MPN (n = 40)	ICUS (n = 48)	AML <30% (n = 15)	At-risk (n = 98)	p-value
Age, mean ± SD	72.1 ± 10.2	71.8 ± 10.1	76.5 ± 7.4	69.9 ± 12.4	73.1 ± 7.8	71.9 ± 10.2	0.039
Gender							0.139
Female	32	35	15	35	27	32	—
Male	68	65	85	65	73	68	—
BMI, mean ± SD	28.8 ± 5.9	29.1 ± 6.3	27.4 ± 5.7	27.8 ± 4.7	30.4 ± 3.2	28.9 ± 5.7	0.257
Blast %, mean ± SD	3.8 ± 6.3	4.1 ± 4.7	3.6 ± 4.5	1.5 ± 4.3	22.2 ± 2.5	1.0 ± 1.1	<0.001
Hemoglobin							<0.001
<8 g/dL	12	17	13	2	7	7	—
8–10 g/dL	30	36	30	21	53	13	—
>10 g/dL	58	47	58	77	40	80	—
Platelets							—
≥50 × 109/L	100	100	100	100	100	100	—
ANC							<0.001
<800 × 106/L	14	18	10	2	80	4	—
≥800 × 106/L	83	80	88	94	20	93	—
Missing	3	2	3	4	0	3	—
Vulnerable†	33	34	45	25	33	31	0.370
IPSS-R
Very low	—	23	13	—	—	—	—
Low	—	29	40	—	—	—	—
Intermediate	—	19	20	—	—	—	—
High	—	11	3	—	—	—	—
Very high	—	12	0	—	—	—	—
Missing	—	7	25	—	—	—	—

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*

AML <30%, acute myeloid leukemia with <30% blasts; ICUS, idiopathic cytopenia of undetermined significance; MDS, myelodysplastic syndrome; MPN, myeloproliferative neoplasm. *Adapted from Abel, et al.1
Characteristics, %	Total (n = 149)	MDS (n = 84)	MDS/MPN (n = 18)	ICUS (n = 12)	AML <30% (n = 5)	At-risk (n = 30)
Age
75–84 years	38	35	61	25	20	43
≥85 years	26	29	22	25	20	23
General health
Health rating of poor or fair	60	65	44	67	80	50
Average difficulty with physical activities
Any activity	90	88	100	83	100	90
Walking quarter mile	73	74	83	50	100	70
Heavy housework	71	68	83	67	100	70
Stooping, crouching, or kneeling	60	58	72	33	80	63
Lifting objects ≥10 lbs	33	33	17	33	60	37
Reaching or extending arms above shoulder	23	25	0	33	40	27
Writing or grasping small objects	11	12	0	0	40	13
Walking across room	0	0	0	0	0	0
Doing light housework	0	0	0	0	0	0
Difficulty/require assistance with activities due to health
Any activity	42	42	33	42	40	50
Shopping	34	33	17	33	40	43
Managing money	17	15	22	33	0	17
Bathing or showering	15	18	11	0	0	17

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.