Management of Immune Checkpoint Blockade Dysimmune Toxicities

A Collaborative Position Paper

S. Champiat; O. Lambotte; E. Barreau; R. Belkhir; A. Berdelou; F. Carbonnel; C. Cauquil; P. Chanson; M. Collins; A. Durrbach; S. Ederhy; S. Feuillet; H. François; J. Lazarovici; J. Le Pavec; E. De Martin; C. Mateus; J.-M. Michot; D. Samuel; J.-C. Soria; C. Robert; A. Eggermont; A. Marabelle


Ann Oncol. 2016;27(4):559-574. 

In This Article

Abstract and Introduction


Monoclonal antibodies targeted against the immune checkpoint molecules CTLA-4 and PD-1 have recently obtained approval for the treatment of metastatic melanoma and advanced/refractory non small-cell lung cancers. Therefore, their use will not be limited anymore to selected hospitals involved in clinical trials. Indeed, they will be routinely prescribed in many cancer centers across the world. Besides their efficacy profile, these immune targeted agents also generate immune-related adverse events (irAEs). This new family of dysimmune toxicities remains largely unknown to the broad oncology community. Although severe irAEs remain rare (~10% of cases under monotherapy), they can become life-threatening if not anticipated and managed appropriately. Over the last 5 years, Gustave Roussy has accumulated a significant experience in the prescription of immune checkpoint blockade (ICB) antibodies and the management of their toxicities. Together with the collaboration of Gustave Roussy's network of organ specialists with expertise in irAEs, we propose here some practical guidelines for the oncologist to help in the clinical care of patients under ICB immunotherapy.


Thanks to their recent FDA and EMA approval, anti-CTLA-4 and anti-PD-1 immune checkpoint blockade (ICB) monoclonal antibodies are becoming parts of the oncologists' armamentarium against melanoma and non small-cell lung cancer (NSCLC). Beyond melanoma and NSCLC, ICBs are showing promising responses across many different cancer subtypes including small-cell lung cancer [15% objective response rate (ORR)],[1] renal cell carcinoma (25% ORR),[2] urothelial cancer (25% ORR),[3] head and neck squamous cell carcinoma (12%–25% ORR),[4,5] gastric cancer (20% ORR),[6] hepatocellular carcinoma (20% ORR),[7] ovarian cancer (15% ORR),[8–10] triple negative breast cancer (20% ORR),[11] mismatch repair deficient colorectal cancer (60% ORR)[12] and Hodgkin disease (65%–85% ORR).[13,14] Because these responses are durable and eventually impact the overall survival of patients, it can be already anticipated that many other indications will extend the current approvals. Therefore, ICBs have settled in the oncology arena for good and they will be prescribed in a large number and wide variety of cancers in a near future. As a consequence, the number of patients exposed to these new immunotherapies will also dramatically increase. ICBs generate atypical types of tumor responses[15] and have a specific toxicity profile which is challenging the historical oncologists' practices.[16] Indeed, the clinical management of immune-related adverse events (irAEs) is new to many oncologists. Most irAEs remain mild in intensity but ~10% of patients treated with anti-PD-1 ICBs will develop severe, sometimes life-threatening, grade 3–4 dysimmune toxicities.[17]

On the basis of our immunotherapy clinical practice and our experience in irAEs management together with our network of organs' specialists, we have built institutional guidelines for the clinical care of ICB-treated patients. In this manuscript, we aim at sharing with the oncology community the five pillars of Gustave Roussy cancer center immunotherapy toxicity management guidelines (Figure 1).

Figure 1.

The five pillars of immunotherapy toxicity management.