Treatment-related cognitive changes in multiple myeloma: A systematic review and meta-analysis

Multiple myeloma (MM) is an incurable blood cancer with improved survival rates due to advances in treatment, including stem cell transplantation, chemotherapy, and drug therapy. However, cognitive impact of therapies remains unclear. This study aimed to systematically review cognition in patients with MM across treatment pathways and estimate overall effects to determine whether patients experienced cognitive changes after treatment initiation.

A comprehensive search was conducted in PsycINFO, MEDLINE, Embase, and Google Scholar for full-text English articles from 2000 to 2024, aligned with the era of new treatment advances. The review included longitudinal studies and randomized controlled trials (RCTs) on cognition and quality of life in patients with MM treated via three common pathways. Measures included objective tools like the Montreal Cognitive Assessment (MoCA) and self-reported questionnaires like the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30). Two reviewers independently extracted data and assessed study bias. The meta-analyses examined cognitive changes from baseline up to six months from the start of treatment. This duration was identified due to being an intensive phase in MM therapy.

Eighteen studies (N = 5843) were reviewed, and eight (N = 3602) contributed to the meta-analysis. The risk of bias analysis revealed a potential self-selection bias in participant recruitment onto studies, meaning sample populations may not be representative of the MM community. The meta-analysis revealed a significant cognitive decline from baseline across all treatment during the first six months of treatment (standardized mean difference = 1.10, p = .02).

Perceived cognitive decline is prevalent in patients with MM during active treatment (<6 months), but not during the maintenance phase of MM treatment (>6 months). However, findings predominantly rely on self-reported cognitive outcomes, rather than objective assessments, which may limit reliability. More RCTs are needed to investigate domain-specific cognitive impacts using standardized objective measures. In addition, comparisons of cognitive outcomes relative to age/education-matched healthy controls should be made to evaluate cancer-related cognitive impairment.