Multicenter Study

. 2025 Mar 3;13(3):e009364.

doi: 10.1136/jitc-2024-009364.

Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study

Amin H Nassar^#¹, Sarah Abou Alaiwi^#¹, Talal El Zarif^#¹, Ryan Denu², Walid Macaron², Noha Abdel-Wahab², Dory Freeman³, Alexi Vasbinder⁴, Salim Hayeck⁴, Elizabeth Anderson⁴, Rachel S Goodman⁵, Douglas B Johnson⁵, Shirly Grynberg⁶, Ronnie Shapira⁶, Jennifer M Kwan¹, Rachel Woodford⁷, Georgina V Long⁷, Tarek Haykal^{8

9}, Susan Dent⁸, Yuki Kojima¹⁰, Kan Yonemor¹⁰, Ankita Tandon¹¹, Alexandra Trevino¹², Nausheen Akhter¹², Eric H Yang¹³, Gavin Hui^{13

14}, Alexandra Drakaki^{13

14}, Edward El-Am¹⁵, Elie Kozaily¹⁵, Ahmad Al-Hader¹⁵, Elias Bou Farhat¹⁶, Priyanka Babu¹, Arjun Mittra¹⁷, Mingjia Li¹⁷, Nicholas Jones¹⁷, Javier Baena¹⁸, Mercedes Juarez Herrera¹⁸, Simone Foderaro¹⁹, Frank Aboubakar Nana²⁰, Chul Kim²¹, Paul Sackstein²¹, Kaushal Parikh²², Aakash P Desai²², Caleb Smith²², Alessio Cortellini^{23

24

25}, David J Pinato^{25

26}, James Korolewicz²⁵, Nerea Lopetegui-Lia²⁷, Pauline Funchain²⁷, Arrush Choudhary²⁸, Aarti Asnani²⁸, Vishal Navani²⁹, Daniel Meyers²⁹, Igor Stukalin²⁹, Jesus Antonio Ocejo Gallegos³⁰, Jonathan Trent³⁰, Sanober Nusrat³¹, Carmel Malvar³², Rana R McKay³², Tomas G Neilan³³, Toni K Choueiri^#³⁴, Abdul Rafeh Naqash^#³⁵

Affiliations

¹ Yale University School of Medicine, New Haven, Connecticut, USA.
² Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³ Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, Tennessee, USA.
⁶ Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.
⁷ Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
⁸ Duke Cancer Institute, School of Medicine, Duke University, Durham, North Carolina, USA.
⁹ Department of Internal Medicine, Division of medical Oncology, The Ohio State University College of Medicine, Columbus, Ohio, USA.
¹⁰ National Cancer Center Hospital, Tokyo, Japan.
¹¹ Department of Medical Oncology, Loyola University Medical Center, Maywood, Illinois.
¹² Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹³ UCLA Cardio-oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
¹⁴ Hematology/Oncology Department, David Geffen School of Medicine, Los Angeles, California, USA.
¹⁵ Department of Medicine, Indiana University School of Medicine Eskenazi Hospital, Indianapolis, Indiana, USA.
¹⁶ Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁷ Division of Medical Oncology, The Ohio State University, Columbus, Ohio, USA.
¹⁸ Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
¹⁹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
²⁰ Division of Pneumology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
²¹ Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, Washington, DC, USA.
²² Division of Medical Oncology, Mayo Clinic, Rochester, New York, USA.
²³ Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy.
²⁴ Department of Medicine and Surgery, Universitá Campus Bio-Medico di Roma, Roma, Italy.
²⁵ Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
²⁶ Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
²⁷ Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
²⁸ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
²⁹ Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
³⁰ Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
³¹ Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA.
³² Moores Cancer Center, University of California San Diego, La Jolla, California, USA.
³³ Cardio-Oncology Program, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁴ Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA abdulrafeh-naqash@ouhsc.edu toni_choueiri@dfci.harvard.edu.
³⁵ Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA abdulrafeh-naqash@ouhsc.edu toni_choueiri@dfci.harvard.edu.

^# Contributed equally.

PMID: 40032601
PMCID: PMC11877189
DOI: 10.1136/jitc-2024-009364

Multicenter Study

Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study

Amin H Nassar et al. J Immunother Cancer. 2025.

. 2025 Mar 3;13(3):e009364.

doi: 10.1136/jitc-2024-009364.

Authors

Affiliations

¹ Yale University School of Medicine, New Haven, Connecticut, USA.
² Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
³ Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁴ Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
⁵ Department of Medicine, Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center, Nashville, Tennessee, USA.
⁶ Ella Lemelbaum Institute of Immuno-Oncology, Sheba Medical Center, Ramat Gan, Israel.
⁷ Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
⁸ Duke Cancer Institute, School of Medicine, Duke University, Durham, North Carolina, USA.
⁹ Department of Internal Medicine, Division of medical Oncology, The Ohio State University College of Medicine, Columbus, Ohio, USA.
¹⁰ National Cancer Center Hospital, Tokyo, Japan.
¹¹ Department of Medical Oncology, Loyola University Medical Center, Maywood, Illinois.
¹² Division of Cardiology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
¹³ UCLA Cardio-oncology Program, Division of Cardiology, Department of Medicine, University of California at Los Angeles, Los Angeles, California, USA.
¹⁴ Hematology/Oncology Department, David Geffen School of Medicine, Los Angeles, California, USA.
¹⁵ Department of Medicine, Indiana University School of Medicine Eskenazi Hospital, Indianapolis, Indiana, USA.
¹⁶ Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹⁷ Division of Medical Oncology, The Ohio State University, Columbus, Ohio, USA.
¹⁸ Department of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
¹⁹ Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.
²⁰ Division of Pneumology, Cliniques universitaires Saint-Luc, Brussels, Belgium.
²¹ Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, DC, Washington, DC, USA.
²² Division of Medical Oncology, Mayo Clinic, Rochester, New York, USA.
²³ Operative Research Unit of Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy.
²⁴ Department of Medicine and Surgery, Universitá Campus Bio-Medico di Roma, Roma, Italy.
²⁵ Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK.
²⁶ Division of Oncology, Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy.
²⁷ Department of Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
²⁸ Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
²⁹ Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada.
³⁰ Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.
³¹ Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA.
³² Moores Cancer Center, University of California San Diego, La Jolla, California, USA.
³³ Cardio-Oncology Program, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts, USA.
³⁴ Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA abdulrafeh-naqash@ouhsc.edu toni_choueiri@dfci.harvard.edu.
³⁵ Stephenson Cancer Center, University of Oklahoma, Oklahoma City, Oklahoma, USA abdulrafeh-naqash@ouhsc.edu toni_choueiri@dfci.harvard.edu.

^# Contributed equally.

PMID: 40032601
PMCID: PMC11877189
DOI: 10.1136/jitc-2024-009364

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.

Keywords: Cardiotoxicity; Immune Checkpoint Inhibitor.

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Conflict of interest statement

Competing interests: AHN receives honoraria from OncLive, TEMPUS, and Korean Society for Medical Oncology. Consulting fees: Guidepoint Global. EHY: Research funding/grants from CSL Behring, Boehringer Ingelheim and Eli and Lilly, Bristol Myers Squibb, and Amgen. Consulting fees from Pfizer, Xencor. RRM: consultant/advisor: AstraZeneca, Ambrx, Aveo, Bayer, Blue Earth Diagnostics, Bristol-Myers Squibb, Calithera, Caris, Dendreon, Exelixis, Eisai, Johnson & Johnson, Lilly, Merck, Myovant, Novartis, Pfizer, Sanofi, Seagen, Sorrento, Telix, Tempus. AD: Ad Board/Consulting for: SeaGen, Astra Zeneca, Merck, EMD Serono, Exelixis, Eli Lilly, Infinity, Roche.DJP: Lecture fees: Bayer Healthcare, Astra Zeneca, EISAI, Bristol Myers-Squibb, Roche, Ipsen; Travel expenses: Bristol Myers-Squibb, Roche, Bayer Healthcare; Consulting fees: Mina Therapeutics, Boehringer Ingelheim, Ewopharma, EISAI, Ipsen, Roche, H3B, Astra Zeneca, DaVolterra, Mursla, Avammune Therapeutics, LiFT Biosciences, Exact Sciences; Research funding (to institution): MSD, BMS, GSK.Alessio Cortellini received grants for consultancies/advisory boards: BMS, MSD, OncoC4, IQVIA, Roche, GSK, AstraZeneca, Access Infinity, Ardelis Health and REGENERON. He also received speaker fees from AstraZeneca, EISAI, MSD, SANOFI/REGENERON and Pierre-Fabre. KN receives honorarium from Pfizer, Eisai, AstraZeneca, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, MSD, Boehringer Ingelheim, Ono, Daiichi-Sankyo, Bayer, Jansen, and Sanofi. Advisory board: Eisai, AstraZeneca, Sanofi, Genmab, Gliad, OncXerna, Takeda, Novartis, MSD, Henlius. Research support (to institution): MSD, Daiichi-Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. Principal investigator: MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Merck Biopharma Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Haihe. SG received honoraria from BMS, MSD, Sanofi, Novartis, Medison, Merck Serono. JE receives honoraria from Roche, AstraZeneca, and BMS. Consulting: Roche. Expert testimony: Roche. Travel expenses: MSD. SD: consultancy role with AstraZeneca, Gilead Sciences, Pfizer, Novartis, Myocardial Solutions, Eli Lilly none relevant to this manuscript. Funding: None. TKC reports: Institutional and/or personal, paid and/or unpaid support for research, advisory boards, consultancy, and/or honoraria past 5 years, ongoing or not, from: Alkermes, AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers-Squibb, Calithera, Circle Pharma, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, Gilead, HiberCell, IQVA, Infinity, Ipsen, Jansen, Kanaph, Lilly, Merck, Nikang, Neomorph, Nuscan/PrecedeBio, Novartis, Oncohost, Pfizer, Roche, Sanofi/Aventis, Scholar Rock, Surface Oncology, Takeda, Tempest, Up-To-Date, CME events (Peerview, OncLive, MJH, CCO and others), outside the submitted work; Institutional patents filed on molecular alterations and immunotherapy response/toxicity, and ctDNA; Equity: Tempest, Pionyr, Osel, Precede Bio, CureResponse, InnDura Therapeutics, Primium; Committees: NCCN, GU Steering Committee, ASCO/ESMO, ACCRU, KidneyCan; Medical writing and editorial assistance support may have been funded by Communications companies in part; No speaker’s bureau; Mentored several non-US citizens on research projects with potential funding (in part) from non-US sources/Foreign Components; The institution (Dana-Farber Cancer Institute) may have received additional independent funding from drug companies or/and royalties potentially involved in research around the subject matter; TKC is supported in part by the Dana-Farber/Harvard Cancer Center Kidney SPORE (2P50CA101942-16) and Program 5P30CA006516-56, the Kohlberg Chair at Harvard Medical School and the Trust Family, Michael Brigham, Pan Mass Challenge, Hinda and Arthur Marcus Fund and Loker Pinard Funds for Kidney Cancer Research at DFCI. ARN reports Funding to Institution for Trials he is PI on: Loxo@Lilly, Surface Oncology, ADC Therapeutics, IGM Biosciences, EMD Serono, Aravive, Nikang Therapeutics, Inspirna, Exelexis, Revolution Medicine, Jacobio, Pionyr, Jazz Pharmaceuticals, NGM Biopharmaceuticals. ARN receives Consultant Editor Compensation: JCO Precision Oncology. Consulting/Advisory Board: Foundation Med. ARN reports Travel Compensation from: SITC/ AACR/ Conquer Cancer Foundation, Jazz Pharmaceuticals, Binay Tara Foundation, Foundation Med Funding: None.

Figures

Figure 1. Distribution of trAEs in patients with cardiac metastasis treated with immune checkpoint inhibitor-based regimens. The sum of individual trAEs does not add up to the total as a subset of patients had more than one trAE. trAE, treatment-related adverse event.

Figure 2. Forest plot for patients with progression-free survival and overall survival data. Covariates are shown. Cox regression p values are indicated on the right. Bars represent the 95% CI. HNSCC, head and neck squamous cell carcinoma.

Figure 3. Survival outcomes for patients with cardiac metastasis among common tumor types. Progression-free survival (a) and overall survival (b) of 42 patients with cutaneous melanoma treated with immune checkpoint inhibitor (ICI)-based regimens. Progression-free survival (c) and overall survival (d) of 26 patients with NSCLC treated with ICI-based regimens. NSCLC, non-small cell lung cancer.

Figure 4. Concordance rates in overall response rate (ORR) between overall disease burden and cardiac mass. Solid lines refer to discordant ORRs. Dashed lines refer to concordant ORRs. (a) cutaneous melanoma (b) NSCLC. CR, complete response; NSCLC, non-small cell lung cancer; PR, partial response; SD: Stable disease; PD: Progressive disease.

See this image and copyright information in PMC

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Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study

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Safety and efficacy of immune checkpoint therapy for the treatment of patients with cardiac metastasis: a multicenter international retrospective study

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Conflict of interest statement

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