title: Circulating activin-A is elevated in patients with advanced multiple myeloma and correlates with extensive bone involvement and inferior survival; no alterations post-lenalidomide and dexamethasone therapy.
abstract: BACKGROUND
  Activin-A is a transforming growth factor -β superfamily member, which seems to be implicated in the biology of osteolytic disease in multiple myeloma.
  
  
  METHODS
  Circulating activin-A was evaluated in 98 newly diagnosed myeloma patients (85 with symptomatic disease), in 40 patients with relapsed myeloma before and after four cycles of lenalidomide and dexamethasone (RD), in 27 healthy controls and in 10 monoclonal gammopathy of undetermined significance patients.
  
  
  RESULTS
  Patients with newly diagnosed symptomatic myeloma had increased circulating activin-A compared with controls (P < 0.001), while patients with relapsed disease had elevated activin-A even compared with symptomatic patients at diagnosis (P < 0.001). High activin-A correlated with advanced International Staging System stage (P = 0.002), increased bone resorption (P < 0.001) and extensive bone disease (P = 0.03). Low levels of activin-A (<442 pg/ml) were associated with superior median overall survival: not reached versus 59 months (P = 0.04), while activin-A inversely correlated with survival as a continuous variable (P < 0.001). RD did not alter circulating activin-A after four cycles of treatment, even in responders.
  
  
  CONCLUSIONS
  High circulating activin-A correlates with advanced features of myeloma, supporting the rationale for the use of activin-A antagonists, such as sotatercept in myeloma. The inability of RD to reduce activin-A reveals RD as a good candidate for combination therapies with activin-A antagonists in myeloma.
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece. Electronic address: eterpos@med.uoa.gr.
authors.forename: E
authors.initials: E
authors.lastname: Terpos
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Kastritis
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: D
authors.initials: D
authors.lastname: Christoulas
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: M
authors.initials: M
authors.lastname: Gkotzamanidou
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Eleutherakis-Papaiakovou
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Kanellias
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Papatheodorou
authors.affiliation: Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.
authors.forename: M A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D028341:Activins / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001842:Bone and Bones / Q000473:pathology*; D016022:Case-Control Studies; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; C422405:activin A; D028341:Activins; D013792:Thalidomide; D003907:Dexamethasone; D000077269:Lenalidomide