Grip strength predicts overall survival of patients with myelodysplastic syndrome in a multivariable model

Abstract Background: Myelodysplastic syndrome (MDS) is a clonal hematologic disorder characterized by cytopenias and a risk of progression to leukemia. Frailty, a state of reduced physiologic reserve, is prevalent among older individuals and is common in patients with MDS. MDS specific frailty scores such as the FS-15 can refine existing prognostic disease models. Physical function markers such as grip strength are frequently used to assess physical performance as a marker of frailty. In other cancer populations, grip strength predicts disease-specific mortality and cardiovascular disease. However, a paucity of data exists on the relationship between markers of physical performance and MDS outcomes, particularly when other disease markers and functional evaluations are considered. The aim of the present study was to determine the value of physical function testing in predicting the survival of patients with MDS. Methods: We conducted a retrospective cohort analysis of patients prospectively enrolled in the MDS-CAN registry (NCT02537990). The MDS-CAN registry (2006 to present) includes patients ≥ 18 years old with a diagnosis of MDS, MDS/MPN, or low blast count AML (20-30%). Grip strength, 10 x sit-stand test, and 4 meter walk test were collected as markers of physical performance. Grip strength was measured with a handheld dynamometer and was calculated as the average of three readings of the patient's dominant hand, stratified by sex. Survival analysis was performed by Kaplan-Meier analysis. Multivariable logistic regression models for overall survival were developed with backwards elimination. Results: A total of 1372 patients were included in the study, with a mean age at enrollment of 73.46 (SD 10.04) years. Most (896/1372; 65.31%) were male, while 529 (38.56%) received treatment with a hypomethylating agent. At a median follow-up of 2.8 years, 831 patients (60.57%) had died. 1022 patients had available grip strength data. Stratified by quartile, actuarial median overall survival (OS) (95% CI) was 23.6 months (19.1–27.9) for the lowest 25%, 28.2 months (22.4–39.9) for the 25th to 50th percentile, 38.9 months (29.2–47.1) for the 50th to 75th percentile, and 45 months (32.8-56.2) for the highest 25%. Reduced grip strength at baseline was associated with worse overall survival (Log-rank test p<.0001). These significant differences in overall survival were observed in longer term follow-up with 5-year OS of 39.3% (34.8-44.3%) in patients with grip strength above the median compared to 27.5% (23.1-32.7%) in patients with grip strength below the median. A 4 meter walk test faster than the median was associated with an actuarial median OS of 41.27 months (34.0-48.7), exceeding patients slower than median with actuarial median OS of 25.79 (23.0-30.2). A Stand-Sit test time below the median was associated with significantly higher actuarial median OS at 44.8 months (36.8-56.6) compared to 32.6 (25.9-37.6) months. Multivariable analysis included patient and disease-specific factors significant in univariate analysis. Grip strength measured at baseline below the median value retained an independent significant effect on OS measured from time of enrollment in multivariable analysis (HR 1.37 [1.11-1.69]). This multivariable analysis included the FS-15 assessment of frailty with HR 2.58 [1.93-3.43]) for scores of 0.26-0.6 vs. 0-0.25, HR 4.55 [2.40-8.65] for scores of 0.61-1.0 vs. 0-0.25, and HR 2.60 [1.54-4.37] for scores of 0.61-1.0 vs. 0.26-0.6. Other factors significant in multivariable analysis were QLQ-C30 Fatigue score below median (HR 0.75 [0.60-0.94]), higher ferritin (HR 1.13 [1.03-1.24]), IPSS-R (High Vs Low: HR 3.88 [3.01-5.00] Int vs low: HR 2.02 [1.55-2.65] High vs Int: HR 1.92 [1.48-2.48]), and MDS-Comorbidity index(HR 1.52 [1.22-1.9] for 1-2 vs 0 and HR 1.71 [1.18-2.48] for 3+ vs 0). Conclusion: Our study provides evidence that grip strength, an easy to obtain measure of physical functioning, predicts survival in MDS patients. We again validate the important prognostic impact of patient reported outcomes and patient-related factors that refine the prognosis of IPSS-R. Further research is warranted in assessing the impact of grip strength on treatment responses and tolerability in a longitudinal analysis.