Patient-reported outcomes and skeletal symptoms in multiple myeloma stratified by proteasome inhibitor-based therapy: a prospective interdisciplinary cohort study

Abstract Background Multiple myeloma (MM) frequently causes osteolytic bone disease and skeletal symptoms. Proteasome inhibitors (PIs) are central to MM treatment and in routine practice, PI-based therapy is preferentially selected for patients with more active or symptomatic disease. Hereby, PIs may also exert bone-modulating effects beyond their antimyeloma activity. Whether these biological effects are reflected in patient-reported outcomes or skeletal symptoms during routine care remains unclear. Methods We prospectively enrolled 209 patients with MM during routine interdisciplinary follow-up and stratified them by current PI-based versus non-PI-based treatment status. Sixty-nine patients were reassessed after at least 6 months. Patient-reported outcomes and skeletal symptoms were evaluated using multivariable regression and sensitivity analyses addressing baseline imbalances and treatment selection. Results Seventy-eight patients (37%) were currently receiving PI-based treatment. In adjusted analyses, current PI-based treatment status was not associated with Quality of Life (β = -0.08, 95% CI -0.45 to 0.29; p = 0.662), health-related status (β = -0.06, 95% CI -0.42 to 0.30; p = 0.740), bone pain (OR 0.92, 95% CI 0.48 to 1.74; p = 0.791), or prevalent osteolytic lesions (OR 1.26, 95% CI 0.53 to 2.96; p = 0.601). QoL and health-related status remained comparable during follow-up. MM-related bone pain was numerically more frequent among patients currently receiving PI-based treatment (46% vs. 33%), although the association did not reach statistical significance after multivariable adjustment (OR 1.80, 95% CI 0.93 to 3.48; p = 0.081). Conclusions In this prospective real-world cohort, current PI-based treatment status was not associated with measurable differences in global patient-reported outcomes, overall bone pain, or prevalent osteolytic lesions compared with non-PI-based treatment. MM-related bone pain was numerically more frequent among patients currently receiving PI-based treatment, although the association did not reach statistical significance after multivariable adjustment. These findings provide a real-world description of patient-reported and skeletal outcomes according to current treatment status but do not establish whether the biological effects of proteasome inhibitors on bone remodeling translate into clinically meaningful patient-reported or structural skeletal benefits.