title: Relative lymphocyte count is a prognostic parameter in cancer patients with catumaxomab immunotherapy.
abstract: BACKGROUND
  Catumaxomab (anti-EpCAM × anti-CD3) treatment in peritoneal carcinomatosis (PC) of EpCAM-positive cancers was effective in phase I and II studies. Recently, it was approved in the EU for treatment of peritoneal carcinomatosis and malignant ascites. Aim of this hypothesis-generating study was to identify predictive or prognostic biomarkers with relevance for overall survival.
  
  
  METHODS
  34 patients with PC in phase I/II studies with catumaxomab treatment were assessed for age, Karnofsky Index (KI), relative (RLC) and absolute lymphocyte count, relative and absolute granulocyte count, T-cell subsets, NK cells, and monocytes before catumaxomab therapy. Disease control (responder) was defined by stable disease, partial response or complete response (RECIST v1.0) >3 months or survival >6 months. Correlation analysis, Kaplan-Meier curves, ROC calculation, and multivariate regression were used for statistical analysis.
  
  
  RESULTS
  Mean RC values significantly differed between the non-responder (14.0%) and the responder group (23.9%; p=0.001). RLC was correlated with overall survival (p=0.03). RLC of >12% defined by ROC calculation was associated with prolonged survival (p=0.035; hazard ratio of 2.775 for patients with RLC <12%). Patients with RLC >12% showed a mean survival of 15.6 versus 5.6 months in patients with RLC ≥ 12% (p=0.001). Multivariate analysis found the individual RLC before therapy (p=0.039) and the KI performance status (p=0.002) to be independent prognostic parameters. Increasing KI by 1% resulted in a risk decrease of 10.1%. Increasing RLC by 1% resulted in a risk decrease of 4.6%. Age and the extent of PC did not significantly influence survival.
  
  
  CONCLUSIONS
  RLC and KI were identified as potential prognostic parameters for superior disease control and overall survival after catumaxomab treatment. RLC may be used as a biomarker to indicate a suitable immune status for catumaxomab therapy. The predictive impact has to be confirmed in further studies.
authors.affiliation: Department of Abdominal, Vascular and Transplant Surgery, Cologne Merheim Medical Center, Witten/Herdecke University, Ostmerheimer Str. 200, 51109 Cologne, Germany. Electronic address: stroehleinm@kliniken-koeln.de.
authors.forename: Michael Alfred
authors.initials: MA
authors.lastname: Ströhlein
authors.affiliation: Institute for Research in Operative Medicine (IFOM), Witten/Herdecke University, Cologne, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Lefering
authors.affiliation: Department of Abdominal, Vascular and Transplant Surgery, Cologne Merheim Medical Center, Witten/Herdecke University, Ostmerheimer Str. 200, 51109 Cologne, Germany.
authors.forename: Dirk Rolf
authors.initials: DR
authors.lastname: Bulian
authors.affiliation: Department of Abdominal, Vascular and Transplant Surgery, Cologne Merheim Medical Center, Witten/Herdecke University, Ostmerheimer Str. 200, 51109 Cologne, Germany.
authors.forename: Markus Maria
authors.initials: MM
authors.lastname: Heiss
mesh_terms: D000328:Adult; D000368:Aged; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000503:physiopathology / Q000628:therapy*; D011379:Prognosis; D012372:ROC Curve
chemical_list: D018033:Antibodies, Bispecific; C522419:catumaxomab