The role of relative lymphocyte count as a biomarker for the effect of catumaxomab on survival in malignant ascites patients: results from a phase II/III study.
OBJECTIVE
We report the role of relative lymphocyte count (RLC) as a potential biomarker with prognostic impact for catumaxomab efficacy and overall survival (OS) based on a post hoc analysis of the pivotal phase II/III study of intraperitoneal catumaxomab treatment of malignant ascites.


METHODS
The impact of treatment and RLC on OS was evaluated using multivariate Cox models. Kaplan-Meier and log-rank tests were used for group comparisons. Survival analyses were performed on the safety population [patients with paracentesis plus ≥ 1 dose of catumaxomab (n = 157) and paracentesis alone (n = 88)]. Determination of the optimal cutoff value for RLC was based on five optimality criteria.


RESULTS
OS was significantly longer with catumaxomab versus paracentesis alone (P = 0.0219). The 6-month OS rate with catumaxomab was 28.9% versus 6.7% with paracentesis alone. RLC had a positive impact on OS and was an independent prognostic factor (P < 0.0001). In patients with RLC > 13% (n = 159: catumaxomab, 100 and control, 59), catumaxomab was associated with a favorable effect on OS versus paracentesis alone (P = 0.0072), with a median/mean OS benefit of 41/131 days and an increased 6-month survival rate of 37.0% versus 5.2%, respectively. In patients with RLC ≤ 13% at screening (n = 74: catumaxomab, 50 and control, 24), the median (mean) OS difference between the catumaxomab and the control group was 3 (16) days, respectively (P = 0.2561).


CONCLUSIONS
OS was significantly improved after catumaxomab treatment in patients with malignant ascites. An RLC > 13% at baseline was a significant prognostic biomarker.
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom heissm@kliniken-koeln.de.
Markus M
MM
Heiss
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Michael A
MA
Ströhlein
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Carsten
C
Bokemeyer
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Dirk
D
Arnold
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Simon L
SL
Parsons
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Diane
D
Seimetz
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Horst
H
Lindhofer
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Elisabeth
E
Schulze
Authors' Affiliations: Department of Abdominal, Vascular and Transplant Surgery, Cologne-Merheim Medical Center, Witten-Herdecke University, Cologne; University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Neovii (formerly Fresenius) Biotech GmbH; TRION Pharma GmbH, Munich, Germany; and Nottingham University NHS Trust, Nottingham, United Kingdom.
Michael
M
Hennig
D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D001201:Ascites / Q000097:blood* / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D005500:Follow-Up Studies; D006801:Humans; D007274:Injections, Intraperitoneal; D018655:Lymphocyte Count; D009367:Neoplasm Staging; D019152:Paracentesis / Q000401:mortality*; D011379:Prognosis; D015996:Survival Rate
D018033:Antibodies, Bispecific; D015415:Biomarkers; C522419:catumaxomab