Fulminant Myocarditis with Combination Immune Checkpoint Blockade
Open accessAbstract
Summ a r yImmune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy.We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab.In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates.Selective clonal T-cell populations infiltrating the myocardium were identical to those present in tumors and skeletal muscle.Pharmacovigilance studies show that myocarditis occurred in 0.27% of patients treated with a combination of ipilimumab and nivolumab, which suggests that our patients were having a rare, potentially fatal, T-cell-driven drug reaction.(Funded by Vanderbilt-Ingram Cancer Center Ambassadors and others.)I mmune checkpoint inhibitors have transformed the treatment of several cancers by releasing restrained antitumor immune responses.1 Ipilimumab, an anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, and nivolumab, an anti-programmed death-1 (PD-1) antibody, have individually improved survival in patients with melanoma, and early results suggest that their combination further enhances antitumor activity and survival.[2][3][4][5] Other adverse events associated with these agents include dermatitis, endocrinopathies, colitis, hepatitis, and pneumonitis, which are all thought to arise from aberrant activation of autoreactive T cells.6,7 These toxic effects are more frequent and severe when ipilimumab and nivolumab are used in combination.4 Here, we report two cases of lethal myocarditis accompanied by myositis in patients treated with a combination of nivolumab and ipilimumab.
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Following ICI therapy, 40% of patients with myocarditis experience concomitant myositis, confirmed in mouse models.
“Following ICI therapy, 40% of patients with myocarditis experience concomitant myositis, confirmed in mouse models. 41,42,46,68,282”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
The Introduction and Results report two patients who developed both myocarditis and myositis after combination immune checkpoint therapy. They do not establish that this occurs in 40% of patients with myocarditis. The Discussion cites mouse models for mechanisms of myocarditis, not confirmation of the claimed co-occurrence rate. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredT cells targeting both heart and tumor antigens are involved in ICI myocarditis development.
“indicating the involvement of T cells targeting both heart and tumor antigens in myocarditis development.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
The Results report shared, expanded T-cell receptor sequences in heart and tumor tissue from two patients with checkpoint-inhibitor myocarditis. The Discussion presents T cells targeting shared or cross-reactive antigens as possible mechanisms, but also says the shared sequences could have different antigen specificities. It does not establish that the T cells targeted both heart and tumor antigens. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe discovery of α-MyHC-specific T cells in ICI myocarditis suggests potential involvement of autoreactive T cells targeting α-MyHC in the initiation and progression of other forms of myocarditis.
“This discovery suggests a potential involvement of autoreactive T cells targeting α -MyHC in the initiation and progression of other forms of myocarditis.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
The Results report T-cell infiltration and shared T-cell receptor sequences in the hearts, skeletal muscle, and tumors of two patients with ICI myocarditis. The Discussion suggests that understanding this toxicity may offer insight into idiopathic myocarditis, but says the antigens recognized by those T cells remain unidentified. It does not report a discovery of α-MyHC-specific T cells or implicate that antigen in other forms of myocarditis; page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRecent cases of ICI myocarditis have expanded insights into the role of α-MyHC-specific T cells in myocarditis development.
“Recent cases of ICI myocarditis have expanded our insights into the role of α -MyHC-specific T cells in myocarditis development. 41-46”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
The Results report T-cell infiltration and shared T-cell receptor sequences in the myocardium, skeletal muscle, and tumors of two patients with ICI myocarditis. But the Discussion says the antigens recognized by those T cells remain unidentified; our copy does not establish that they were α-MyHC-specific. (LLM, conf=0.88)
Experimental — accuracy not yet measuredirAEs affect a broad spectrum of organs, including the colon, liver, lungs, heart, nervous system, skin, and endocrine system.
“These events, which can be severe with combination immunotherapies, affect a broad spectrum of organs, including the colon, liver, lungs, heart, nervous system, skin, and endocrine system.5, 6, 7, 8”
From irAE-GPT: leveraging large language models to identify immune-related adverse events in electronic health records and clinical trial datasets (2026) · cites this paper as [5]
The Introduction (page unavailable) lists colitis, hepatitis, pneumonitis, dermatitis, and endocrinopathies as side effects, and reports two cases of myocarditis, supporting the colon, liver, lungs, skin, endocrine system, and heart portions of the claim. The supplied passages and a search for neurological adverse events do not support the nervous-system portion. (LLM, conf=0.88)
Experimental — accuracy not yet measured
ICI myocarditis may occur following ICI treatment in patients with cancer.
“one of the best examples of drug-induced lymphocytic myocarditis is ICI myocarditis, which may occur following ICI treatment in patients with cancer.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
T cells may play a role in driving the pathogenesis of ICI myocarditis.
“suggesting a potential role of T cells in driving the pathogenesis of this condition.”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
Cardiac biopsies from patients with ICI myocarditis reveal myocardial infiltration primarily by T cells.
“Cardiac biopsies from patients with ICI myocarditis revealed myocardial infiltration primarily by T cells”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
In patients with cancer treated with ICIs, shared T-cell clones expand in the myocardium and tumor tissue.
“an early clinical case report on ICI myocarditis observed an expansion of shared T-cell clones in the myocardium and tumor tissue of patients with cancer treated with ICIs”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [46]
Shared antigens between tumor and normal tissue can cause de novo T cell activation and on-target off-tumor effects.
“Shared antigens between the tumor and normal tissue could lead to de novo T cell activation and precipitate on-target off-tumor effects”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Johnson et al., 2016
Infiltrating T cells have been observed in both tumor and cardiac muscle or skin in myocarditis and rash.
“This has been observed in both myocarditis and rash where infiltrating T cells have been observed in the tumor and in the cardiac muscle or skin, respectively”
From Hallmarks of response, resistance, and toxicity to immune checkpoint blockade (2021) · cites this paper as Johnson et al., 2016
T-cell receptor sequencing revealed common high-frequency TCRs in cardiac muscle, skeletal muscle and tumor.
“Deeper interrogation of the infiltrating T-cells through T-cell receptor (TCR) sequencing revealed common high-frequency TCRs in cardiac muscle, skeletal muscle and tumor.”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [28]
In a post-mortem study of two metastatic melanoma patients who developed fulminant myocarditis after nivolumab plus ipilimumab, infiltrating T-cells and macrophages were found in the myocardial tissue and the cardiac conduction system.
“In a post-mortem study of two metastatic melanoma patients who developed fulminant myocarditis after nivolumab plus ipilimumab, infiltrating T-cells and macrophages were found in the myocardial tissue and the cardiac conduction system [28].”
From Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors (2019) · cites this paper as [28]
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989 · see citing works
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,314 · see citing works
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155 · see citing works
Self-citationCombined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J. J., Cowey, C. L., Lao, C. D., Schadendorf, D., Dummer, R., Smylie, M., Rutkowski, P., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504030 · Cited by 8,157 · see citing works
PD-1 blockade induces responses by inhibiting adaptive immune resistance
Tumeh, P. C., Harview, C. L., Yearley, J. H., Shintaku, I. P., Taylor, E. J. M., Robert, L., Chmielowski, B., Spasic, M., Henry, G., Ciobanu, V., et al. (2014) · Nature · doi:10.1038/nature13954 · Cited by 6,609 · see citing works
Nivolumab in Previously Untreated Melanoma without <i>BRAF</i> Mutation
Robert, C., Long, G. V., Brady, B., Dutriaux, C., Maio, M., Mortier, L., Hassel, J. C., Rutkowski, P., McNeil, C., Kalinka-Warzocha, E., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1412082 · Cited by 5,519 · see citing works
Nivolumab and ipilimumab versus ipilimumab in untreated melanoma
Postow, M. A., Chesney, J., Pavlick, A. C., Robert, C., Grossmann, K., McDermott, D., Linette, G. P., Meyer, N., Giguere, J. K., Agarwala, S. S., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414428 · Cited by 2,781 · see citing works
Autoimmune Dilated Cardiomyopathy in PD-1 Receptor-Deficient Mice
Nishimura, H., Okazaki, T., Tanaka, Y., Nakatani, K., Hara, M., Matsumori, A., Sasayama, S., Mizoguchi, A., Hiai, H., Minato, N., et al. (2001) · Science · doi:10.1126/science.291.5502.319 · Cited by 1,868 · see citing works
Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab
Weber, J. S., Kähler, K. C., & Hauschild, A. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2012.41.6750 · Cited by 1,415 · see citing works
Cooper, L. T. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0800028 · Cited by 1,317 · see citing works
Eggermont, A. M. M., Chiarion-Sileni, V., Grob, J.-J., Dummer, R., Wolchok, J. D., Schmidt, H., Hamid, O., Robert, C., Ascierto, P. A., Richards, J. M., et al. (2015) · The Lancet Oncology · doi:10.1016/s1470-2045(15)70122-1 · Cited by 1,262 · see citing works
PD-1 Blockade with pembrolizumab in advanced Merkel-cell carcinoma
Nghiem, P. T., Bhatia, S., Lipson, E. J., Kudchadkar, R. R., Miller, N. J., Annamalai, L., Berry, S., Chartash, E. K., Daud, A., Fling, S. P., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603702 · Cited by 1,258 · see citing works
Self-citationDubin, K., Callahan, M. K., Ren, B., Khanin, R., Viale, A., Ling, L., No, D., Gobourne, A., Littmann, E., Huttenhower, C., et al. (2016) · Nature Communications · doi:10.1038/ncomms10391 · Cited by 987 · see citing works
Iwama, S., De Remigis, A., Callahan, M. K., Slovin, S. F., Wolchok, J. D., & Caturegli, P. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3008002 · Cited by 715 · see citing works
Okazaki, T., Tanaka, Y., Nishio, R., Mitsuiye, T., Mizoguchi, A., Wang, J., Ishida, M., Hiai, H., Matsumori, A., Minato, N., et al. (2003) · Nature Medicine · doi:10.1038/nm955 · Cited by 689 · see citing works
Viral myocarditis—diagnosis, treatment options, and current controversies
Pollack, A., Kontorovich, A. R., Fuster, V., & Dec, G. W. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.108 · Cited by 657 · see citing works
Using synthetic templates to design an unbiased multiplex PCR assay
Carlson, C. S., Emerson, R., Sherwood, A., Desmarais, C., Chung, M., Parsons, J. M., Steen, M. S., LaMadrid-Herrmannfeldt, M., Williamson, D. W., Livingston, R. J., et al. (2013) · Nature Communications · doi:10.1038/ncomms3680 · Cited by 568 · see citing works
Anti–PD-1–Related Pneumonitis during Cancer Immunotherapy
Nishino, M., Sholl, L. M., Hatabu, H., Ramaiya, N. H., & Hodi, F. S. (2015) · New England Journal of Medicine · doi:10.1056/nejmc1505197 · Cited by 373 · see citing works
Laubli, H. P., Balmelli, C., Bossard, M., Pfister, O., Glatz, K., & Zippelius, A. (2015) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-015-0057-1 · Cited by 320 · see citing works
Endothelial Programmed Death-1 Ligand 1 (PD-L1) Regulates CD8 + T-Cell–Mediated Injury in the Heart
Grabie, N., Gotsman, I., DaCosta, R., Pang, H. B., Stavrakis, G., Butte, M. J., Keir, M. E., Freeman, G. J., Sharpe, A. H., & Lichtman, A. H. (2007) · Circulation · doi:10.1161/circulationaha.107.709360 · Cited by 291 · see citing works
Self-citationPD-1 Protects against Inflammation and Myocyte Damage in T Cell-Mediated Myocarditis
Tarrio, M. L., Grabie, N., Bu, D.-X., Sharpe, A. H., & Lichtman, A. H. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200389 · Cited by 288 · see citing works
Self-citationKoelzer, V. H., Rothschild, S. I., Zihler, D., Wicki, A., Willi, B., Willi, N., Voegeli, M., Cathomas, G., Zippelius, A., & Mertz, K. D. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0117-1 · Cited by 200 · see citing works
Dynamics of the Cytotoxic T Cell Response to a Model of Acute Viral Infection
DeWitt, W. S., Emerson, R., Lindau, P., Vignali, M., Snyder, T. M., Desmarais, C., Sanders, C. M., Utsugi, H., Warren, E. H., McElrath, M. J., et al. (2015) · Journal of Virology · doi:10.1128/jvi.03474-14 · Cited by 161 · see citing works
Wolchok, J. D. (2015) · Cell · doi:10.1016/j.cell.2015.07.045 · Cited by 139 · see citing works
Griffin, L. D., Kearney, D. L., Ni, J., Jaffe, R., Fricker, F. J., Webber, S., Demmler, G. J., Gelb, B. D., & Towbin, J. A. (1995) · Cardiovascular Pathology · doi:10.1016/1054-8807(94)00025-m · Cited by 63 · see citing works
Sequence conservation predicts T cell reactivity against ragweed allergens
Pham, J. W., Oseroff, C., Hinz, D., et al. (2016) · Clinical & Experimental Allergy · doi:10.1111/cea.12772 · Cited by 18 · see citing works
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Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
Postow, M. A., Sidlow, R., & Hellmann, M. D. (2018) · New England Journal of Medicine · doi:10.1056/nejmra1703481 · Cited by 4,849 · see citing works
Brahmer, J. R., Lacchetti, C., Schneider, B. J., Atkins, M. B., Brassil, K. J., Caterino, J. M., Chau, I., Ernstoff, M. S., Gardner, J. M., Ginex, P., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6385 · Cited by 3,713 · see citing works
Self-citation2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.12.012 · Cited by 2,862 · see citing works
Wang, D. Y., Salem, J.-E., Cohen, J. V., Chandra, S., Menzer, C., Ye, F., Zhao, S., Das, S., Beckermann, K. E., Ha, L., et al. (2018) · JAMA Oncology · doi:10.1001/jamaoncol.2018.3923 · Cited by 2,674 · see citing works
Self-citationHaanen, J. B. A. G., Carbonnel, F., Robert, C., Kerr, K. M., Peters, S., Larkin, J., & Jordan, K. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx225 · Cited by 2,367 · see citing works
Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., Deswal, A., Drazner, M. H., Dunlay, S. M., Evers, L. R., et al. (2022) · Circulation · doi:10.1161/cir.0000000000001063 · Cited by 4,922 · see citing works
on behalf of the Society for Immunotherapy of Cancer Toxicity Management Working Group, Puzanov, I., Diab, A., Abdallah, K., Bingham, C. O., Brogdon, C., Dadu, R., Hamad, L., Kim, S., Lacouture, M. E., et al. (2017) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-017-0300-z · Cited by 1,992 · see citing works
Self-citationHallmarks of response, resistance, and toxicity to immune checkpoint blockade
Morad, G., Helmink, B. A., Sharma, P., & Wargo, J. A. (2021) · Cell · doi:10.1016/j.cell.2021.09.020 · Cited by 1,648 · see citing works
CTLA-4: a moving target in immunotherapy
Rowshanravan, B., Halliday, N., & Sansom, D. M. (2018) · Blood · doi:10.1182/blood-2017-06-741033 · Cited by 1,233 · see citing works
Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade
Benci, J. L., Xu, B., Qiu, Y., Wu, T. J., Dada, H., Twyman-Saint Victor, C., Cucolo, L., Lee, D. S. M., Pauken, K. E., Huang, A. C., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.022 · Cited by 1,216 · see citing works
Immune-related adverse events and anti-tumor efficacy of immune checkpoint inhibitors
Das, S., & Johnson, D. B. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0805-8 · Cited by 1,145 · see citing works
Self-citationCurigliano, G., Lenihan, D., Fradley, M., Ganatra, S., Barac, A., Blaes, A., Herrmann, J., Porter, C., Lyon, A. R., Lancellotti, P., et al. (2020) · Annals of Oncology · doi:10.1016/j.annonc.2019.10.023 · Cited by 1,031 · see citing works
Self-citationImmune-checkpoint inhibitors: long-term implications of toxicity
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Self-citationAmmirati, E., Frigerio, M., Adler, E. D., Basso, C., Birnie, D. H., Brambatti, M., Friedrich, M. G., Klingel, K., Lehtonen, J., Moslehi, J. J., et al. (2020) · Circulation: Heart Failure · doi:10.1161/circheartfailure.120.007405 · Cited by 811 · see citing works
Self-citationKociol, R. D., Cooper, L. T., Fang, J. C., Moslehi, J. J., Pang, P. S., Sabe, M. A., Shah, R. V., Sims, D. B., Thiene, G., Vardeny, O., et al. (2020) · Circulation · doi:10.1161/cir.0000000000000745 · Cited by 625 · see citing works
Self-citationThompson, J. A., Schneider, B. J., Brahmer, J., Andrews, S., Armand, P., Bhatia, S., Budde, L. E., Costa, L., Davies, M., Dunnington, D., et al. (2019) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2019.0013 · Cited by 570 · see citing works
Self-citationPalaskas, N., Lopez‐Mattei, J., Durand, J. B., Iliescu, C., & Deswal, A. (2020) · Journal of the American Heart Association · doi:10.1161/jaha.119.013757 · Cited by 535 · see citing works
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Luoma, A. M., Suo, S., Williams, H. L., Sharova, T., Sullivan, K., Manos, M., Bowling, P., Hodi, F. S., Rahma, O., Sullivan, R. J., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.001 · Cited by 484 · see citing works
Ammirati, E., Cipriani, M., Moro, C., Raineri, C., Pini, D., Sormani, P., Mantovani, R., Varrenti, M., Pedrotti, P., Conca, C., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.035319 · Cited by 452 · see citing works
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Self-citationIs autoimmunity the Achilles' heel of cancer immunotherapy?
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Self-citationPollack, M. H., Betof, A., Dearden, H., Rapazzo, K., Valentine, I., Brohl, A. S., Ancell, K. K., Long, G. V., Menzies, A. M., Eroglu, Z., et al. (2018) · Annals of Oncology · doi:10.1093/annonc/mdx642 · Cited by 393 · see citing works
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Self-citationMoving towards personalized treatments of immune-related adverse events
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Martini, E., Kunderfranco, P., Peano, C., Carullo, P., Cremonesi, M., Schorn, T., Carriero, R., Termanini, A., Colombo, F. S., Jachetti, E., et al. (2019) · Circulation · doi:10.1161/circulationaha.119.041694 · Cited by 341 · see citing works
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Johnson, D. B., Sullivan, R. J., & Menzies, A. M. (2017) · Cancer · doi:10.1002/cncr.30642 · Cited by 339 · see citing works
Santini, F. C., Rizvi, H., Plodkowski, A. J., Ni, A., Lacouture, M. E., Gambarin-Gelwan, M., Wilkins, O., Panora, E., Halpenny, D. F., Long, N. M., et al. (2018) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-17-0755 · Cited by 331 · see citing works
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Wei, S. C., Meijers, W. C., Axelrod, M. L., Anang, N.-A. A. S., Screever, E. M., Wescott, E. C., Johnson, D. B., Whitley, E., Lehmann, L., Courand, P.-Y., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0856 · Cited by 290 · see citing works
Self-citationChoueiri, T. K., Larkin, J., Oya, M., Thistlethwaite, F., Martignoni, M., Nathan, P., Powles, T., McDermott, D., Robbins, P. B., Chism, D. D., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30107-4 · Cited by 260 · see citing works
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237 · see citing works
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Moslehi, J., Lichtman, A. H., Sharpe, A. H., Galluzzi, L., & Kitsis, R. N. (2021) · Journal of Clinical Investigation · doi:10.1172/jci145186 · Cited by 237 · see citing works
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Denlinger, C. S., Sanft, T., Baker, K. S., Broderick, G., Demark-Wahnefried, W., Friedman, D. L., Goldman, M., Hudson, M., Khakpour, N., King, A., et al. (2018) · Journal of the National Comprehensive Cancer Network · doi:10.6004/jnccn.2018.0078 · Cited by 199 · see citing works
Self-citationExpansion of Pathogenic Cardiac Macrophages in Immune Checkpoint Inhibitor Myocarditis
Ma, P., Liu, J., Qin, J., Lai, L., Heo, G. S., Luehmann, H., Sultan, D., Bredemeyer, A., Bajapa, G., Feng, G., et al. (2024) · Circulation · doi:10.1161/circulationaha.122.062551 · Cited by 187 · see citing works
Self-citationBajwa, R., Cheema, A., Khan, T., Amirpour, A., Paul, A., Chaughtai, S., Patel, S., Patel, T., Bramson, J., Gupta, V., et al. (2019) · Journal of Clinical Medicine Research · doi:10.14740/jocmr3750 · Cited by 179 · see citing works
“The cases are illustrated in Table 3 below [95-102].”
BackgroundInfluentialLehmann, L. H., Cautela, J., Palaskas, N., Baik, A. H., Meijers, W. C., Allenbach, Y., Alexandre, J., Rassaf, T., Müller, O. J., Aras, M., et al. (2021) · JAMA Cardiology · doi:10.1001/jamacardio.2021.2241 · Cited by 178 · see citing works
Self-citationJohnson, D. B., McDonnell, W. J., Gonzalez-Ericsson, P. I., Al-Rohil, R. N., Mobley, B. C., Salem, J.-E., Wang, D. Y., Sanchez, V., Wang, Y., Chastain, C. A., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0523-2 · Cited by 176 · see citing works
Self-citationImmune checkpoint inhibitor toxicities
Marin-Acevedo, J. A., Chirila, R. M., & Dronca, R. S. (2019) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2019.03.012 · Cited by 160 · see citing works
Factors Associated With Immune Checkpoint Inhibitor–Related Myocarditis
Zamami, Y., Niimura, T., Okada, N., Koyama, T., Fukushima, K., Izawa-Ishizawa, Y., & Ishizawa, K. (2019) · JAMA Oncology · doi:10.1001/jamaoncol.2019.3113 · Cited by 139 · see citing works
Electrocardiographic Manifestations of Immune Checkpoint Inhibitor Myocarditis
Power, J. R., Alexandre, J., Choudhary, A., Ozbay, B., Hayek, S., Asnani, A., Tamura, Y., Aras, M., Cautela, J., Thuny, F., et al. (2021) · Circulation · doi:10.1161/circulationaha.121.055816 · Cited by 136 · see citing works
Self-citationWon, T., Kalinoski, H. M., Wood, M. K., Hughes, D. M., Jaime, C. M., Delgado, P., Talor, M. V., Lasrado, N., Reddy, J., & Čiháková, D. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111611 · Cited by 137 · see citing works
Autoimmune Myocarditis Caused by Immune Checkpoint Inhibitors Treated With Antithymocyte Globulin
Jain, V., Mohebtash, M., Rodrigo, M. E., Ruiz, G., Atkins, M. B., & Barac, A. (2018) · Journal of Immunotherapy · doi:10.1097/cji.0000000000000239 · Cited by 96 · see citing works
Cardiotoxicity of Anticancer Therapeutics
Dong, J., & Chen, H. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2018.00009 · Cited by 95 · see citing works
Product review: Avelumab, an anti-PD-L1 antibody
Collins, J. M., & Gulley, J. L. (2019) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2018.1551671 · Cited by 91 · see citing works
Epidemiology Characteristics and Outcome of Patients With Clinically Diagnosed Acute Myocarditis
Younis, A., Matetzky, S., Mulla, W., Masalha, E., Afel, Y., Chernomordik, F., Fardman, A., Goitein, O., Ben-Zekry, S., Peled, Y., et al. (2020) · The American Journal of Medicine · doi:10.1016/j.amjmed.2019.10.015 · Cited by 88 · see citing works
Sex-Specific Cardiovascular Risks of Cancer and Its Therapies
Wilcox, N. S., Rotz, S. J., Mullen, M., Song, E. J., Ky Hamilton, B., Moslehi, J., Armenian, S. H., Wu, J. C., Rhee, J.-W., & Ky, B. (2022) · Circulation Research · doi:10.1161/circresaha.121.319901 · Cited by 86 · see citing works
Self-citationB cell depletion or absence does not impede anti-tumor activity of PD-1 inhibitors
Damsky, W., Jilaveanu, L., Turner, N., Perry, C., Zito, C., Tomayko, M., Leventhal, J., Herold, K., Meffre, E., Bosenberg, M., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0613-1 · Cited by 78 · see citing works
Shah, K. P., Song, H., Ye, F., Moslehi, J. J., Balko, J. M., Salem, J.-E., & Johnson, D. B. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-19-0986 · Cited by 64 · see citing works
Self-citationFan, Z., Tian, Y., Chen, Z., Liu, L., Zhou, Q., He, J., Coleman, J., Dong, C., Li, N., Huang, J., et al. (2020) · EMBO Molecular Medicine · doi:10.15252/emmm.201911571 · Cited by 62 · see citing works
Myocardial Milieu Favors Local Differentiation of Regulatory T Cells
Delgobo, M., Weiß, E., Ashour, D., Richter, L., Popiolkowski, L., Arampatzi, P., Stangl, V., Arias-Loza, P., Mariotti-Ferrandiz, E., Rainer, P. P., et al. (2023) · Circulation Research · doi:10.1161/circresaha.122.322183 · Cited by 57 · see citing works
Immune checkpoint inhibitors associated cardiovascular immune-related adverse events
Jo, W., Won, T., Daoud, A., & Čiháková, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1340373 · Cited by 55 · see citing works
Autoimmune Myocarditis, Old Dogs and New Tricks.
Won, T., Song, E. J., Kalinoski, H. M., Moslehi, J. J., & Čiháková, D. (2024) · Circulation Research · doi:10.1161/circresaha.124.323816 · Cited by 51 · see citing works
Self-citationImmunotherapy to treat malignancy in patients with pre-existing autoimmunity
Boland, P., Pavlick, A. C., Weber, J., & Sandigursky, S. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2019-000356 · Cited by 50 · see citing works
Myeloid-derived suppressor cells are necessary for development of pulmonary hypertension
Bryant, A. J., Shenoy, V., Fu, C., Marek, G., Lorentsen, K. J., Herzog, E. L., Brantly, M. L., Avram, D., & Scott, E. W. (2018) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2017-0214oc · Cited by 47 · see citing works
Das, S., Ciombor, K. K., Haraldsdottir, S., Pumpalova, Y., Sahin, I. H., Pineda, G., Shyr, Y., Lin, E. P., Hsu, C.-Y., Chu, S.-K., et al. (2020) · The Oncologist · doi:10.1634/theoncologist.2019-0637 · Cited by 41 · see citing works
Perez-Shibayama, C., Gil-Cruz, C., Cadosch, N., Lütge, M., Cheng, H.-W., De Martin, A., Frischmann, K., Joachimbauer, A., Onder, L., Papadopoulou, I., et al. (2024) · Nature Cardiovascular Research · doi:10.1038/s44161-024-00432-0 · Cited by 35 · see citing works
Hughes, M. S., Zheng, H., Zubiri, L., Molina, G. E., Chen, S. T., Mooradian, M. J., Allen, I. M., Reynolds, K. L., & Dougan, M. (2019) · Cancer Medicine · doi:10.1002/cam4.2397 · Cited by 32 · see citing works
Uccello, G., Bonacchi, G., Rossi, V. A., Montrasio, G., & Beltrami, M. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm13010150 · Cited by 33 · see citing works
Hoefsmit, E. P., Rozeman, E. A., Haanen, J. B. A. G., & Blank, C. U. (2019) · ESMO Open · doi:10.1136/esmoopen-2018-000472 · Cited by 29 · see citing works
Koyama, J., Horiike, A., Yoshizawa, T., Dotsu, Y., Ariyasu, R., Saiki, M., Sonoda, T., Uchibori, K., Nishikawa, S., Kitazono, S., et al. (2019) · Journal of Thoracic Disease · doi:10.21037/jtd.2019.04.102 · Cited by 23 · see citing works
Bejan, C. A., Wang, M., Venkateswaran, S., Bergmann, E. A., Hiles, L., Xu, Y., Chandler, G. S., Brondfield, S., Silverstein, J., Wright, F., et al. (2026) · eBioMedicine · doi:10.1016/j.ebiom.2026.106227 · Cited by 16 · see citing works
Self-citationČiháková, D., Shi, Y., Adhikari, B., Bandettini, W. P., Cunningham, M. W., Danthi, N., Friedrich, M. G., Liu, P., Longacre, L. S., Mann, D. L., et al. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11195721 · Cited by 13 · see citing works
Joachimbauer, A., Perez-Shibayama, C., Payne, E., Hanka, I., Stadler, R., Papadopoulou, I., Rickli, H., Mäder, M. T., Borst, O., Zdanyte, M., et al. (2026) · medRxiv · doi:10.64898/2026.04.10.26350598 · Cited by 1 · see citing works
Jain, A., Bruno, K. A., Matsumori, A., Cooper, L. T., Yamani, M., & Fairweather, D. (2022) · Comprehensive Pharmacology · doi:10.1016/b978-0-12-820472-6.00091-8 · Cited by 1 · see citing works
- Authors
- Johnson, D. B., Balko, J. M., Compton, M. L., Chalkias, S., Gorham, J., Xu, Y., Hicks, M., Puzanov, I., Alexander, M. R., Bloomer, T. L., Becker, J. R., Slosky, D. A., Phillips, E. J., Pilkinton, M. A., Craig-Owens, L., Kola, N., Plautz, G., Reshef, D. S., Deutsch, J. S., Deering, R. P., Olenchock, B. A., Lichtman, A. H., Roden, D. M., Seidman, C. E., Koralnik, I. J., Seidman, J. G., Hoffman, R. D., Taube, J. M., Diaz, L. A., Anders, R. A., Sosman, J. A., & Moslehi, J. J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Brigham and Women's Hospital (US)
- ORCID
- Johnson, Douglas B.
- Balko, Justin M.
- Compton, Margaret L.
- Gorham, Joshua
- Xu, Yaomin
- Puzanov, Igor
- Alexander, Matthew R.
- Becker, Jason R.
- Phillips, Elizabeth J.
- Pilkinton, Mark A.
- Deering, Raquel P.
- Olenchock, Benjamin A.
- Lichtman, Andrew H.
- Roden, Dan M.
- Seidman, Christine E.
- Koralnik, Igor J.
- Seidman, Jonathan G.
- Hoffman, Robert D.
- Taube, Janis M.
- Diaz, Luis A.
- Anders, Robert A.
- Sosman, Jeffrey A.
- Moslehi, Javid J.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2016-11-03
- Volume
- 375
- Issue
- 18
- Pages
- 1749-1755
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC5247797
- OpenAlex
- W2547133566
- Semantic Scholar
- fe6be7d5f0af6d904fdc777ffa8fd382cdae7e9c
- Cited by
- 2,308
- References
- 26
- Citations by year
- 2026: 197 · 2025: 200 · 2024: 247 · 2023: 251 · 2022: 281 · 2021: 282 · 2020: 284 · 2019: 220 · 2018: 197 · 2017: 138 · 2016: 5
- FWCI
- 100.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (U01HL098153, U01HL098123, U01HL098162, U01HL098188, K08HL119355, R01HL121363, U01HL098163, U01HL098147)
- National Cancer Institute (K23CA204726, P50CA098131, R00CA181491, K12CA090625)
- National Institute of General Medical Sciences (P50GM115305)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac tumors and thrombi
- Keywords
- myocarditis, immune checkpoint inhibitors, ipilimumab, nivolumab, melanoma, immune-related adverse events, myositis, rhabdomyolysis, cardiac arrhythmias, CTLA-4, PD-1, T cell infiltration, pharmacovigilance, combination immunotherapy
- MeSH terms
- Ipilimumab, Nivolumab, Aged, Antibodies, Monoclonal, Arrhythmias, Cardiac, Electrocardiography, Female, Glucocorticoids, Heart Block, Humans, Immunotherapy, Male, Melanoma, Middle Aged, Myocarditis, Myocardium, Myositis, Fatal Outcome
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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