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:
CreatorsEmailORCIDORCID Put Code
Theurich, SebastianUNSPECIFIEDorcid.org/0000-0001-5706-8258UNSPECIFIED
Rothschild, Sacha I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fabri, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sommer, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Marquez, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, MartinUNSPECIFIEDorcid.org/0000-0002-2785-9726UNSPECIFIED
Schill, CatherineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merki, RamonaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmid, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koeberle, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zippelius, AlfredUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baues, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mauch, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tigges, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreuter, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borggrefe, JanUNSPECIFIEDorcid.org/0000-0003-2908-7560UNSPECIFIED
von Bergwelt-Baildon, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schlaak, MaxUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
RADIATION-THERAPY; SOLID TUMORS; CTLA-4 BLOCKADE; RADIOTHERAPY; IMMUNITY; CELLS; MICROENVIRONMENT; INHIBITION; INCREASES; RESPONSESMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26263

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