Physical and Psychological Factors Influencing Fatigue and Quality of Life in Multiple Myeloma Survivors: Preliminary Results from the Mascot Lifestyle Study
Authors: Heinrich Malgorzata , Land Joanne , McCourt Orla , Philpott Stephanie , Paton Bruce , Beeken Rebecca J , Smith Lee , De-Silva Dunnya , Rismani Ali , D'Sa Shirley , Chew Anastasia , Mehta Atul , Fisher Abigail , Hackshaw Allan , Yong Kwee L 
Published: October 2019

Abstract
Background. With increasingly effective treatments, patients with Multiple Myeloma ('MM') are living longer, but burden of disease and cumulative toxicities of therapy impair quality of life ('QoL') and well-being. Fatigue and bone pain frequently persist long after treatment, and during disease stability. Research in solid cancers indicates that patients who are more physically active have reduced symptom burden, less fatigue and improved QoL. Less work has been done in MM, partly due to the older and frailer patient group, and the high prevalence of osteolytic bone disease and fracture risk. The MASCOT survivorship study aims to explore the main determinants of fatigue and QoL in patients who have completed chemotherapy, with particular emphasis on bone pain, physical fitness and strength.
Methods. Multivariable linear regressions were performed between: 1) fatigue and measures of physical health and fitness and 2) each of 6 measures of QoL as outcome variables (fatigue, emotional well-being, functional well-being, global well-being, EQ5D QoL, and overall health status) with each of pain, depression and anxiety; all adjusted for age, sex, time since treatment, Hb, fat body %, fat trunk %, BMI, VO2peak, left grip strength, right grip strength, left leg muscle strength, right leg muscle strength, and muscle mass. Results are shown as regression coefficients B (change in fatigue score for 1 unit increase in physical health or fitness; or a change in QoL for 1 unit increase in pain, depression or anxiety).
80 patients aged 36-78 years (male, n=46), were studied at median 13.5 months (range 2-161) since last treatment. Physical health and cardiovascular fitness were assessed using objective measures: % body and trunk adiposity, muscle mass, body mass index (TANITA scales), VO2peak (CPET on a cycle ergometer), leg muscle strength and grip strength. The presence of bone pain was self-reported and evaluated in a clinical consultation. Standardised questionnaires were used to assess mood (HADS), fatigue (FACIT), functional and emotional well-being (FACT-G) and health related QoL (EQ5D). Higher scores on FACT-G and FACIT, health status scales and lower scores on HADS and EQ5D indicated better quality of life.
Results. We investigated the influence of physical fitness on levels of fatigue, using multivariable regression. We found that higher levels of fatigue were associated with higher BMI (B = -1.28, CI =-2.28 to -0.28, p=0.013) and greater left leg muscle strength (B=0.16, CI=0.003 to 0.32, p=0.046) were linked to lower levels of fatigue independent of sex, age, time since treatment, pain and all other indicators of physical fitness.
We observed that pain was associated with more fatigue (B = -6.80, CI = -11.45 to -2.15, p=0.005), decreased well-being (emotional: B = -1.92, CI =-3.50 to -0.35, p=0.018; global: B = -2.55, CI -4.59 to -0.51, p=0.015), decreased health related QoL (B =1.34, CI=0.42 to 2.26, p=0.005) and worse depression (B = 1.37, CI=-0.01 to 2.74, p=0.05), even when adjusting for sex, age, time since treatment and physical health and fitness.
Depression was found to be an independent predictor of QoL with higher depression scores associated with greater fatigue (B = -2.52, CI=-3.09 to -1.96,p=<0.001), decreased emotional (B=-0.52, CI=-0.77 to -0.26, p<0.001), functional (B=-1.39, CI=-1.88 to -0.90, p<0.001) and global well-being (B=-0.96, CI=-1.24 to -0.67, p=<0.001), decreased health related QoL (B=0.30, CI=0.15 to 0.45, p<0.001) and health status (B= -3.07, CI=-4.36 to -1.78, p<0.001), and higher levels of anxiety (B=0.81, CI=0.54 to 1.08, p<0.001). Higher anxiety was also associated with greater fatigue, decreased emotional, functional, and global well-being, decreased health related QoL and health status, with similar strength of correlations to those found between depression and QoL.
Conclusions. Our findings confirm the important contribution of physical fitness to fatigue and QoL in these patients. Regardless of physical fitness status, however, the presence of pain and impaired psychological health remain independent drivers of fatigue and diminished QoL. Research involving exercise programmes designed to improve physical strength and fitness combined with effective pain management and psychological support are needed to provide the evidence base for much needed rehabilitative interventions.

Disclosures
Yong: Autolus Ltd: Equity Ownership, Patents & Royalties: APRIL based chimeric antigen receptor; Janssen: Research Funding.