Immuncheckpoint-Inhibitoren: Aktuelle Indikationen und mögliche zukünftige Konzepte

Max Schlaak; Christian Baues; Maike Trommer-Nestler; Carola Berking; Claus Belka; Sebastian Theurich

doi:10.1055/s-0043-125001

DMW - Deutsche Medizinische Wochenschrift, Table of Contents

Dtsch Med Wochenschr 2018; 143(14): 1014-1021
DOI: 10.1055/s-0043-125001

Dossier

Immuncheckpoint-Inhibitoren: Aktuelle Indikationen und mögliche zukünftige Konzepte

Immuncheckpoint Inhibitors: Current Indications and Possible Future Concepts

Max Schlaak

,

Christian Baues

,

Maike Trommer-Nestler

,

Carola Berking

,

Claus Belka

,

Sebastian Theurich

Abstract

Immuno-oncological therapy concepts have already achieved great success in the treatment of a number of advanced malignancies, thereby rapidly gaining access to clinical practice. Immuncheckpoint inhibitors are also being reviewed in the adjuvant setting. In malignant melanoma, they have already shown efficacy. Different combination strategies of Immuncheckpoint inhibitors are currently undergoing clinical evaluation to further improve treatment outcomes. However, this has so far also been associated with a significantly increased immune-mediated rate of side effects. Effective and safe immuno-oncology requires good clinical management of immune-mediated side effects. Radiological assessment is challenging under immunotherapy and requires new standards (iRECIST). Encouraging is the fact that immunotherapy also causes long-term remissions in some of the patients. This raises the hope for a fundamentally curative potential of immuno-oncological therapeutic approaches.

Immunonkologische Konzepte haben in den letzten Jahren Einzug in die klinische Routinebehandlung gehalten. Entitätsübergreifend werden sie bei einer Reihe von fortgeschrittenen Tumorerkrankungen eingesetzt. Eine Übersicht der aktuell zugelassenen Immuncheckpoint-Inhibitoren sowie eine Auswahl aktueller und zukünftiger Therapiemöglichkeiten und Besonderheiten des klinischen Managements bei immunonkologischen Behandlungen zeigt dieser Beitrag.

Schlüsselwörter

Immunonkologie - malignes Melanom - abskopaler Effekt - Radioonkologie - Langzeitremission

Key words

immuno-oncology - malignant melanoma - abscopic effect - radio-oncology - long-term remission

Full Text

References

Literatur
1 Ferris RL, Blumenschein GJ, Fayette J. et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. New England Journal of Medicine 2016; 375: 1856-1867 . doi:10.1056/NEJMoa1602252
2 Sharma P, Callahan MK, Bono P. et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. The Lancet Oncology 2016; 17: 1590-1598 . doi:10.1016/S1470-2045(16)30496-X
3 Motzer RJ, Escudier B, McDermott DF. et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. New England Journal of Medicine 2015; 373: 1803-1813 . doi:10.1056/NEJMoa1510665
4 Younes A, Santoro A, Shipp M. et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. The Lancet Oncology 2016; 17: 1283-1294 . doi:10.1016/S1470-2045(16)30167-X
5 Garon EB, Rizvi NA, Hui R. et al. Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer. New England Journal of Medicine 2015; 372: 2018-2028 . doi:10.1056/NEJMoa1501824
6 Kaufman HL, Russell J, Hamid O. et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. The Lancet Oncology 2016; 17: 1374-1385 . doi:10.1016/S1470-2045(16)30364-3
7 Schadendorf D, Hodi FS, Robert C. et al. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol 2015; 33: 1889-1894 . doi:10.1200/JCO.2014.56.2736
8 Wolchok JD, Chiarion-Sileni V, Gonzalez R. et al. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. New England Journal of Medicine 2017; 377: 1345-1356 . doi:10.1056/NEJMoa1709684
9 Nobler MP. The abscopal effect in malignant lymphoma and its relationship to lymphocyte circulation. Radiology 1969; 93: 410-412 . doi:10.1148/93.2.410
10 Postow MA, Callahan MK, Barker CA. et al. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med 2012; 366: 925-931 . doi:10.1056/NEJMoa1112824
11 Theurich S, Rothschild SI, Hoffmann M. et al. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma. Cancer Immunol Res 2016; 4: 744-754 . doi:10.1158/2326-6066.CIR-15-0156
12 Silk AW, Bassetti MF, West BT. et al. Ipilimumab and radiation therapy for melanoma brain metastases. Cancer Med 2013; 2: 899-906 . doi:10.1002/cam4.140
13 Aboudaram A, Modesto A, Chaltiel L. et al. Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination. Melanoma Res 2017; 27: 485-491 . doi:10.1097/CMR.0000000000000386
14 Hiniker SM, Reddy SA, Maecker HT. et al. A Prospective Clinical Trial Combining Radiation Therapy With Systemic Immunotherapy in Metastatic Melanoma. Int J Radiat Oncol Biol Phys 2016; 96: 578-588 . doi:10.1016/j.ijrobp.2016.07.005
15 Twyman-Saint Victor C, Rech AJ, Maity A. et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature 2015; 520: 373-377 . doi:10.1038/nature14292
16 Deng L, Liang H, Burnette B. et al. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest 2014; 124: 687-695 . doi:10.1172/JCI67313
17 Romano E, Scordo M, Dusza SW. et al. Site and Timing of First Relapse in Stage III Melanoma Patients: Implications for Follow-Up Guidelines. Journal of Clinical Oncology 2010; 28: 3042-3047 . doi:10.1200/JCO.2009.26.2063
18 Eggermont AMM, Chiarion-Sileni V, Grob JJ. et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase 3 trial. The Lancet Oncology 2015; 16: 522-530 . doi:10.1016/S1470-2045(15)70122-1
19 Weber J, Mandala M, Del Vecchio M. et al. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. New England Journal of Medicine 2017; 377: 1824-1835 . doi:10.1056/NEJMoa1709030
20 Kähler KC, Hassel JC, Heinzerling L. et al. Nebenwirkungsmanagement bei Immun-Checkpoint-Blockade durch CTLA-4- und PD1-Antikörper beim metastasierten Melanom. JDDG – Journal of the German Society of Dermatology 2016; 14: 662-683 . doi:10.1111/ddg.13047_g
21 Eigentler TK, Hassel JC, Berking C. et al. Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treat Rev 2016; 45: 7-18 . doi:10.1016/j.ctrv.2016.02.003
22 Hassel JC, Heinzerling L, Aberle J. et al. Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Cancer Treat Rev 2017; 57: 36-49 . doi:10.1016/j.ctrv.2017.05.003
23 Schwartz LH, Seymour L, Litiere S. et al. RECIST 1.1 – Standardisation and disease-specific adaptations: Perspectives from the RECIST Working Group. Eur J Cancer 2016; 62: 138-145 . doi:10.1016/j.ejca.2016.03.082
24 Seymour L, Bogaerts J, Perrone A. et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol 2017; 18: e143-e152 . doi:10.1016/S1470-2045(17)30074-8