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.

Purpose: Classical Hodgkin lymphoma (HL) frequently exhibits genetic alterations leading to overexpression of the programmed death-1 (PD-1) ligands, suggesting a possible vulnerability to PD-1 blockade. The phase Ib study KEYNOTE-013 (NCT01953692) tested the safety and efficacy of the anti–PD-1 antibody pembrolizumab in patients with hematologic malignancies. Based on its genetics, HL was included as an independent cohort. Methods: We enrolled patients with relapsed or refractory HL whose disease progressed on or after treatment with brentuximab vedotin. Patients received pembrolizumab, 10 mg/kg every 2 weeks, until disease progression occurred. Response to treatment was assessed at week 12 and every 8 weeks thereafter. Principal end points were safety and complete remission (CR) rate. Results: Thirty-one patients were enrolled; 55% had more than four lines of prior therapy, and 71% had relapsed after autologous stem cell transplantation. Five patients (16%) experienced grade 3 drug-related adverse events (AEs); there were no grade 4 AEs or deaths related to treatment. The CR rate was 16% (90% CI, 7% to 31%). In addition, 48% of patients achieved a partial remission, for an overall response rate of 65% (90% CI, 48% to 79%). Most of the responses (70%) lasted longer than 24 weeks (range, 0.14+ to 74+ weeks), with a median follow-up of 17 months. The progression-free survival rate was 69% at 24 weeks and 46% at 52 weeks. Biomarker analyses demonstrated a high prevalence of PD-L1 and PD-L2 expression, treatment-induced expansion of T cells and natural killer cells, and activation of interferon-γ, T-cell receptor, and expanded immune-related signaling pathways. Conclusions: Pembrolizumab was associated with a favorable safety profile. Pembrolizumab treatment induced favorable responses in a heavily pretreated patient cohort, justifying further studies.

Immunotherapy is becoming a standard of care for many cancers. Immune-checkpoint inhibitors (ICI) can generate immune-related adverse events. Interstitial lung disease (ILD) has been identified as a rare but potentially severe event.Between December 2015 and April 2016, we conducted a retrospective study in centres experienced in ICI use. We report the main features of ICI–ILD with a focus on clinical presentation, radiological patterns and therapeutic strategies.We identified 64 (3.5%) out of 1826 cancer patients with ICI–ILD. Patients mainly received programmed cell death-1 inhibitors. ILD usually occurred in males, and former or current smokers, with a median age of 59 years. We observed 65.6% grade 2/3 severity, 9.4% grade 4 severity and 9.4% fatal ILD. The median (range) time from initiation of immunotherapy to ILD was 2.3 (0.2−27.4) months. Onset tended to occur earlier in lung cancerversusmelanoma: median 2.1 and 5.2 months, respectively (p=0.02). Ground-glass opacities (81.3%) were the predominant lesions, followed by consolidations (53.1%). Organising pneumonia (23.4%) and hypersensitivity pneumonitis (15.6%) were the most common patterns. Overall survival at 6 months was 58.1% (95% CI 37.7–73.8%).ICI–ILD often occurs early and displays suggestive radiological features. As there is no clearly identified risk factor, oncologists need to diagnose and adequately treat this adverse event.