title: Combined treatment of metastatic breast cancer (MBC) by high-dose chemotherapy (HDCT) and bispecific antibodies: a pilot study.
abstract: This pilot study analyzed the efficacy and toxicity of high-dose chemotherapy (HDCT), autologous stem-cell transplantation (ASCT) and subsequent immunotherapy with T-cell reinfusion and trifunctional antibodies (trAbs) in chemotherapy-sensitive patients with metastatic breast cancer (MBC).
  
  
  METHODS
  After leukapheresis and cryopreservation of T-cells, patients received 2 cycles of induction chemotherapy ET (epirubicin/paclitaxel) and 1 cycle of El (epirubicin/ifosfamide), followed by G-CSF and stem-cell harvest. After a final cycle of ET, responders (CR/PR) underwent HDCT (thiotepa 600 mg/m2/melphalan 140-180 mg/m2) and ASCT. Once reconstitution was achieved, T-cells were reinfused, followed by application of trifunctional antibodies with specificities anti-EpCAM X anti-CD3 and anti-Her2/neu X anti-CD3.
  
  
  RESULTS
  Thirty-three patients were recruited into the study and 19, who had responded to initial chemotherapy, underwent HDCT and ASCT (4 CR, 15 PR, OR = 57.6%; 95% CI: 40-75%). Two early deaths were observed (1 toxic, 1 early progression). T-cell reinfusion and trAbs were given to 17 patients. TrAbs treatment resulted in intermittent fever, chills and elevated liver enzymes, which were seen in all patients. The median overall survival was 27.7 months (range: 5.9-82.6+). Patients who received 3 trAbs doses showed a trend towards an improved overall survival (47.2 vs. 22.4 months, p = 0.08 log rank).
  
  
  CONCLUSIONS
  This pilot study has shown the feasibility of combining HDCT with immunotherapy in MBC. Further investigation of this approach is indicated.
authors.affiliation: Department of Hematology-Oncology, University of Munich, Germany. Joachim.Stemmler@med.uni-muenchen.de
authors.forename: H J
authors.initials: HJ
authors.lastname: Stemmler
authors.forename: C
authors.initials: C
authors.lastname: Salat
authors.forename: H
authors.initials: H
authors.lastname: Lindhofer
authors.forename: H
authors.initials: H
authors.lastname: Menzel
authors.forename: M
authors.initials: M
authors.lastname: Untch
authors.forename: S
authors.initials: S
authors.lastname: Kahlert
authors.forename: G
authors.initials: G
authors.lastname: Konecny
authors.forename: H
authors.initials: H
authors.lastname: Sauer
authors.forename: G
authors.initials: G
authors.lastname: Ledderose
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
authors.forename: H J
authors.initials: HJ
authors.lastname: Kolb
mesh_terms: D000328:Adult; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001781:Blood Component Removal; D001943:Breast Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000628:therapy*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D007116:Immunization, Passive / Q000379:methods; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive / Q000379:methods; D008213:Lymphocyte Activation; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010865:Pilot Projects; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000276:immunology; D013852:Thiotepa / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D018033:Antibodies, Bispecific; D016179:Granulocyte Colony-Stimulating Factor; D015251:Epirubicin; D013852:Thiotepa; D017239:Paclitaxel; D008558:Melphalan; D007069:Ifosfamide