Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients
Background Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of ni...
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2020-05-01
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| author | Carola Berking Jessica C Hassel Lisa Zimmer Ralf Gutzmer Teresa Amaral Thomas Eigentler Claus Garbe Julia Tietze Thilo Gambichler Patrick Terheyden Felix Kiecker Sarah Schaefer Henner Stege Katharina Kaehler Sebastian Haferkamp Jochen Uttikal David Rafei-Shamsabadi Lydia Reinhardt Friedegund Meier Ante Karoglan Christian Posch Claudia Pfoehler Kai Thoms Dirk Debus Rudolf Herbst Steffen Emmert Carmen Loquai Frank Meiss Thomas Tueting Vanessa Heinrich |
| author_facet | Carola Berking Jessica C Hassel Lisa Zimmer Ralf Gutzmer Teresa Amaral Thomas Eigentler Claus Garbe Julia Tietze Thilo Gambichler Patrick Terheyden Felix Kiecker Sarah Schaefer Henner Stege Katharina Kaehler Sebastian Haferkamp Jochen Uttikal David Rafei-Shamsabadi Lydia Reinhardt Friedegund Meier Ante Karoglan Christian Posch Claudia Pfoehler Kai Thoms Dirk Debus Rudolf Herbst Steffen Emmert Carmen Loquai Frank Meiss Thomas Tueting Vanessa Heinrich |
| author_sort | Carola Berking |
| collection | DOAJ |
| description | Background Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.Methods Patients with MBM treated with nivolumab plus ipilimumab in 23 German Skin Cancer Centers between April 2015 and October 2018 were investigated. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS.Results Three hundred and eighty patients were included in this study and 31% had symptomatic MBM (60/193 with data available) at the time of start nivolumab plus ipilimumab. The median follow-up was 18 months and the 2 years and 3 years OS rates were 41% and 30%, respectively. We identified the following independently significant prognostic factors for OS: elevated serum lactate dehydrogenase and protein S100B levels, number of MBM and Eastern Cooperative Oncology Group performance status. In these patients treated with checkpoint inhibition first-line or later, in the subgroup of patients with BRAFV600-mutated melanoma we found no differences in terms of OS when receiving first-line either BRAF and MEK inhibitors or nivolumab plus ipilimumab (p=0.085). In BRAF wild-type patients treated with nivolumab plus ipilimumab in first-line or later there was also no difference in OS (p=0.996). Local therapy with stereotactic radiosurgery or surgery led to an improvement in OS compared with not receiving local therapy (p=0.009), regardless of the timepoint of the local therapy. Receiving combined immunotherapy for MBM in first-line or at a later time point made no difference in terms of OS in this study population (p=0.119).Conclusion Immunotherapy with nivolumab plus ipilimumab, particularly in combination with stereotactic radiosurgery or surgery improves OS in asymptomatic and symptomatic MBM. |
| format | Article |
| id | doaj-art-1da3310c8b1b40ca8b61e76efd7b29f5 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2020-05-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-1da3310c8b1b40ca8b61e76efd7b29f52024-11-09T13:05:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000333Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patientsCarola Berking0Jessica C Hassel1Lisa Zimmer2Ralf Gutzmer3Teresa Amaral4Thomas Eigentler5Claus Garbe6Julia Tietze7Thilo Gambichler8Patrick Terheyden9Felix Kiecker10Sarah Schaefer11Henner Stege12Katharina Kaehler13Sebastian Haferkamp14Jochen Uttikal15David Rafei-Shamsabadi16Lydia Reinhardt17Friedegund Meier18Ante Karoglan19Christian Posch20Claudia Pfoehler21Kai Thoms22Dirk Debus23Rudolf Herbst24Steffen Emmert25Carmen Loquai26Frank Meiss27Thomas Tueting28Vanessa Heinrich29Deutsches Zentrum Immuntherapie (DZI), Erlangen, GermanyUniversity Hospital Heidelberg, Heidelberg, GermanyDepartment of Dermatology, Venerology and Allergology, University Hospital Essen and German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Essen, GermanyDepartment of Dermatology, Muelenkreiskliniken Minden and Ruhr University Bochum, Minden, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyCharité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Berlin, GermanyDepartment of Dermatology, University Hospital Tübingen, Eberhard Karls University of Tübingen, Tübingen, GermanyAff1 grid.30389.310000 0001 2348 0690DermatologyUniversity of Califonia Davis, Sacramento CA USADepartment of Dermatology, Ruhr-University Bochum, Bochum, GermanyDepartment of Dermatology, Allergology and Venerology, University Medical Center Schleswig Holstein Lübeck Campus, Lubeck, GermanyDepartment of Dermatology, Vivantes Hospital Neukölln, Berlin, Germany3 Skin Cancer Center, Department of Dermatology and National Center for Tumor Diseases (NCT), University Hospital Heidelberg, Heidelberg, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany5 Skin Cancer Center, Department of Dermatology, University Hospital Kiel, Kiel, GermanyDepartment of Dermatology, University Hospital Regensburg, Regensburg, Germany10 Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany14 Skin Cancer Center, Department of Dermatology and Venerology, Medical Centre University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, GermanyDepartment of Dermatology, University Hospital Carl Gustav Carus, Dresden, GermanySkin Cancer Center at the University Cancer Centre Dresden and National Center for Tumor Diseases Dresden, Dresden, Germany16 Department of Dermatology, University Hospital Magdeburg, Magdeburg, GermanyTechnical University of Munich, German Cancer Consortium (DKTK), Munich, Germany5University Medical School of Saarland, Department of Dermatology, Homburg, Germany21 Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Dermatology, Nuremberg Hospital, Nurnberg, GermanyDepartment of Dermatology, HELIOS Hospital Erfurt, Erfurt, Germany25 Clinic for Dermatology and Venereology, University Medical Center, Rostock, GermanyDepartment of Dermatology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, GermanyDepartment of Dermatology and Venerology, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany16 Department of Dermatology, University Hospital Magdeburg, Magdeburg, Germany26 Clinic of Radiation Oncology, Eberhard Karls University of Tuebingen, Tuebingen, GermanyBackground Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.Methods Patients with MBM treated with nivolumab plus ipilimumab in 23 German Skin Cancer Centers between April 2015 and October 2018 were investigated. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS.Results Three hundred and eighty patients were included in this study and 31% had symptomatic MBM (60/193 with data available) at the time of start nivolumab plus ipilimumab. The median follow-up was 18 months and the 2 years and 3 years OS rates were 41% and 30%, respectively. We identified the following independently significant prognostic factors for OS: elevated serum lactate dehydrogenase and protein S100B levels, number of MBM and Eastern Cooperative Oncology Group performance status. In these patients treated with checkpoint inhibition first-line or later, in the subgroup of patients with BRAFV600-mutated melanoma we found no differences in terms of OS when receiving first-line either BRAF and MEK inhibitors or nivolumab plus ipilimumab (p=0.085). In BRAF wild-type patients treated with nivolumab plus ipilimumab in first-line or later there was also no difference in OS (p=0.996). Local therapy with stereotactic radiosurgery or surgery led to an improvement in OS compared with not receiving local therapy (p=0.009), regardless of the timepoint of the local therapy. Receiving combined immunotherapy for MBM in first-line or at a later time point made no difference in terms of OS in this study population (p=0.119).Conclusion Immunotherapy with nivolumab plus ipilimumab, particularly in combination with stereotactic radiosurgery or surgery improves OS in asymptomatic and symptomatic MBM.https://jitc.bmj.com/content/8/1/e000333.full |
| spellingShingle | Carola Berking Jessica C Hassel Lisa Zimmer Ralf Gutzmer Teresa Amaral Thomas Eigentler Claus Garbe Julia Tietze Thilo Gambichler Patrick Terheyden Felix Kiecker Sarah Schaefer Henner Stege Katharina Kaehler Sebastian Haferkamp Jochen Uttikal David Rafei-Shamsabadi Lydia Reinhardt Friedegund Meier Ante Karoglan Christian Posch Claudia Pfoehler Kai Thoms Dirk Debus Rudolf Herbst Steffen Emmert Carmen Loquai Frank Meiss Thomas Tueting Vanessa Heinrich Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients Journal for ImmunoTherapy of Cancer |
| title | Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients |
| title_full | Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients |
| title_fullStr | Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients |
| title_full_unstemmed | Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients |
| title_short | Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients |
| title_sort | combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis a decog study in 380 patients |
| url | https://jitc.bmj.com/content/8/1/e000333.full |
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