Combined low-dose ipilimumab and pembrolizumab after sequential ipilimumab and pembrolizumab failure in advanced melanoma |
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| Institution: | 1. Department of Dermatology, University Hospital Erlangen, Erlangen, Germany;2. Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany;1. Melanoma Institute Australia, Sydney, NSW, Australia;2. The University of Sydney, Sydney, NSW, Australia;3. Liz Plummer Cancer Centre, Cairns, Qld, Australia;4. Royal North Shore Hospital, Sydney, NSW, Australia;5. Royal Prince Alfred Hospital, Camperdown, NSW, Australia;6. Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia;7. Macquarie University, North Ryde, NSW, Australia;8. Westmead Millennium Institute for Medical Research, Westmead, NSW, Australia;9. School of Medicine, University of Western Sydney, NSW, Australia;1. Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain;2. MRC Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit and University of Edinburgh Cancer Research UK Centre, Western General Hospital, EH4 2XR Edinburgh, UK;1. Laser and Skin Surgery Center of New York, New York, New York;2. The Ronald O. Perelman Department of Dermatology, New York University, New York, New York;3. Michelson Diagnostics Ltd, Maidstone, United Kingdom;1. Skin Cancer Center Hannover, Dept. of Dermatology and Allergy, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany;2. Department of Dermatology, Helios Clinic, Erfurt, Germany;3. Department of Dermatology, Quedlinburg, Germany;4. Department of Dermatology, University of Lübeck, Lübeck, Germany;5. Department of Dermatology, Saarland University Medical School, Homburg, Germany;6. Skin Cancer Unit, German Cancer Research Center (DKFZ) and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany;7. Department of Dermatology, Venereology, and Allergology, HELIOS St. Elisabeth Hospital Oberhausen, University Witten-Herdecke, Germany;8. Department of Dermatology, Elbe Clinic, Buxtehude, Germany;9. Department of Dermatology, Ludwigshafen Hospital, Ludwigshafen, Germany;10. Department of Dermatology, University of Duisburg-Essen, Essen, Germany;1. University of Siena and Center for Immuno-Oncology, Department of Oncology, University Hospital, Siena, Italy;2. Department of Medicine, Melanoma Institute Australia, The University of Sydney, Westmead and Blacktown Hospitals, Corner Hawkesbury Road and Darcy Road, Sydney, NSW 2145, Australia;3. Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent''s Hospital, 370 Victoria Street, Sydney, NSW 2010, Australia;4. Department of Oncology, Division of Medical Oncology, Juravinski Cancer Centre, McMaster University, 699 Concession Street, Hamilton, ON L8V 5C2, Canada;5. Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, 100 Medical Plaza Driveway #550, Los Angeles, CA 90095, USA;6. Unit of Melanoma, Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Via Mariano Semmola, Naples 80131, Italy;7. Departments of Oncology and Medicine, Lady Davis Institute for Medical Research, Jewish General Hospital, and McGill University, 3755 Cote Ste-Catherine Road, Montreal, QC H3T 1E2, Canada;8. Department of Medical Oncology Unit of Melanoma Medical Oncology, Department of Cancer Centre, University of Toronto, 610 University Avenue, Toronto, ON M5G 2M9, Canada;9. Department of Experimental Oncology, Istituto Europeo di Oncologia – IRCCS, Via Ripamonti 435, Milan 20141, Italy;10. Central West Cancer Care Centre, Orange, NSW, Australia;11. Western Sydney University, 1530 Forest Road, Orange, NSW 2800, Australia;12. Unit of Melanoma Medical Oncology, Department of Medical Oncology and Hematology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, Milan 20133, Italy;13. Gobal Drug Development, Oncology, Novartis, One Health Plaza, East Hanover, NJ 07936, USA;14. Department of Clinical Oncology, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;15. Department of Hematology/Oncology, The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, 11800 Wilshire Boulevard, Suite 300, Los Angeles, CA 90025, USA;1. Department of Dermatology, AP-HP, Hôpital Saint-Louis, Paris, France;2. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland;3. Department of Dermatology, Bordeaux, France;4. Department of Dermatology, Le Mans, France;5. Centre de Recherche en Cancérologie de Lyon, Institut de Cancérologie des Hospices Civils de Lyon, Université de Lyon, Lyon, France;6. Department of Dermatology, Université Paul Sabatier, Institut Universitaire du Cancer de Toulouse-Oncopole et CHU Larrey, Toulouse, France;7. Biostatistics, AP-HP, Hôtel-Dieu Hospital, Paris, France;8. Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland;9. APHP Dermatology, Department of Dermatology and CIC, Paris 7 Diderot University, INSERM U976, Hôpital Saint-Louis, Paris, France |
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| Abstract: | With the wide use of anti-PD-1 therapy, an increasing number of patients progress under treatment. Combined immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies induces higher response rates as first-line treatment in comparison to single-agent therapy, however, with substantial toxicity since the combination of ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) induced 55% grade 3/4 treatment-related adverse events and treatment discontinuation rates of 39%. In this case series, we investigated the efficacy and toxicity of the combined immunotherapy with low-dose ipilimumab (1 mg/kg) plus pembrolizumab (2 mg/kg) in patients with metastatic melanoma with progressive disease under sequential monotherapy with both agents. All patients had received at least three lines of treatment, 78% of patients were M1c, and 67% had brain metastases. Stable disease was observed in 3 out of 9 patients with a median overall survival of 8 months after double checkpoint inhibition. No treatment-related grade 3/4 adverse events occurred, and none of the patients needed to discontinue the treatment due to toxicity. Further trials are needed to investigate combined immunotherapy as rescue treatment in heavily pretreated melanoma patients to find optimal dosage in regard to outcome and toxicity. |
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| Keywords: | Ipilimumab Pembrolizumab Anti-PD-1 Melanoma Combined immunotherapy |
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