title: Cardiotoxicity associated with CTLA4 and PD1 blocking immunotherapy.
abstract: Immune-checkpoint blocking antibodies have demonstrated objective antitumor responses in multiple tumor types including melanoma, non-small cell lung cancer (NSCLC), and renal cell cancer (RCC). In melanoma, an increase in overall survival has been demonstrated with anti-CTLA-4 and PD-1 inhibition. However, a plethora of immune-mediated adverse events has been reported with these agents. Immune-mediated cardiotoxicity induced by checkpoint inhibitors has been reported in single cases with variable presentation, including myocarditis and pericarditis. Among six clinical cancer centers with substantial experience in the administration of immune-checkpoint blocking antibodies, eight cases of immune-related cardiotoxicity after ipilimumab and/or nivolumab/pembrolizumab were identified. Diagnostic findings, treatment and follow-up are reported. A large variety of cardiotoxic events with manifestations such as heart failure, cardiomyopathy, heart block, myocardial fibrosis and myocarditis was documented. This is the largest case series to date describing cardiotoxicity of immune-checkpoint blocking antibodies. Awareness, monitoring of patients with pre-existing cardiac disorders and prompt evaluation by the treatment team is essential. Treatment including application of steroids is critical for patient safety.
authors.affiliation: University Hospital Erlangen, Erlangen, Germany ; Department of Dermatology, University Hospital Erlangen, Ulmenweg 18, 91054 Erlangen, Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heinzerling
authors.affiliation: Dana Farber Cancer Institute, Boston, MA USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.affiliation: Dana Farber Cancer Institute, Boston, MA USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: University of Chicago Comprehensive Cancer Center and Pathology, Chicago, IL USA.
authors.forename: Aliya N
authors.initials: AN
authors.lastname: Husain
authors.affiliation: University Hospital Erlangen, Erlangen, Germany.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Tajmir-Riahi
authors.affiliation: University of Texas MD Anderson Center, Houston, TX USA.
authors.forename: Hussein
authors.initials: H
authors.lastname: Tawbi
authors.affiliation: Paracelsus University Hospital Nuremberg, Nürnberg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pauschinger
authors.affiliation: University of Chicago Comprehensive Cancer Center and Pathology, Chicago, IL USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Gajewski
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD USA.
authors.forename: Evan J
authors.initials: EJ
authors.lastname: Lipson
authors.affiliation: University of Chicago Comprehensive Cancer Center and Pathology, Chicago, IL USA.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Luke
keywords: Cardiomyopathy; Checkpoint inhibitor; Immune-related adverse events; Immunotherapy; Ipilimumab; Melanoma; Myocarditis; Nivolumab; Pembrolizumab