Charles Dolladille1, Stéphane Ederhy2, Marion Sassier3, Jennifer Cautela4,5,6,7,8, Franck Thuny4,5,6,7,8, Ariel A Cohen2, Sophie Fedrizzi3, Basile Chrétien3, Angélique Da-Silva3,9, Anne-Flore Plane10, Damien Legallois11, Paul U Milliez11, Véronique Lelong-Boulouard3, Joachim Alexandre1. 1. Normandie University, University of Caen Normandy, Centre Hospitalier Universitaire (CHU) de Caen Normandie, PICARO Cardio-oncology Program, Department of Pharmacology, EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, Caen, France. 2. Hôpitaux Universitaires Paris-Est, Assistance Publique-Hôpitaux de Paris, Hôpital Saint Antoine, Service de Cardiologie, Unico, Unité de Cardio-Oncologie APHP.6, GRC Groupe de Recherche Clinique en Cardio Oncologie, Inserm 856, Université Pierre et Marie Curie, Paris, France. 3. CHU de Caen Normandie, Department of Pharmacology, Caen, France. 4. Aix-Marseille Mediterranean University, Assistance Publique-Hôpitaux de Marseille, Marseille, France. 5. Cardio-Oncology Center, Unit of Heart Failure and Valvular Heart Diseases, Department of Cardiology, Hôpital Nord, Marseille, France. 6. Centre de Recherche Cardiovasculaire et Nutrition, Inserm 1263, Inra, Marseille, France. 7. Groupe Méditerranéen de Cardio-Oncologie, Marseille, France. 8. Oncosafety Network of the Early Phases Cancer Trials Center, Marseille, France. 9. Centre Francois Baclesse Centre de Lutte Contre le Cancer (Cancer Centre), Caen, France. 10. CHU de Caen Normandie, PICARO Cardio-oncology Program, Department of Cardiology, Caen, France. 11. Normandie University, UNICAEN, CHU de Caen Normandie, PICARO Cardio-oncology Program, Department of Cardiology, EA 4650, Signalisation, Électrophysiologie et Imagerie des Lésions d'Ischémie-Reperfusion Myocardique, Caen, France.
Abstract
Importance: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE). Objective: To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences. Design, Setting, and Participants: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included. Main Outcomes and Measures: The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge. Results: A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs. Conclusions and Relevance: This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.
Importance: Limited information is available on the safety of a rechallenge with an immune checkpoint inhibitor (ICI) after an immune-related adverse event (irAE). Objective: To identify the recurrence rate of the same irAE that prompted discontinuation of ICI therapy after an ICI rechallenge in patients with cancer and to identify the clinical features associated with such recurrences. Design, Setting, and Participants: This observational, cross-sectional, pharmacovigilance cohort study examined individual case safety reports from the World Health Organization database VigiBase, which contains case reports from more than 130 countries. Case reports were extracted from database inception (1967) to September 1, 2019. All consecutive ICI cases with at least 1 associated irAE were included. Main Outcomes and Measures: The primary outcome was the rate of recurrence of the initial irAE after an ICI rechallenge. Secondary outcomes included the factors associated with the recurrence after a rechallenge among informative rechallenges, the recurrence rate according to the ICI regimen (anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy, anti-cytotoxic T-lymphocyte antigen-4 monotherapy, or combination therapy), and the rate of occurrence of a different irAE after a rechallenge. Results: A total of 24 079 irAE cases associated with at least 1 ICI were identified. Among the irAEs, 452 of 6123 irAEs associated with ICI rechallenges (7.4%) were informative rechallenges. One hundred thirty recurrences (28.8%; 95% CI, 24.8-33.1) of the initial irAE were observed. In a rechallenge, colitis (reporting odds ratio [OR], 1.77; 95% CI, 1.14-2.75; P = .01), hepatitis (reporting OR, 3.38; 95% CI, 1.31-8.74; P = .01), and pneumonitis (reporting OR, 2.26; 95% CI, 1.18-4.32; P = .01) were associated with a higher recurrence rate, whereas adrenal events were associated with a lower recurrence rate (reporting OR, 0.33; 95% CI, 0.13-0.86; P = .03) compared with other irAEs. Conclusions and Relevance: This cohort study found a 28.8% recurrence rate of the same irAE associated with the discontinuation of ICI therapy after a rechallenge with the same ICI. Resuming ICI therapy could be considered for select patients, with appropriate monitoring and use of standard treatment algorithms to identify and treat toxic effects.
Authors: Michael A Postow; Jason Chesney; Anna C Pavlick; Caroline Robert; Kenneth Grossmann; David McDermott; Gerald P Linette; Nicolas Meyer; Jeffrey K Giguere; Sanjiv S Agarwala; Montaser Shaheen; Marc S Ernstoff; David Minor; April K Salama; Matthew Taylor; Patrick A Ott; Linda M Rollin; Christine Horak; Paul Gagnier; Jedd D Wolchok; F Stephen Hodi Journal: N Engl J Med Date: 2015-04-20 Impact factor: 91.245
Authors: M H Pollack; A Betof; H Dearden; K Rapazzo; I Valentine; A S Brohl; K K Ancell; G V Long; A M Menzies; Z Eroglu; D B Johnson; A N Shoushtari Journal: Ann Oncol Date: 2018-01-01 Impact factor: 32.976
Authors: Robert J Motzer; Nizar M Tannir; David F McDermott; Osvaldo Arén Frontera; Bohuslav Melichar; Toni K Choueiri; Elizabeth R Plimack; Philippe Barthélémy; Camillo Porta; Saby George; Thomas Powles; Frede Donskov; Victoria Neiman; Christian K Kollmannsberger; Pamela Salman; Howard Gurney; Robert Hawkins; Alain Ravaud; Marc-Oliver Grimm; Sergio Bracarda; Carlos H Barrios; Yoshihiko Tomita; Daniel Castellano; Brian I Rini; Allen C Chen; Sabeen Mekan; M Brent McHenry; Megan Wind-Rotolo; Justin Doan; Padmanee Sharma; Hans J Hammers; Bernard Escudier Journal: N Engl J Med Date: 2018-03-21 Impact factor: 91.245
Authors: Scott J Antonia; José A López-Martin; Johanna Bendell; Patrick A Ott; Matthew Taylor; Joseph Paul Eder; Dirk Jäger; M Catherine Pietanza; Dung T Le; Filippo de Braud; Michael A Morse; Paolo A Ascierto; Leora Horn; Asim Amin; Rathi N Pillai; Jeffry Evans; Ian Chau; Petri Bono; Akin Atmaca; Padmanee Sharma; Christopher T Harbison; Chen-Sheng Lin; Olaf Christensen; Emiliano Calvo Journal: Lancet Oncol Date: 2016-06-04 Impact factor: 41.316
Authors: A M Menzies; D B Johnson; S Ramanujam; V G Atkinson; A N M Wong; J J Park; J L McQuade; A N Shoushtari; K K Tsai; Z Eroglu; O Klein; J C Hassel; J A Sosman; A Guminski; R J Sullivan; A Ribas; M S Carlino; M A Davies; S K Sandhu; G V Long Journal: Ann Oncol Date: 2017-02-01 Impact factor: 32.976
Authors: Daniel Y Wang; Joe-Elie Salem; Justine V Cohen; Sunandana Chandra; Christian Menzer; Fei Ye; Shilin Zhao; Satya Das; Kathryn E Beckermann; Lisa Ha; W Kimryn Rathmell; Kristin K Ancell; Justin M Balko; Caitlin Bowman; Elizabeth J Davis; David D Chism; Leora Horn; Georgina V Long; Matteo S Carlino; Benedicte Lebrun-Vignes; Zeynep Eroglu; Jessica C Hassel; Alexander M Menzies; Jeffrey A Sosman; Ryan J Sullivan; Javid J Moslehi; Douglas B Johnson Journal: JAMA Oncol Date: 2018-12-01 Impact factor: 31.777
Authors: N Shaverdian; J Beattie; M Thor; M Offin; A F Shepherd; D Y Gelblum; A J Wu; C B Simone; M D Hellmann; J E Chaft; A Rimner; D R Gomez Journal: Ann Oncol Date: 2020-09-30 Impact factor: 32.976
Authors: Mark A Anderson; Vikram Kurra; William Bradley; Aoife Kilcoyne; Amirkasra Mojtahed; Susanna I Lee Journal: Br J Radiol Date: 2020-10-28 Impact factor: 3.039
Authors: Roberta Esposito; Teresa Fedele; Silvia Orefice; Vittoria Cuomo; Maria Prastaro; Mario Enrico Canonico; Federica Ilardi; Francesco De Stefano; Ludovica Fiorillo; Ciro Santoro; Giovanni Esposito Journal: Biomolecules Date: 2021-05-22