The Impact of Weight Loss Grading Scale, a Measure of Cancer Cachexia, on Clinical Outcomes in Patients with Acute Myeloid Leukemia
Authors: Jabir Abdur Rahman , Ciarrocca Anna Lisa , O'Connell Nathaniel , Needles Kelly , Pardee Timothy S , Bhave Rupali , Ellis Leslie R , Wieduwilt Matthew J. , Powell Bayard L , Burkart Madelyn 
Published: December 2024

Introduction:
Cancer cachexia is characterized by a metabolic shift towards whole-body catabolism, progressive muscle loss and functional impairment. CT-based measures for cachexia, sarcopenia and adipopenia, were found to be significant negative prognostic factors for overall survival (OS) in patients with acute myeloid leukemia (AML). There remains no set protocol to accurately identify patients at risk for cachexia or to incorporate it into current risk stratification. Current CT-based measures are costly, burdensome and not routinely performed for AML work-up. The body mass index (BMI)-adjusted weight loss grading scale (WLGS) has emerged as a classification criterion for cancer associated weight loss, considering only BMI and percentage of weight lost at a certain time point. This study examines the relationship between cachexia as measured by the WLGS and survival outcomes in AML patients.
Methods:
This is a retrospective study of adult patients (≥18 years old) treated for AML (non-APL) at Atrium Health Wake Forest Baptist Medical Center between 1/1/2015 to 12/1/2023. The WLGS is graded on a scale of 0-4; a score of 0 indicates no cachexia and a score of 4 indicates severe cachexia. WLGS was obtained 1, 3 and 12 months post induction therapy. Kaplan-Meier Survival curves were calculated to determine time to death and time to relapse. Hazard ratios using multivariable cox proportional hazard models (adjusted for AML diagnosis, AML risk category per ELN 2022 risk classification, ECOG status, age, neighborhood deprivation measured by area deprivation index, and Charlson Comorbidity Index) were calculated to determine differences in survival based on WLGS scores at 3 months. A multivariable linear mixed model (LMM) was used to model mean WLGS score over time by AML risk category via an interaction effect, adjusted for the same variables as the Cox models.
Results
565 patients were included; 61% male, 39% female and median age of 67 years. Overall 67% had de novo AML, 28% had secondary AML, and 4% had therapy-related AML; 5% had favorable disease, 23% had intermediate disease and 52% had adverse disease. Risk was unknown in 113 patients. Patients received 7+3 (43%), vyxeos (9%), 7+3+ targeted agent (5%), HMA + venetoclax (30%), HMA alone (6%) or other (6%) as frontline therapy. Higher WLGS, defined as a score ≥ 3, composed 31% and 19% of patients at 3 and 12 months post induction therapy, respectively. Patients with a high WLGS at 3 months had a significantly shorter survival; median time to death was 25.7 months in patients with low WLGS≤ 2 compared to 16.4 months in patients with high WLGS (Log Rank Test; p-value = 0.001). From the adjusted Cox model, patients who lived to 3 months with 3-month data available (N=452), patients with a WLGS ≥ 3 at 3 months were found to have a 36% increased risk of death relative to patients with lower WLGS (HR = 1.36, 95% CI = [1.06, 1.74]). The association between WLGS and time to relapse was non-significant (Log-Rank Test; p-value = 0.60). From the LMM for mean WLGS score over time, WLGS scores were similar across each risk category 1 month post induction (favorable 1.33; intermediate 1.43; adverse 1.26). However, patients with intermediate and adverse risk disease had significantly higher (p&lt;0.05) WLGS scores at 3 and 12 months (mean scores: 1.70 and 1.91 at 3 months; 1.61 and 1.83 at 12 months respectively) compared to patients with favorable disease (mean score: 0.99 at 3 months and 0.83 at 12 months).
Conclusion
Our study found cachexia as measured by WLGS is associated with mortality outcomes in AML. Specifically, patients with a higher WLGS score at 3 months have a significantly increased risk of death and a shorter survival. However, there was no impact on time to relapse. Patients with intermediate and adverse risk disease have higher WLGS scores at 3 and 12 months post induction therapy, suggesting these patients are at a higher risk of developing cachexia compared to patients with favorable disease. Both weight and BMI are easily obtainable making the WLGS a cost-effective alternative to measure cachexia. Therefore, the WLGS could be a potential tool to assess for cachexia and improve risk stratification in AML, especially when considering a patient for transplant or treatment for more adverse disease. Future studies are needed to determine if the incorporation of cachexia-based treatment, specifically for higher risk disease, could potentially improve treatment tolerance and survival.