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Einsatz und Nebenwirkungen von Checkpoint-Inhibitoren

Indications and side effects of checkpoint inhibitors

  • Leitthema
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Der Nephrologe Aims and scope

Zusammenfassung

Checkpoint-Inhibitoren (CPI) haben die Therapie verschiedenster Erkrankungen grundlegend revolutioniert. Ihr Wirkmechanismus beruht auf der Aktivierung des Immunsystems, welches durch das Tumormilieu einer ständigen Suppression unterliegt. Tumorentitäten, die als besonders immunogen gelten, wie das Melanom oder das Nierenzellkarzinom, sind daher besonders für die Therapie mit CPI geeignet. Nebenwirkungen treten unter CPI Therapie insbesondere als immunvermittelte Nebenwirkungen auf und betreffen häufig den Magen-Darm-Trakt, die Haut und in selteneren Fällen die Hypophyse oder die Schilddrüse. Renale Nebenwirkungen scheinen deutlich häufiger aufzutreten als bisher angenommen und entsprechen histologisch meist einer akuten tubulointerstitiellen Nephritis. Immunvermittelte Nebenwirkungen sprechen generell gut auf die Gabe von Glukokortikoiden und Absetzen der CPI an. Der Einsatz von CPI bei Nierentransplantatempfängern hingegen scheint riskant zu sein; die Hälfte der behandelten Patienten verliert ihr Transplantat trotz intensivierter immunsuppressiver Therapie.

Abstract

Checkpoint inhibitors (CPI) have revolutionized the treatment of a wide variety of diseases. The mechanism of action of these biologicals is to reactivate the immune response against the tumor cells that is downregulated by the tumor stroma. Tumors that are thought to be particularly immunogenic, e.g. melanomas and renal cell carcinomas, are therefore particularly sensitive to treatment with CPI. Side effects induced by CPI are mainly represented by immune-mediated disorders that affect the gastrointestinal tract, the skin and in rare cases the pituitary and the thyroid glands. Side effects that affect the kidneys are more frequently encountered than initially suspected and mainly display histological features of an acute tubulointerstitial nephritis. Immune-mediated side effects induced by CPI are usually sensitive to withdrawal of these agents combined with administration of glucocorticoids. In contrast, CPI treatment of cancers in kidney transplant recipients is associated with substantial side effects that include loss of the graft in half of the treated patients despite intensive immunosuppressive treatment.

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Literatur

  1. Chin AI, Lam JS, Figlin RA, Belldegrun AS (2006) Surveillance strategies for renal cell carcinoma patients following nephrectomy. Rev Urol 8(1):1–7

    PubMed  PubMed Central  Google Scholar 

  2. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-part A: renal, penile, and testicular tumours. Eur Urol 70(1):93–105

    Article  PubMed  Google Scholar 

  3. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H (2002) An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol 168(6):2395–2400

    Article  PubMed  Google Scholar 

  4. Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17(8):2530–2540

    Article  CAS  PubMed  Google Scholar 

  5. Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27(34):5794–5799

    Article  CAS  PubMed  Google Scholar 

  6. Escudier B, Porta C, Schmidinger M, Rioux-Leclercq N, Bex A, Khoo V et al (2019) Renal cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 30(5):706–720

    Article  CAS  PubMed  Google Scholar 

  7. Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK et al (2018) Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378(14):1277–1290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Motzer RJ, Penkov K, Haanen J, Rini B, Albiges L, Campbell MT et al (2019) Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med 380(12):1103–1115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang Y, Zhou S, Yang F, Qi X, Wang X, Guan X et al (2019) Treatment-related adverse events of PD‑1 and PD-L1 inhibitors in clinical trials: a systematic review and meta-analysis. JAMA Oncol 5(7):1008–1019

    Article  PubMed  Google Scholar 

  10. Cortazar FB, Marrone KA, Troxell ML, Ralto KM, Hoenig MP, Brahmer JR et al (2016) Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int 90(3):638–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wanchoo R, Karam S, Uppal NN, Barta VS, Deray G, Devoe C et al (2017) Adverse renal effects of immune checkpoint inhibitors: a narrative review. Am J Nephrol 45(2):160–169

    Article  CAS  PubMed  Google Scholar 

  12. Manohar S, Kompotiatis P, Thongprayoon C, Cheungpasitporn W, Herrmann J, Herrmann SM (2019) Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis. Nephrol Dial Transplant 34(1):108–117

    Article  PubMed  Google Scholar 

  13. Menke J, Lucas JA, Zeller GC, Keir ME, Huang XR, Tsuboi N et al (2007) Programmed death 1 ligand (PD-L) 1 and PD-L2 limit autoimmune kidney disease: distinct roles. J Immunol 179(11):7466–7477

    Article  CAS  PubMed  Google Scholar 

  14. Haanen J, Carbonnel F, Robert C, Kerr KM, Peters S, Larkin J et al (2017) Management of toxicities from immunotherapy: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 28(4):iv119–iv42

    Article  CAS  PubMed  Google Scholar 

  15. Abdel-Wahab N, Safa H, Abudayyeh A, Johnson DH, Trinh VA, Zobniw CM et al (2019) Checkpoint inhibitor therapy for cancer in solid organ transplantation recipients: an institutional experience and a systematic review of the literature. J Immunother Cancer 7(1):106

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Nierenzentrum Heidelberg, Im Neuenheimer Feld 162, 69120, Heidelberg, Deutschland

    S. Delecluse &  M. Zeier

  2. Deutsches Krebsforschungszentrum (DKFZ), Einheit F100, Heidelberg, Deutschland

    S. Delecluse

  3. Medizinische Klinik V, Hämatologie, Onkologie und Rheumatologie, Universitätsklinikum Heidelberg, Heidelberg, Deutschland

    S. Zschäbitz & N. R. Neuendorff

Authors
  1. S. Delecluse
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  2. S. Zschäbitz
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  3. N. R. Neuendorff
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  4. M. Zeier
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Correspondence to S. Delecluse.

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Interessenkonflikt

S. Delecluse, S. Zschäbitz, N. R. Neuendorff und M. Zeier geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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U. Heemann, München

U. Kunzendorf, Kiel

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Delecluse, S., Zschäbitz, S., Neuendorff, N.R. et al. Einsatz und Nebenwirkungen von Checkpoint-Inhibitoren. Nephrologe 15, 87–94 (2020). https://doi.org/10.1007/s11560-020-00402-0

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  • DOI: https://doi.org/10.1007/s11560-020-00402-0

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