title: Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide-bortezomib combinations.
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.
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Varga
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Wanling
authors.initials: W
authors.lastname: Xie
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Laubach
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Ghobrial
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Elizabeth K
authors.initials: EK
authors.lastname: O'Donnell
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Weinstock
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Paba-Prada
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Warren
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Maglio
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schlossman
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Nikhil C
authors.initials: NC
authors.lastname: Munshi
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Noopur
authors.initials: N
authors.lastname: Raje
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Edie
authors.initials: E
authors.lastname: Weller
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
authors.affiliation: Dana Farber Cancer Institute, Harvard Medical School, Jerome Lipper Multiple Myeloma Center, Boston, MA, USA.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D000077269:Lenalidomide; D008297:Male; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000453:epidemiology / Q000209:etiology*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary; D010954:Plasmacytoma / Q000175:diagnosis / Q000188:drug therapy; D011719:Pyrazines / Q000008:administration & dosage; D012074:Remission Induction; D012306:Risk; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D000077269:Lenalidomide
keywords: bortezomib; extramedullary disease; extraosseous plasmacytoma; lenalidomide; multiple myeloma