Journal for ImmunoTherapy of Cancer (Mar 2025)
Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study
- Nicholas Jones,
- Tarek Haykal,
- Noha Abdel-Wahab,
- Abdul Rafeh Naqash,
- Alessio Cortellini,
- Rana R McKay,
- Toni K Choueiri,
- Georgina V Long,
- Pauline Funchain,
- Sarah Abou Alaiwi,
- Amin H Nassar,
- Douglas B Johnson,
- Chul Kim,
- David J Pinato,
- Jonathan Trent,
- Vishal Navani,
- Alexandra Drakaki,
- Tomas G Neilan,
- Kaushal Parikh,
- Frank Aboubakar Nana,
- Eric H Yang,
- Elizabeth Anderson,
- Gavin Hui,
- Mingjia Li,
- Paul Sackstein,
- Shirly Grynberg,
- Jesus Antonio Ocejo Gallegos,
- Susan Dent,
- Ahmad Al-Hader,
- Ankita Tandon,
- Javier Baena,
- Yuki Kojima,
- Aakash P Desai,
- Arjun Mittra,
- Edward El-Am,
- Elie Kozaily,
- Rachel Woodford,
- Dory Freeman,
- Caleb Smith,
- Nausheen Akhter,
- Talal El Zarif,
- Ryan Denu,
- Walid Macaron,
- Alexi Vasbinder,
- Salim Hayeck,
- Rachel S Goodman,
- Ronnie Shapira,
- Jennifer M Kwan,
- Kan Yonemor,
- Alexandra Trevino,
- Elias Bou Farhat,
- Priyanka Babu,
- Mercedes Juarez Herrera,
- Simone Foderaro,
- James Korolewicz,
- Nerea Lopetegui-Lia,
- Arrush Choudhary,
- Aarti Asnani,
- Daniel Meyers,
- Igor Stukalin,
- Sanober Nusrat,
- Carmel Malvar
Affiliations
- Nicholas Jones
- Division of Medical Oncology, The Ohio State University, Columbus, Ohio, USA
- Tarek Haykal
- Duke Cancer Institute, School of Medicine, Duke University, Durham, North Carolina, USA
- Noha Abdel-Wahab
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Abdul Rafeh Naqash
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA
- Alessio Cortellini
- Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy
- Rana R McKay
- Moores Cancer Center, University of California San Diego, La Jolla, California, USA
- Toni K Choueiri
- Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA
- Georgina V Long
- Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia
- Pauline Funchain
- Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA
- Sarah Abou Alaiwi
- Yale University School of Medicine, New Haven, Connecticut, USA
- Amin H Nassar
- Yale University School of Medicine, New Haven, Connecticut, USA
- Douglas B Johnson
- Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, Tennessee, USA
- Chul Kim
- Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, Washington, DC, USA
- David J Pinato
- Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy
- Jonathan Trent
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
- Vishal Navani
- Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada
- Alexandra Drakaki
- UCLA Cardio-oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Tomas G Neilan
- Cardio-Oncology Program, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Kaushal Parikh
- Division of Medical Oncology, Mayo Clinic, Rochester, New York, USA
- Frank Aboubakar Nana
- Division of Pneumology, Cliniques universitaires Saint-Luc, Brussels, Belgium
- Eric H Yang
- UCLA Cardio-oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Elizabeth Anderson
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Gavin Hui
- UCLA Cardio-oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA
- Mingjia Li
- Division of Medical Oncology, The Ohio State University, Columbus, Ohio, USA
- Paul Sackstein
- Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, Washington, DC, USA
- Shirly Grynberg
- Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel
- Jesus Antonio Ocejo Gallegos
- Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA
- Susan Dent
- Duke Cancer Institute, School of Medicine, Duke University, Durham, North Carolina, USA
- Ahmad Al-Hader
- Department of Medicine, Indiana University School of Medicine Eskenazi Hospital, Indianapolis, Indiana, USA
- Ankita Tandon
- Department of Medical Oncology, Loyola University Medical Center, Maywood, Illinois
- Javier Baena
- Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain
- Yuki Kojima
- National Cancer Center Hospital, Tokyo, Japan
- Aakash P Desai
- Division of Medical Oncology, Mayo Clinic, Rochester, New York, USA
- Arjun Mittra
- Division of Medical Oncology, The Ohio State University, Columbus, Ohio, USA
- Edward El-Am
- Department of Medicine, Indiana University School of Medicine Eskenazi Hospital, Indianapolis, Indiana, USA
- Elie Kozaily
- Department of Medicine, Indiana University School of Medicine Eskenazi Hospital, Indianapolis, Indiana, USA
- Rachel Woodford
- Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia
- Dory Freeman
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
- Caleb Smith
- Division of Medical Oncology, Mayo Clinic, Rochester, New York, USA
- Nausheen Akhter
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Talal El Zarif
- Yale University School of Medicine, New Haven, Connecticut, USA
- Ryan Denu
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Walid Macaron
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
- Alexi Vasbinder
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Salim Hayeck
- Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- Rachel S Goodman
- Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, Tennessee, USA
- Ronnie Shapira
- Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel
- Jennifer M Kwan
- Yale University School of Medicine, New Haven, Connecticut, USA
- Kan Yonemor
- National Cancer Center Hospital, Tokyo, Japan
- Alexandra Trevino
- Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Elias Bou Farhat
- Brigham and Women’s Hospital, Boston, Massachusetts, USA
- Priyanka Babu
- Yale University School of Medicine, New Haven, Connecticut, USA
- Mercedes Juarez Herrera
- Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain
- Simone Foderaro
- Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy
- James Korolewicz
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK
- Nerea Lopetegui-Lia
- Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA
- Arrush Choudhary
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Aarti Asnani
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
- Daniel Meyers
- Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada
- Igor Stukalin
- Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada
- Sanober Nusrat
- Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA
- Carmel Malvar
- Moores Cancer Center, University of California San Diego, La Jolla, California, USA
- DOI
- https://doi.org/10.1136/jitc-2024-009364
- Journal volume & issue
-
Vol. 13,
no. 3
Abstract
Background Data on the safety profiles and clinical outcomes of patients with solid tumors and cardiac metastasis treated with immune checkpoint inhibitors (ICIs) are limited.Methods This is an international multicenter retrospective study of patients with cancer and cardiac metastasis at baseline. Patients who had received ≥1 dose of ICI were included. Treatment-related adverse events (trAEs) were graded per Common Terminology Criteria for Adverse Event V.5.0. Objective response rates (ORR) were evaluated by Response Evaluation Criteria in Solid Tumors V.1.1 when available. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method.Results Among 110 pts, median age at ICI initiation was 65 (IQR: 59–75). Median follow-up time since ICI initiation was 36 (95% CI: 26 to 51) months. Melanoma (38%, n=42) and non-small cell lung cancer (24%, n=26) were the most common. 68 (62%) patients received ICIs as first-line, and 29 (26%) patients were treated with combination anti-programmed death-1 and anti-cytotoxic T-lymphocyte antigen 4. The most common location of cardiac metastasis was in the atria (37%, n=41) and ventricles (35%, n=39). 15 patients (13.6%) had bilateral cardiac/pericardial metastasis, 44 (40%) had left-sided, and 43 (39.8%) had right-sided. At ICI initiation, 21% (n=23) had a cardiac thrombus. Cardiology referrals and cardiac MRIs at the time of cancer diagnosis were completed on 58 (53%) and 52 (47%) patients, respectively. Cardiac events occurred in 40 (36%) patients, including arrhythmias (n=14, 13%), arterial/venous emboli (n=4, 3.6%), and cardiac tamponade (n=3, 2.7%). 53 (47%) patients developed trAEs; most common were colitis/diarrhea (n=16, 15%), dermatitis (n=13, 12%), and hepatitis (n=9, 8.2%). ICI-related major cardiac trAEs occurred in 2 (1.8%) patients. 22 patients (20%) developed grade ≥3 trAE. Patients with multiple cardiac metastases had significantly lower responses to ICI-based regimens compared with patients with single cardiac metastasis (11% vs 63%, p=0.02). For melanoma, ORR, median PFS, and median OS were 38%, 9.0 months, and 28.9 months, respectively. 83% of patients with melanoma had concordant responses in overall disease burden and cardiac disease. 91 patients discontinued ICIs, and the main reason was progression or death in 55 (49%) patients.Conclusions Among patients with pre-existing cardiac metastasis, ICIs demonstrated meaningful clinical efficacy with no increase in safety signals. Most patients had concordant responses in the overall disease burden and cardiac mass. Multidisciplinary teams are crucial for the appropriate management of patients with cardiac metastasis.
