Editors
John B.A.G. Haanen
Iwona Lugowska
Marina Chiara Garassino
Raffaele Califano
Contributors
1.1 Immune Checkpoints
Mahjoubi L. Gustave Roussy, Université Paris-Saclay, Département d’Innovation Thérapeutique et d’Essais Précoces, Villejuif, France
Rizvi N.A. Thoracic Oncology, Columbia University, New York, NY, USA
Marabelle A. INSERM U1015, Gustave Roussy, Villejuif, France
1.2 Adoptive T Cell Therapy
I. M. Svane Center for Cancer Immune Therapy-CCIT, Department of Haematology and Oncology, Herlev Hospital, University of Copenhagen, Denmark
M. Donia Center for Cancer Immune Therapy-CCIT, Department of Haematology and Oncology, Herlev Hospital, University of Copenhagen, Denmark
Ö. Met Center for Cancer Immune Therapy-CCIT, Department of Haematology and Oncology, Herlev Hospital, University of Copenhagen, Denmark
1.3 Vaccines
C. J. M. Melief Leiden University Medical Center, ISA Pharmaceuticals, Netherlands
R. Zappasodi Ludwig Collaborative and Swim Across America Laboratory, Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY, USA
M. C. Garassino Medical Thoracic Oncology Unit, Department of Medical Oncology and Hematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
M. Di Nicola Medical Thoracic Oncology Unit, Department of Medical Oncology and Hematology, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
1.4 Biomarkers for Immunotherapy
J. R. Gosney Department of Cellular Pathology, Royal Liverpool University Hospital and Institute of Translational Medicine, University of Liverpool, Liverpool, UK
A. Haragan Department of Cellular Pathology, Royal Liverpool University Hospital and Institute of Translational Medicine, University of Liverpool, Liverpool, UK
G. M. Laing Department of Pathology, Aberdeen University Medical School, Aberdeen, Royal Infirmary, Foresterhill, UK
K. M. Kerr Department of Pathology, Aberdeen University Medical School, Aberdeen, Royal Infirmary, Foresterhill, UK
1.5 Resistance to Immunotherapy
S. Sangaletti Molecular Immunology Unit, Research Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
C. Chiodoni Molecular Immunology Unit, Research Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
M. P. Colombo Molecular Immunology Unit, Research Department, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
Section 2: Immunotherapies in specific disease groups – State of the art
2.1 Melanoma
R. Teixeira de Sousa Department of Medical Oncology, Hospital de Santa Maria, Lisbon, Portugal / Department of Medical Oncology, Hospital Lusíadas, Lisbon, Portugal
A. Mansinho Department of Medical Oncology, Hospital de Santa Maria, Lisbon, Portugal
P. Lorigan Department of Medical Oncology, University of Manchester and Christie NHS Foundation Trust, Manchester, UK
2.2 Merkel Cell Carcinoma
S. Bhatia Department of Medicine/Medical Oncology, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA
J. Becker Department of Dermatology, University Hospital Essen, Essen, Germany / Translational Skin Cancer Research (TSCR), German Cancer Consortium (DKTK), Essen, Germany
2.3.1 Non-small Cell Lung Cancer
S. Peters Oncology Department, Lausanne University Hospital, Lausanne, Switzerland
S. Zimmermann Oncology Department, Lausanne University Hospital, Lausanne, Switzerland
2.3.2 Small Cell Lung Cancer
R. Tay Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK
A. RossiDepartment of Medical Oncology, Scientific Institute for Research and Health, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
R. Califano Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, UK / Department of Medical Oncology, Manchester University NHS Foundation Trust, Manchester; Division of Cancer Sciences, The University of Manchester, Manchester, UK
2.3.3 Mesothelioma
P. Baas Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
M. J. Disselhorst Department of Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands
2.3.4 Other Thoracic Malignancies
N. Girard Institut du Thorax Curie-Montsouris, Institut Curie, Institut Mutualiste Montsouris, Paris, France
C. Merveilleux du Vignaux Université de Lyon, Université Claude Bernard Lyon 1, Lyon, France
2.4.1 Renal Cancer
L. Albiges Gustave Roussy, Université Paris-Saclay, Department of Cancer Medecine, Villejuif, France
M. Strijbos Medical Oncology Department, Algemeen Ziekenhuis Klina, Antwerp, Belgium
A. Rodriguez-Vida Medical Oncology Department, Hospital del Mar, Barcelona, Spain
B. Escudier Gustave Roussy, Université Paris-Saclay, Department of Cancer Medecine, Villejuif, France
2.4.2 Bladder Cancer
A. Necchi Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
V. Crolley Barts Cancer Centre, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
T. Powles Barts Cancer Centre, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
2.5.1 Microsatellite Instability-high
L. Aulakh Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA / Swim Across America Laboratory at Johns Hopkins, Baltimore, MD, USA / Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA / Ludwig Center and Howard Hughes Medical Institute at Johns Hopkins, Baltimore, MD, USA
D. T. Le Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA / Swim Across America Laboratory at Johns Hopkins, Baltimore, MD, USA / Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
M. V. Karamouzis Molecular Oncology Unit, Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece / First Department of Internal Medicine, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
G. Argilés Vall d’Hebrón Institut of Oncology (VHIO), Barcelona, Spain / Vall d’Hebrón University Hospital, Barcelona, Spain
J. Tabernero Vall d’Hebrón Institut of Oncology (VHIO), Barcelona, Spain / Vall d’Hebrón University Hospital, Barcelona, Spain
2.5.2 Gastric and Oesophageal Malignancies
D. Arnold Instituto CUF de Oncologia (I.C.O.), Lisbon, Portugal
E. Smyth Cambridge University Hospitals, Cambridge, UK
2.5.3 Hepatocellular Carcinoma
J. J. Harding Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell School of Medicine, New York, NY, USA
T. Watanabe Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
I. El-Dika Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell School of Medicine, New York, NY, USA
N. Nishida Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
G. K. Abou-Alfa Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell School of Medicine, New York, NY, USA
M. Kudo Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
2.6 Immunotherapy in Head and Neck Tumours (HPV+ and HPV-)
S. Alfieri Head and Neck Cancer Medical Oncology 3 Department, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy
M. V. Karamouzis Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece / First Department of Internal Medicine, Laiko Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece
S. Cavalieri Head and Neck Cancer Medical Oncology 3 Department, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy
L. Licitra Head and Neck Cancer Medical Oncology 3 Department, Fondazione IRCCS, Istituto Nazionale dei Tumori (INT), Milan, Italy / University of Milan, Milan, Italy
2.7 Immunotherapies in Lymphoma
V. Ballová Haematology/Oncology, Kantonsspital Baden, Baden, Switzerland
M. Ghielmini Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona, Switzerland
2.8 Gynaecological Malignancies
J. Stewart Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK
S. Banerjee Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, UK
D. Lorusso Gynecologic Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
E. Tripodi Gynecologic Oncology Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy
Section 3: Implications for clinical practice
3.1 Management of Adverse Events Related to Immune Checkpoint Blockade
C. Boutros Department of Medicine, Gustave Roussy, Villejuif, France
F. Carbonnel AP-HP, Department of Gastroenterology, University Hospital of Bicêtre, Paris Sud University, Le Kremlin-Bicêtre, France / Paris Sud University, Le Kremlin Bicêtre, France
C. Robert Department of Medicine, Gustave Roussy, Villejuif, France / Paris Sud University, Le Kremlin Bicêtre, France / INSERM Unit U981, Villejuif, France
3.2 Immune Checkpoint Blockade: Response Patterns and Assessment of Response
M. Jalving Department of Medical Oncology, University Medical Centre, Groningen, Netherlands
E. G. E. de Vries Department of Medical Oncology, University Medical Centre, Groningen, Netherlands
L. Seymour Canadian Cancer Trials Group, Queens University, Kingston, Ontario, Canada
3.3 Immunotherapy in Special Populations
L. Spain Skin Unit, The Royal Marsden NHS Foundation Trust, London, UK
J. Larkin Skin Unit, The Royal Marsden NHS Foundation Trust, London, UK
A. M. Menzies Melanoma Institute Australia and The University of Sydney, Sydney, Australia / Royal North Shore and Mater Hospitals, Sydney, Australia
3.4 Cancer Immunotherapy Trials: Challenges and Opportunities
P. Nathan Mount Vernon Cancer Centre, Northwood, UK
3.5 Future Perspectives
J. S. Weber Laura and Isaac Perlmutter Cancer Center, NYU Langone Health System, New York, NY, USA
Declarations of Interest
1.1 Immune Checkpoints
- Dr Mahjoubi has reported no conflicts of interest.
- Dr Rizvi is an investigator and co-investigator of industry-sponsored clinical trials using immune checkpoint-targeted drugs. He has provided consulting services and has participated in scientific advisory boards of companies developing immune checkpoint-targeted therapies. He has served as a consultant to AstraZeneca, Lilly, Roche/Genentech, Pfizer, Novartis, Bristol-Myers Squibb and Merck Sharp & Dohme. He is a shareholder in Gritstone Oncology.
- Dr Marabelle is an investigator and co-investigator of industry-sponsored clinical trials using immune checkpoint-targeted drugs. He has provided consulting services and has participated in scientific advisory boards of companies developing immune checkpoint-targeted therapies. He has received consultancy fees and honoraria from AstraZeneca, Merck Serono, Roche/Genentech, Pfizer, Novartis, Lytix Pharma, Bristol-Myers Squibb and Merck Sharp & Dohme. He has no stock ownership.
1.2 Adoptive T Cell Therapy
- Dr Svane has reported honoraria/consultation fees for Roche, Novartis, Merck, Merck Sharp & Dohme, Celgene, Incyte, Pfizer, Bristol-Myers Squibb, AstraZeneca, TILTh Bio and IO Biotech. Dr Svane is a co-founder of IO Biotech.
- Dr Donia has reported no potential conflict of interest.
- Dr Met has reported no potential conflict of interest.
1.3 Vaccines
- Dr Melief is Chief Scientific Officer of ISA Pharmaceuticals, a biotech company developing synthetic long peptide vaccines. As such he receives a salary and participates in a management participation plan.
- Dr Zappasodi has reported no potential conflicts of interest.
- Dr Garassino has declared grants/supports from Merck Sharp & Dohme and Eli Lilly; advisory board/consultancy for: Inivata, Merck Sharp & Dohme, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Roche, AstraZeneca, Novartis, Celgene, MedImmune, Pfizer, Takeda and Ignyta.
- Dr Di Nicola has reported no potential conflicts of interest.
1.4 Biomarkers for Immunotherapy
- Dr Gosney is a paid advisor to and speaker for Abbvie, Agilent, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Diaceutics, Lilly & Co, Merck Sharp & Dohme, Novartis, Pfizer and Roche.
- Dr Haragan has reported no potential conflicts of interest.
- Dr Laing has reported no potential conflicts of interest.
- Dr Kerr is a paid advisor to and speaker for Abbvie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly & Co, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer, Roche and Roche Diagnostics.
1.5 Resistance to Immunotherapy
- Dr Sangaletti has reported no potential conflicts of interest.
- Dr Chiodoni has reported no potential conflicts of interest.
- Dr Colombo has reported no potential conflicts of interest.
Section 2: Immunotherapies in specific disease groups – State of the art
2.1 Melanoma
- Dr Teixeira de Sousa has been a consultant/advisor/paid speaker for Roche, Merck Sharp & Dohme, Novartis and Bristol-Myers Squibb.
- Dr Mansinho has reported no potential conflicts of interest.
- Dr Lorigan has been a consultant/advisor/paid speaker for Merck Sharp & Dohme, Bristol-Myers Squibb, Novartis, Amgen, GlaxoSmithKline, Nektar, Roche and Neracare, and received support for travel from Merck Sharp & Dohme and Bristol-Myers Squibb.
2.2 Merkel Cell Carcinoma
- Dr Bhatia has received advisory board honoraria from Genentech and EMD-Serono; his institution (University of Washington) has received research funding from EMD-Serono, Merck, Bristol-Myers Squibb, Oncosec and Immune Design.
- Professor Becker has received speaker honoraria from Amgen, Merck Serono and Pfizer; he has received advisory board honoraria from Amgen, CureVac, eTheRNA, Lytix, Merck Serono, Novartis, Rigontec and Takeda; and he has received research funding from Boehringer Ingelheim, Bristol-Myers Squibb and Merck Serono. Professor Becker’s activities with Bristol-Myers Squibb, Merck Serono and Pfizer are related to the submitted report (therapy of advanced MCC).
2.3.1 Non-small Cell Lung Cancer
- Professor Peters has reported no conflicts of interest.
- Dr Zimmermann has reported no conflicts of interest.
2.3.2 Small Cell Lung Cancer
- Dr Tay has reported no potential conflicts of interest.
- Dr Rossi has reported no potential conflicts of interest.
- Dr Califano has reported no potential conflicts of interest.
2.3.3 Mesothelioma
- Dr Baas has received research grants from or has served as a consultant for Merck and Bristol-Myers Squibb.
- Dr Disselhorst has reported no potential conflicts of interest.
2.3.4 Other Thoracic Malignancies
- Dr Girard has reported consultancy from AstraZeneca, Bristol-Myers Squibb, Hoffman-La Roche, Merck Sharp & Dohme and Pfizer.
- Dr Merveilleux du Vignaux has reported no potential conflicts of interest.
2.4.1 Renal Cancer
- Dr Albiges has declared advisory / consulting roles for Novartis, Pfizer, Sanofi, Amgen, Bristol-Myers Squibb, Ipsen, Roche and Astellas.
- Dr Strijbos has declared advisory / consulting roles for Novartis, Bristol-Myers Squibb, Sanofi and Janssen Pharmaceuticals; research grants from Janssen Pharmaceuticals.
- Dr Rodriguez-Vida has declared advisory / consulting roles for Novartis, Pfizer, Sanofi, Bristol-Myers Squibb, Roche, Astellas, Janssen and Bayer.
- Dr Escudier has declared advisory / consulting roles for Bayer, Novartis, Pfizer, Exelixis, Bristol-Myers Squibb, Ipsen and EUSA pharma; honoraria from Pfizer, Novartis, Bayer, Bristol-Myers Squibb, Ipsen, Exelixis and Roche/Genentech.
2.4.2 Bladder Cancer
- Dr Necchi has reported no potential conflicts of interest.
- Dr Crolley has reported no potential conflicts of interest.
- Dr Powles has reported no potential conflicts of interest.
2.5.1 Microsatellite Instability-high
- Dr Aulakh has reported no potential conflicts of interest.
- Dr Le has declared research funding and advisory board honoraria for Bristol-Myers Squibb, and research funding, advisory board and speaking honoraria for Merck.
- Dr Karamouzis has reported no potential conflicts of interest.
- Dr Argilés has reported no potential conflicts of interest.
- Dr Tabernero has declared participation in advisory boards of Bayer, Boehringer Ingelheim, Genentech/Roche, Lilly, Merck Sharp & Dohme, Merck Serono, Novartis, Roche, Sanofi, Symphogen and Taiho.
2.5.2 Gastric and Oesophageal Malignancies
- Dr Arnold has reported consulting and advisory services, speaking or writing engagements, and public presentations for Roche, Merck Serono, Bayer Healthcare, Servier, BTG, Terumo, Sanofi Oncology and Eli Lilly.
- Dr Smyth has received honoraria for an advisory role from Five Prime Therapeutics, Bristol-Myers Squibb, Gritstone Oncology and Servier.
2.5.3 Hepatocellular Carcinoma
- Dr Harding has received research funding and has consulted for AstraZeneca and Bristol-Myers Squibb.
- Dr Watanabe has reported no potential conflicts of interest.
- Dr El-Dika has reported no potential conflicts of interest.
- Dr Nishida has reported no potential conflicts of interest.
- Dr Abou-Alfa has received research funding and has consulted for AstraZeneca and Bristol-Myers Squibb.
- Dr Kudo has received research funding from Bristol-Myers Squibb.
2.6 Immunotherapy in Head and Neck Tumours (HPV+ and HPV-)
- Dr Alfieri has reported no potential conflicts of interest.
- Dr Karamouzis has reported no potential conflicts of interest.
- Dr Cavalieri has reported no potential conflicts of interest.
- Dr Licitra has reported research grants/support from Eisai, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Novartis, AstraZeneca and Roche (funds received by the author’s institution for clinical studies and research activities in which she is involved); honoraria or consultation fees from Eisai, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck Serono, Boehringer Ingelheim, Novartis, AstraZeneca, Roche, Bayer, Debiopharm and SOBI; and travel grants from Merck Serono, Bristol-Myers Squibb, Merck Sharp & Dohme, Debiopharm, SOBI and Bayer.
2.7 Immunotherapies in Lymphoma
- Dr Ballova has reported no potential conflicts of interest.
- Professor Ghielmini has reported receiving honoraria from Roche, Celgene, Mundipharma, Janssen, Abbvie, Bayer and Gilead.
2.8 Gynaecological Malignancies
- Dr Stewart has reported no potential conflicts of interest.
- Dr Banerjee has reported no potential conflicts of interest; she has participated as an investigator in immunotherapy trials (Merck Sharp & Dohme, Roche, Tesaro and Pfizer).
- Dr Lorusso has reported no potential conflicts of interest.
- Dr Tripodi has reported no potential conflicts of interest.
Section 3: Implications for clinical practice
3.1 Management of Adverse Events Related to Immune Checkpoint Blockade
- Dr Boutros has declared consultancy for Bristol-Myers Squibb.
- Dr Carbonnel has declared consultancy for Abbvie (lecture), Bristol-Myers Squibb (lecture and board), Enterome (board), Janssen (board), Mayoly Spindler (research grant and lecture), Merck Sharp & Dohme (lecture and board), Pfizer (lecture and board) and Takeda (lecture). Additional disclosures more than 2 years old: consultancy for Falk, Ferring (travel grant and board), Genentech (board), Hospira (lecture), Otsuka (board) and Vifor (board).
- Caroline Robert has declared consultancy for Roche, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Merck and Pierre Fabre.
3.2 Immune Checkpoint Blockade: Response Patterns and Assessment of Response
- Dr Jalving has participated in an advisory panel for Merck, payment made available to UMCG.
- Dr de Vries has received grant/research support from Amgen, Roche/Genentech, Chugai Pharma, AstraZeneca and CytomX, all payments made available to the UMCG.
- Dr Seymour has reported no potential conflicts of interest.
3.3 Immunotherapy in Special Populations
- Dr Spain has reported no potential conflicts of interest.
- Dr Larkin receives institutional research support from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis and Pfizer; is a consultant for Eisai, Bristol-Myers Squibb, Merck Sharp & Dohme, GlaxoSmithKline, Kymab, Pfizer, Novartis, Roche/Genentech, Secarna, Pierre-Fabre and EUSA Pharma; and receives support from NIHR RM/ICR Biomedical Research Centre for Cancer.
- Dr Menzies has participated in advisory boards for Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche and Pierre-Fabre.
3.4 Cancer Immunotherapy Trials: Challenges and Opportunities
- Dr Nathan has participated in advisory boards for AstraZeneca, Bristol-Myers Squibb, Ipsen, Merck, Merck Sharp & Dohme, Novartis and Pfizer.
3.5 Future Perspectives
- Dr Weber has stock or other ownership in Altor BioScience, Celldex and CytomX Therapeutics; received honoraria from Bristol-Myers Squibb, Merck, Genentech, AbbVie, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Eisai, Altor BioScience, Lion Biotechnologies, Amgen, Roche, Ichor Medical Systems, Celldex, cCam Biotherapeutics, Pieris Pharmaceuticals, CytomX Therapeutics, Nektar, Novartis and Medivation; has had a consulting or advisory role with Celldex, Ichor Medical Systems, cCam Biotherapeutics, Lion Biotechnologies, Pieris Pharmaceuticals, Altor BioScience, Bristol-Myers Squibb, Merck, Genentech, Roche, Amgen, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, AbbVie, Eisai, CytomX Therapeutics, Nektar, Novartis and Medivation; received research funding (Institute) from Bristol-Myers Squibb, Merck, Glaxo-SmithKline, Genentech, Astellas Pharma, Incyte, Roche and Novartis; and received travel and accommodation expenses from Bristol-Myers Squibb, GlaxoSmithKline, Daiichi Sankyo, Pieris Pharmaceuticals, cCam Biotherapeutics, Lion Biotechnologies, Roche, Celldex, Amgen, Merck, AstraZeneca, Genentech and Novartis.
