¹Medical Center – University of Freiburg, Department of Orthopedics and Trauma Surgery, Freiburg im Breisgau, Deutschland
²Medical Center – University of Freiburg, Department of Medicine, Hematology and Oncology, Freiburg im Breisgau, Deutschland
³Medical Center – University of Freiburg, Clinical Trials Unit, Medical Clinic, Freiburg im Breisgau, Deutschland
⁴Agaplesion Elisabethenstift, Department of Orthopedics and Traumatology, Darmstadt, Deutschland
⁵School of Medicine, University Hospital rechts der Isar, Department of Internal Medicine III, Munich, Deutschland

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Objectives and questions: Multiple myeloma (MM), the second most common haematological malignancy, often follows an indolent course but is unfortunately associated with multiple relapses. Delayed diagnosis of progressive disease (PD) may worsen skeletal symptoms and complications such as skeletal related events (SREs) and can therefore affect quality of life (QoL). This prospective interdisciplinary study aimed to evaluate clinical symptoms and patient-reported outcome measures (PROMs) as warning signs of PD.

Material and methods: A total of 455 MM patients, seen for follow-up visits in our Comprehensive Cancer Center, were included. Skeletal and general symptoms as well as PROMs were assessed, and their associations with serological and radiological findings was evaluated. Differences in PROMs were assessed using Wilcoxon rank-sum test. Odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for sex, immunoglobulin classes and current therapy were calculated using logistic regression models. The study was approved by the local ethics committee. The work was financially supported by Janssen-Cilag GmbH.

Results: PD was observed in 88 (19%) patients. Among these, 58 patients (66%) reported skeletal pain, predominantly located in the spine, and a notable frequency of pain at night. General symptoms occurred in 69 (78%) of patients with PD, with fatigue being the most prevalent symptom. Among all cases of PD, progression was suspected based on clinical symptoms in 59 (67%) patients. In contrast, in 29 (33%) cases, progression was confirmed through serological and/or radiological examination without a prior clinic suspicion. Bone pain at night (OR=3.9, CI: 2.3–6.8, p<0.0001), at various locations (OR=2.7, CI: 1.6–4.7, p=0.0003), and bone pain with known character but at a different site (OR=13.3, CI: 2.8–62.8, p=0.0011) were significantly more frequent in patients with PD than in patients without PD. In addition, general symptoms including weight loss (OR=2.3, CI: 1.3–4.1, p=0.0038) and fatigue (OR=2.8, CI: 1.7–4.7, p<0.0001) were strong predictors of PD. PROMs such as QoL (p<0.0001) and health-related status (p<0.0001), were significantly lower in patients with PD compared to those without PD.

Discussion and conclusions: Physicians should consider PD in MM patients when bone pain at night, pain at various locations or pain with known character but at a different site is reported, particularly when accompanied by general symptoms. Regular collection of PROMs could enhance the diagnosis of PD in routine clinical practice by enabling symptom-based assessments, thereby potentially reducing complications, such as SREs.