Universität zu Köln

Theurich, Sebastian ORCID: 0000-0001-5706-8258, Rothschild, Sacha I., Hoffmann, Michael, Fabri, Mario, Sommer, Andrea, Garcia-Marquez, Maria, Thelen, Martin ORCID: 0000-0002-2785-9726, Schill, Catherine, Merki, Ramona, Schmid, Thomas, Koeberle, Dieter, Zippelius, Alfred, Baues, Christian, Mauch, Cornelia, Tigges, Christian, Kreuter, Alexander, Borggrefe, Jan ORCID: 0000-0003-2908-7560, von Bergwelt-Baildon, Michael and Schlaak, Max (2016). Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma. Cancer Immunol. Res., 4 (9). S. 744 - 755. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 2326-6074

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Abstract

Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. (C) 2016 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Theurich, Sebastian UNSPECIFIED orcid.org/0000-0001-5706-8258 UNSPECIFIED Rothschild, Sacha I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fabri, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED Sommer, Andrea UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-Marquez, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, Martin UNSPECIFIED orcid.org/0000-0002-2785-9726 UNSPECIFIED Schill, Catherine UNSPECIFIED UNSPECIFIED UNSPECIFIED Merki, Ramona UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmid, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Koeberle, Dieter UNSPECIFIED UNSPECIFIED UNSPECIFIED Zippelius, Alfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Baues, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mauch, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Tigges, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Kreuter, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Borggrefe, Jan UNSPECIFIED orcid.org/0000-0003-2908-7560 UNSPECIFIED von Bergwelt-Baildon, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlaak, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-262634
DOI:	10.1158/2326-6066.CIR-15-0156
Journal or Publication Title:	Cancer Immunol. Res.
Volume:	4
Number:	9
Page Range:	S. 744 - 755
Date:	2016
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	2326-6074
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RADIATION-THERAPY; SOLID TUMORS; CTLA-4 BLOCKADE; RADIOTHERAPY; IMMUNITY; CELLS; MICROENVIRONMENT; INHIBITION; INCREASES; RESPONSES Multiple languages Oncology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26263