Resumption of bone-modifying agents in relapsed multiple myeloma does not improve outcomes: A real-world analysis

Br J Haematol. 2026 Apr;208(4):1324-1330. doi: 10.1111/bjh.70395. Epub 2026 Feb 24.

Abstract

While bone-modifying agents (BMAs) are well-established components of frontline therapy in multiple myeloma, there are no data in the modern era to support their use in the relapsed setting. We conducted a retrospective analysis of US patients with relapsed/refractory multiple myeloma (RRMM) diagnosed between 2014 and 2023. Progression-free survival (PFS) and overall survival (OS) were analysed using Cox proportional hazards models adjusting for covariates including BMA receipt (BMA-received) versus not (BMA-deferred) at relapse. Of 1112 RRMM patients, 633 (56.9%) patients received BMAs following relapse. Compared to BMA-received patients, BMA-deferred patients had slightly worsened renal function and were less likely to have received BMAs during frontline therapy. There were no differences in PFS between groups: median PFS 10.1 months (95% confidence interval [CI] 8.9-11.8 months) for BMA-deferred patients versus 9.2 months (95% CI 7.7-11.3 months; p = 0.08) for BMA-received patients. There were no differences in OS: median OS 39.6 months (95% CI 33.9-58.1 months) for BMA-deferred patients versus 51.5 months (95% CI 41.8-60.1 months; p = 0.10) for BMA-received patients. Given the lack of clear benefit to BMA in the modern era, our data support future investigations to better personalize decision-making around BMA resumption in RRMM.

Keywords: bone‐modifying agents; denosumab; multiple myeloma; supportive care; zoledronic acid.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Density Conservation Agents* / administration & dosage
  • Bone Density Conservation Agents* / adverse effects
  • Bone Density Conservation Agents* / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / mortality
  • Recurrence
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Bone Density Conservation Agents