Immune checkpoint inhibitor toxicities: systems-based approaches to improve patient care and research
Abstract
Immune checkpoint inhibitors (ICIs) have now been approved in numerous and diverse cancer types and combination regimens. Effective recognition and treatment of ICI toxicities, which might occur acutely, affect any organ system, and produce many distinct clinical syndromes, have emerged as essential goals of ICI management. Thus, developing robust diagnostic and management approaches for ICI toxicity across the health-care system is an urgent and unmet clinical need. In this Personal View, we describe barriers to high-quality care that have constrained the most effective management of patients with cancer receiving ICI treatment. We review education initiatives to enhance patient and physician awareness, which is necessary given the broad spectrum of ICI toxicities often experienced by patients, and assess various systems-based approaches that maximise the chances of appropriate management. In addition, we describe research pipelines that broaden evidence-based approaches and the pathobiology of these novel events. Developing effective, systematic approaches for the recognition and treatment of ICI toxicities will continue to grow in importance as these agents proliferate in cancer care.
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ICI targeting PD-1 and CTLA-4 is clinically effective in enhancing T-cell-mediated antitumor responses.
“Although proving to be clinically effective in enhancing T-cell-mediated antitumor responses”
From Autoimmune Myocarditis, Old Dogs and New Tricks. (2024) · cites this paper as [170]
Cites
Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Wolchok, J. D., Chiarion-Sileni, V., Gonzalez, R., Rutkowski, P., Grob, J.-J., Cowey, C. L., Lao, C. D., Wagstaff, J., Schadendorf, D., Ferrucci, P. F., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1709684 · Cited by 5,357 · see citing works
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
Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma
Larkin, J., Chiarion-Sileni, V., Gonzalez, R., Grob, J.-J., Rutkowski, P., Lao, C. D., Cowey, C. L., Schadendorf, D., Wagstaff, J., Dummer, R., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1910836 · Cited by 3,723 · see citing works
Haanen, 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
Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma
Weber, J., Mandala, M., Del Vecchio, M., Gogas, H. J., Arance, A. M., Cowey, C. L., Dalle, S., Schenker, M., Chiarion-Sileni, V., Marquez-Rodas, I., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1709030 · Cited by 2,246 · see citing works
Dubin, 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
Menzies, A. M., Johnson, D. B., Ramanujam, S., Atkinson, V. G., Wong, A. N. M., Park, J. J., McQuade, J. L., Shoushtari, A. N., Tsai, K. K., Eroglu, Z., et al. (2017) · Annals of Oncology · doi:10.1093/annonc/mdw443 · Cited by 817 · see citing works
Self-citationIwama, 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
Ipilimumab Therapy in Patients With Advanced Melanoma and Preexisting Autoimmune Disorders
Johnson, D. B., Sullivan, R. J., Ott, P. A., Carlino, M. S., Khushalani, N. I., Ye, F., Guminski, A., Puzanov, I., Lawrence, D. P., Buchbinder, E. I., et al. (2016) · JAMA Oncology · doi:10.1001/jamaoncol.2015.4368 · Cited by 642 · see citing works
Self-citationFaje, A. T., Lawrence, D., Flaherty, K., Freedman, C., Fadden, R., Rubin, K., Cohen, J., & Sullivan, R. J. (2018) · Cancer · doi:10.1002/cncr.31629 · Cited by 486 · see citing works
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
Tocilizumab for the management of immune mediated adverse events secondary to PD-1 blockade
Stroud, C. R., Hegde, A., Cherry, C., Naqash, A. R., Sharma, N., Addepalli, S., Cherukuri, S., Parent, T., Hardin, J., & Walker, P. (2019) · Journal of Oncology Pharmacy Practice · doi:10.1177/1078155217745144 · Cited by 331 · see citing works
Vedolizumab treatment for immune checkpoint inhibitor-induced enterocolitis
Bergqvist, V., Hertervig, E., Gedeon, P., Kopljar, M., Griph, H., Kinhult, S., Carneiro, A., & Marsal, J. (2017) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-017-1962-6 · Cited by 234 · see citing works
Alemtuzumab for Immune-Related Myocarditis Due to PD-1 Therapy
Esfahani, K., Buhlaiga, N., Thébault, P., Lapointe, R., Johnson, N. A., & Miller, W. H. (2019) · New England Journal of Medicine · doi:10.1056/nejmc1903064 · Cited by 224 · see citing works
Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors
Hasan Ali, O., Berner, F., Bomze, D., Fässler, M., Diem, S., Cozzio, A., Jörger, M., Früh, M., Driessen, C., Lenz, T. L., et al. (2019) · European Journal of Cancer · doi:10.1016/j.ejca.2018.11.009 · Cited by 187 · see citing works
Johnson, 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-citationCappelli, L. C., Dorak, M. T., Bettinotti, M. P., Bingham, C. O., & Shah, A. A. (2019) · Rheumatology · doi:10.1093/rheumatology/key358 · Cited by 111 · see citing works
Safety and efficacy of anti-PD-1 in patients with baseline cardiac, renal, or hepatic dysfunction
Kanz, B. A., Pollack, M. H., Johnpulle, R., Puzanov, I., Horn, L., Morgans, A., Sosman, J. A., Rapisuwon, S., Conry, R. M., Eroglu, Z., et al. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0166-5 · Cited by 75 · see citing works
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Endocrine toxicities of immune checkpoint inhibitors
Wright, J. J., Powers, A. C., & Johnson, D. B. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00484-3 · Cited by 441 · see citing works
Self-citationImmune checkpoint inhibitor–associated myocarditis: manifestations and mechanisms
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
Self-citationLehmann, 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-citationSex-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-citationAutoimmune 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
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- Authors
- Johnson, D. B., Reynolds, K. L., Sullivan, R. J., Balko, J. M., Patrinely, J. R., Cappelli, L. C., Naidoo, J., & Moslehi, J. J.
- Affiliations
- Vanderbilt-Ingram Cancer Center (US)
- Massachusetts General Hospital (US)
- Vanderbilt University (US)
- Johns Hopkins University (US)
- Corresponding author
- Johnson, Douglas B
- ORCID
- Venue
- The Lancet Oncology
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 21
- Issue
- 8
- Pages
- e398-e404
- ISSN
- 1470-2045 (ISSN-L)
- OpenAlex
- W3047192227
- Cited by
- 118
- References
- 18
- Citations by year
- 2026: 11 · 2025: 9 · 2024: 21 · 2023: 16 · 2022: 30 · 2021: 26 · 2020: 5
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Lancet Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (K23 CA204726, R01-HL14146, R01CA227481)
- National Cancer Institute
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K23-AR075872)
- Melanoma Research Foundation
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- immune checkpoint inhibitors, immune-related adverse events, systems approach, diagnostic approach, research pipeline, cancer care
- MeSH terms
- Antineoplastic Agents, Immunological, Patient Care, Humans, Medical Oncology, Neoplasms, Patient Education as Topic
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