Prediagnostic opioid use and survival in multiple myeloma: a nationwide register-based study

Multiple myeloma (MM) accounts for approximately 1% of incident cancers worldwide and carries substantial mortality. Diagnostic delay is common, with more than one-third of patients requiring emergency care at diagnosis, a presentation linked to inferior prognosis. Pain is a frequent early MM symptom, yet the extent and prognostic relevance of prediagnostic opioid use remains poorly characterized. Using nationwide Danish registers, we conducted a matched case-control analysis of prediagnostic opioid use, irrespective of indication, and its association with overall survival (OS) among MM patients. The study included 6,953 MM patients diagnosed in 2001-2021 and 101,793 matched population controls. Compared with controls, opioid use was first elevated among MM cases approximately 2.25 years before diagnosis, increasing more consistently closer to diagnosis. High prediagnostic opioid use (≥ 10 mg daily oral morphine equivalents) was associated with shorter OS, compared with no opioid use (1-year OS 72% vs. 82%; adjusted hazard ratio 1.23, 95% CI 1.07-1.41). These findings indicate that opioid use increases closer to MM diagnosis date, likely reflecting pain related to undiagnosed MM. Furthermore, prediagnostic opioid use was associated with shorter OS independently of available prognostic factors, including ISS stage and myeloma bone disease.