Landscape Assessment of the Perceptions of Distress and Symptom Burden in Patients with Monoclonal Gammopathy of Unknown Significance (MGUS) and Smoldering Multiple Myeloma (SMM)

Background: Multiple myeloma (MM) is a fatal plasma cell malignancy that is proceeded by the asymptomatic precursor conditions of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). These conditions have been historically considered benign, and thus the standard clinical paradigm consists of watchful waiting until progression to clinically symptomatic MM - a paradigm that is anecdotally reported as a source of distress in this patient population. Despite well-documented evidence that patients with MM experience substantial emotional distress and symptom burden,(1) little is known about psychological distress and symptom burden in the setting of MGUS and SMM.

Methods: We conducted a cross-sectional analysis of patients with MGUS and SMM participating in a longitudinal study of plasma cell precursor disease. Between February and May 2024, patients with MGUS and SMM were offered the opportunity to complete validated questionnaires to assess anxiety (Hospital Anxiety and Depression Scale (HADS)), depression (HADS), post-traumatic stress disorder (PTSD) (PTSD Checklist Civilian Version (PCL-C)), symptom burden (Edmonton Symptom Assessment System Revised (ESAS-r)) and fatigue (Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)). We used histograms and Q-Q plots to check for normality and the Mann-Whitney U test to detect unadjusted associations between sociodemographic factors and each subscale. Quantile regression was used in adjusted models to estimate the median scores for each subscale conditional on age, sex, and income.

Results: A total of 423 adults with MGUS (n=228) and SMM (n=195) completed the study questionnaires. The mean age was 64.9 years (range: 32 to 88 years), 40.7% were male, and nearly 90% were White, non-Hispanic. The prevalence of clinically significant anxiety, depression, PTSD symptoms, symptom burden, and fatigue was 27%, 13%, 24%, 29%, and 20% respectively. Mean subscale scores for aspects of psychological distress and symptom burden were not significantly different between MGUS and SMM patients.

Overall, there were statistically significant differences between sociodemographic factors and the perceptions of psychological distress, symptom burden, and fatigue. In adjusted models, those with lower income had higher levels of depression (p<0.02), PTSD (p<0.05), symptom burden (p<0.02), and fatigue (p<0.02). Females had higher anxiety (p=0.01), and marginally higher symptom burden (p=0.05) compared to males. Older age was associated with lower anxiety (p<0.001), lower PTSD (p=0.03), lower symptom burden (p<0.001), and higher fatigue (p=0.02). Race, ethnicity, and education level were not associated with any subscale in adjusted models.

Conclusions: Patients with MGUS and SMM experience substantial psychological distress prior to developing MM. Certain sociodemographic subgroups of patients had higher rates of psychological distress, symptom burden and fatigue for reasons that remain to be elucidated. It is essential that we develop a more comprehensive understanding of the supportive care needs of patients to improve their quality of life and care throughout their illness course.

1. O'Donnell EK, Shapiro YN, Yee AJ, Nadeem O, Hu BY, Laubach JP, et al. Quality of life, psychological distress, and prognostic perceptions in patients with multiple myeloma. Cancer. 2022;128(10):1996-2004.

O'Donnell:BMS: Consultancy; Legend Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Exact Sciences: Honoraria; Natera: Membership on an entity's Board of Directors or advisory committees; Grail: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy, Honoraria. Nadeem:JNJ: Research Funding; Pfizer: Honoraria; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; GPCR Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees. El-Jawahri:Incyte: Consultancy; Tuesday Health: Consultancy; Novartis: Consultancy; GSK: Consultancy. Ghobrial:AbbVie: Consultancy; GlaxoSmithKline: Consultancy; 10X Genomics: Consultancy; Oncopeptides: Consultancy; CurioScience: Consultancy, Other: Speaker fees; Bristol Myers Squibb: Consultancy, Other: Speaker fees; Standard Biotools: Other: Speaker fees; Sognef: Consultancy; Regeneron: Consultancy, Other: Speaker fees; Aptitude Health: Consultancy; Binding Site, part of Thermo Fisher Scientific: Consultancy; Sanofi: Consultancy; Disc Medicine: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Other: Speaker fees; PreDICTA Bioscience: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Other: Co-founder; Amgen: Consultancy, Other: Speaker fees; Novartis: Consultancy; Huron Consulting: Consultancy; Takeda: Consultancy, Other: Speaker fees; Menarini Silicon Biosystems: Consultancy, Other: Speaker fees; Vor Biopharma: Other: Speaker fees; Pfizer: Consultancy, Other: Speaker fees; Adaptive: Consultancy; Window Therapeutics: Consultancy. Marinac:Natera: Membership on an entity's Board of Directors or advisory committees; Exact Sciences: Membership on an entity's Board of Directors or advisory committees.