title: Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents.
abstract: BACKGROUND
  High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is considered the standard of care for multiple myeloma (MM) patients <65 years. Safety and outcome of ASCT for patients >65 years is currently uncertain, especially since the introduction of novel agents for induction and maintenance therapy. Furthermore, there are no conclusive data available on risk assessment in elderly patients treated with HDT.
  
  
  METHODS
  We retrospectively analyzed 202 patients ≥60 years with newly diagnosed MM who underwent ASCT at our institution. Patients were stratified by age into three groups (60-64, 65-69 and 70-75 years). For safety assessment, we compared data about hospitalization, hematopoetic reconstitution and early mortality. Remission before and after ASCT was analyzed according to age and application of novel agents. Event-free (EFS) and overall survival (OS) were analyzed to identify impact of age, remission before/after ASCT and maintenance therapy as well as ISS score and cytogenetic aberrations on outcome in elderly patients.
  
  
  RESULTS
  The assessment of safety, remission before/after ASCT as well as EFS and OS showed no significant differences between the three groups (median EFS: 60-64 years: 27 months; 65-69 years: 23 months; 70-75 years: 23 months; median OS: not reached). Patients receiving novel agents as part of induction therapy achieved significantly higher nCR + CR rates than patients treated without novel agents. In Cox regression analysis, ISS and cytogenetics as well as remission after ASCT had the highest prognostic impact on EFS and OS. Maintenance therapy was associated with longer EFS in uni- and multivariate analyses.
  
  
  CONCLUSIONS
  ASCT is feasible for selected patients >65 and >70 years without increased mortality. Age at transplantation has no prognostic significance on outcome after ASCT. Novel agents during induction therapy and maintenance therapy improves outcome of older patients eligible for ASCT. ISS and cytogenetic analysis should be carried out routinely for risk assessment.
authors.affiliation: Department of Medicine V, University Hospital of Heidelberg, Heidelberg.
authors.forename: M
authors.initials: M
authors.lastname: Merz
authors.forename: K
authors.initials: K
authors.lastname: Neben
authors.forename: M S
authors.initials: MS
authors.lastname: Raab
authors.forename: S
authors.initials: S
authors.lastname: Sauer
authors.forename: G
authors.initials: G
authors.lastname: Egerer
authors.forename: M
authors.initials: M
authors.lastname: Hundemer
authors.forename: D
authors.initials: D
authors.lastname: Hose
authors.forename: C
authors.initials: C
authors.lastname: Kunz
authors.forename: C
authors.initials: C
authors.lastname: Heiß
authors.forename: A D
authors.initials: AD
authors.lastname: Ho
authors.forename: H
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: J
authors.initials: J
authors.lastname: Hillengass
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D064592:Autografts; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D006801:Humans; D060828:Induction Chemotherapy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
chemical_list: D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide
keywords: autologous stem cell transplantation; elderly; high-dose therapy; maintenance therapy; multiple myeloma; novel agents