Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide-bortezomib combinations

Br J Haematol. 2015 Jun;169(6):843-50. doi: 10.1111/bjh.13382.

Abstract

Proteasome inhibitors (PI) and immunomodulatory agents (IMIDs) have improved the overall survival (OS) of patients with multiple myeloma (MM), but concerns have been raised about increased incidence of extramedullary disease (EMD) after the combined use of PIs and IMIDs for upfront therapy. We evaluated whether the addition of lenalidomide to bortezomib-based front-line regimens precipitated earlier development of EMD. We reviewed the charts of 117 MM patients (median follow-up from diagnosis 6·1 years; range 0·1-10·2 years) enrolled in eight clinical trials of first-line treatment with bortezomib-based regimens, with or without lenalidomide. We assessed development of EMD as extraosseous (distant from bone) or osseous (originating from bone) plasmacytomas. The primary endpoint was time from diagnosis until development of EMD, based on imaging, biopsy and/or physical examination. Any form of EMD at progression was observed in 40 (34·2%) patients, including 21 (18%) osseous, 8 (7%) extraosseous and 11 (9%) both osseous and extraosseous. Median OS was 0·9 years (range 0·1-4·8 years) after extraosseous EMD development. Sensitivity analyses with follow-up times truncated at 5 years detected no statistically significant difference in rates of any EMD form between the two groups (P > 0·2 for each comparison). Therefore, we observed no evidence that bortezomib-lenalidomide-based front-line therapy precipitates earlier EMD.

Keywords: bortezomib; extramedullary disease; extraosseous plasmacytoma; lenalidomide; multiple myeloma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Marrow / pathology
  • Boronic Acids / administration & dosage
  • Bortezomib
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Lenalidomide
  • Male
  • Multiple Myeloma / diagnosis*
  • Multiple Myeloma / epidemiology
  • Multiple Myeloma / etiology*
  • Neoplasm Staging
  • Neoplasms, Second Primary*
  • Plasmacytoma / diagnosis
  • Plasmacytoma / drug therapy
  • Pyrazines / administration & dosage
  • Remission Induction
  • Risk
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • Boronic Acids
  • Pyrazines
  • Thalidomide
  • Bortezomib
  • Lenalidomide