Zusammenfassung
Hintergrund
Durch den Einsatz von Checkpointinhibitoren sind Intensivmediziner in Zukunft mit einer zunehmenden Inzidenz an potenziell schwerwiegenden immunvermittelten Nebenwirkungen konfrontiert. Durch die vielfältigen Symptome ist die Diagnosestellung gerade für nicht onkologisch tätige Ärzte erschwert.
Fragestellung
Diagnostik und Therapie von immunvermittelten Nebenwirkungen durch Checkpointinhibitoren mit Schwerpunkt auf intensivmedizinisch relevante Verläufe.
Material und Methoden
Literaturrecherche und Zusammenfassung von aktuellen Veröffentlichungen zur Inzidenz, Klinik und Therapie von intensivmedizinisch relevanten Nebenwirkungen unter dem Einsatz von Checkpointinhibitoren.
Ergebnisse
Immunvermittelte Nebenwirkungen durch Checkpointinhibitoren sind schwierig zu diagnostizieren und zeigen verschiedenste Symptome. Schwerwiegende Verläufe können durch eine rechtzeitig eingeleitete Therapie verhindert werden.
Schlussfolgerungen
Die Einleitung einer frühen und standardisierten Therapie entsprechend des Schweregrads der auftretenden Nebenwirkungen kann potenziell tödliche Verläufe verhindern.
Abstract
Background
Due to the use of checkpoint inhibitors, intensive care units will be confronted with an increasing number of patients with immune-related adverse events. A broad spectrum of symptoms and potentially lethal consequences make diagnosis and treatment challenging.
Objectives
Diagnosis and treatment of immune-related adverse events in the treatment with checkpoint inhibitors with a special focus on intensive care units.
Materials and methods
Review of current publications about incidence, symptoms and treatment of adverse events after the use of checkpoint inhibitors relevant for intensive care medicine.
Results
Immune-related adverse events during therapy with checkpoint inhibitors are difficult to diagnose and present with various symptoms. Severe complications can often successfully be treated with early therapy.
Conclusions
The early treatment of immune-related adverse events according to their severity is needed to prevent a potentially life-threatening course.
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Literatur
Kochanek M, Staudinger T (2013) Der onkologische Patient in der Intensivmedizin. Med Klin Intensivmed Notfmed 108:182–183
Dine J, Gordon R, Shames Y et al (2017) Immune checkpoint inhibitors: an innovation in immunotherapy for the treatment and management of patients with cancer. Asia-Pac J Oncol Nurs 4:127–135
Ledford H (2011) Melanoma drug wins US approval. Nature 471:561
Hodi FS, O’day SJ, Mcdermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723
Mahoney KM, Rennert PD, Freeman GJ (2015) Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov 14:561–584
Borghaei H, Paz-Ares L, Horn L et al (2015) Nivolumab versus Docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:1627–1639
Reck M, Rodriguez-Abreu D, Robinson AG et al (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833
Modifiziert nach Sevier Medical. CC BY 3.0; https://creativecommons.org/licenses/by/3.0/deed.de. Zugegriffen: 23. Nov. 2018
Robert C, Schachter J, Long GV et al (2015) Pembrolizumab versus Ipilimumab in advanced melanoma. N Engl J Med 372:2521–2532
Naidoo J, Page DB, Li BT et al (2015) Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 26:2375–2391
Postow MA, Sidlow R, Hellmann MD (2018) Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 378:158–168
Brahmer JR, Lacchetti C, Schneider BJ et al (2018) Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 36:1714–1768
https://www.eortc.be/services/doc/ctc/ctcae_4.03_2010-06-14_Quickreference_5x7.pdf (abgerufen am 13. Aug. 2018). Zugegriffen: 09.12.2018
Wolchok JD, Weber JS, Hamid O et al (2010) Ipilimumab efficacy and safety in patients with advanced melanoma: a retrospective analysis of HLA subtype from four trials. Cancer Immun 10:9
Dubin K, Callahan MK, Ren B et al (2016) Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun 7:10391
Belum VR, Benhuri B, Postow MA et al (2016) Characterisation and management of dermatologic adverse events to agents targeting the PD-1 receptor. Eur J Cancer 60:12–25
Overkamp F (2016) Checkpointinhibitoren: Im Fokus – Immunvermittelte Nebenwirkungen. Dtsch Arztebl 113(6):34
Waidmann OT, Trojan J (2017) Immunvermittelte Nebenwirkungen unter Checkpointinhibitoren. Gastroenterologe 12:490–495
Gonzalez-Rodriguez E, Rodriguez-Abreu D, Spanish Group for Cancer Immuno-Biotherapy (GETICA) (2016) Immune checkpoint inhibitors: review and management of endocrine adverse events. Oncologist 21:804–816
Khunger M, Rakshit S, Pasupuleti V et al (2017) Incidence of pneumonitis with use of programmed death 1 and programmed death-ligand 1 inhibitors in non-small cell lung cancer: a systematic review and meta-analysis of trials. Chest 152:271–281
Naidoo J, Wang X, Woo KM et al (2017) Pneumonitis in patients treated with anti-programmed death-1/programmed death ligand 1 therapy. J Clin Oncol 35:709–717
Johnson DB, Balko JM, Compton ML et al (2016) Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med 375:1749–1755
Spain L, Walls G, Julve M et al (2017) Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann Oncol 28:377–385
Haanen JBAG, Carbonnel F, Robert C et al (2017) Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28:119–142
Horvat TZ, Adel NG, Dang TO et al (2015) Immune-related adverse events, need for systemic immunosuppression, and effects on survival and time to treatment failure in patients with melanoma treated with Ipilimumab at Memorial Sloan Kettering Cancer Center. J Clin Oncol 33:3193–3198
Weber JS, Hodi FS, Wolchok JD et al (2017) Safety profile of Nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 35:785–792
Santini FG, Rizvi H, Wilkins O et al (2017) Safety of retreatment with immunotherapy after immune-related toxicity in patients with lung cancers treated with anti-PD(L)-1 therapy. J Clin Oncol 35:9012–9012
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Y. d’Hargues, J. Prinz, P. Gödel, A. Shimabukuro-Vornhagen und M. Kochanek geben an, dass kein Interessenkonflikt besteht. B. Böll erhielt Honorare und/oder Forschungsunterstützung von Baxalta, Celgene, MSD, Astellas, Johnson & Johnson, Takeda, und Mundipharma außerhalb der vorliegenden Arbeit.
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d’Hargues, Y., Prinz, J., Gödel, P. et al. Diagnostik und Therapie von immunvermittelten Nebenwirkungen durch Checkpointinhibitoren in der Intensivmedizin. Med Klin Intensivmed Notfmed 115, 281–285 (2020). https://doi.org/10.1007/s00063-018-0521-z
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DOI: https://doi.org/10.1007/s00063-018-0521-z