J-M. Michot

Management of immune checkpoint blockade dysimmune toxicities: a collaborative position paper.

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 Roussys 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.

Letter to the EditorAllergic broncho-pulmonary aspergillosis following treatment with an anti-programmed cell death protein 1 monoclonal antibody therapy

a Thoracic Department, Marie Lannelongue Surgical Center, Le Plessis Robinson, 92350, France b Drug Development Department, Gustave Roussy Institute, Villejuif, 94805, France c APHP, Internal Medicine and Clinical Immunology Department, Bicêtre Hospital, AP-HP, Le Kremlin Bicêtre, 94270, France d Université Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin Bicêtre, France e Medical Oncology Department, Gustave Roussy Institute, Villejuif, 94805, France

Allergic broncho-pulmonary aspergillosis following treatment with an anti-programmed cell death protein 1 monoclonal antibody therapy

a Thoracic Department, Marie Lannelongue Surgical Center, Le Plessis Robinson, 92350, France b Drug Development Department, Gustave Roussy Institute, Villejuif, 94805, France c APHP, Internal Medicine and Clinical Immunology Department, Bicêtre Hospital, AP-HP, Le Kremlin Bicêtre, 94270, France d Université Paris Sud, 63 rue Gabriel Péri, 94276 Le Kremlin Bicêtre, France e Medical Oncology Department, Gustave Roussy Institute, Villejuif, 94805, France

P1.07Outcome of patients with relapsed/refractory lymphoma in a large cohort inside a phase 1 clinic department

ABSTRACT Background: Treating relapsed/refractory lymphoma remains a challenge. While phase 1 trials classically aim to determine the recommended phase 2 dose (RP2D), the search of anti-tumor activity is increasingly evaluated. We aimed to assess the tolerance and efficacy of phase 1 trial and to determine a simple scoring system to identify patients who will prematurely discontinue phase 1 studies (before six weeks), in a large cohort of patients with relapsed/refractory lymphoma. Patients and Methods: Data from 105 consecutive patients with relapsed/refractory lymphoma treated within a panel of 17 phase 1 trials were collected, between 2008 and 2014. At inclusion, median age was 66 years [range: 23-83]. Lymphoma histological patients types were: 58 (55%) aggressive non-Hodgkin lymphoma (34 diffuse large B-cell lymphoma, 7 T-cell lymphoma and 17 Mantle cell lymphoma), 31 (30%) indolent non-Hodgkin lymphoma and 16 (15%) Hodgkin lymphoma. The predefined Gustave Roussy (GR) score combined two simple variables, PS and baseline serum albumin (+1 if PS = 0, +1 if albumin ≤ 35g/l). Results: Grade 3 or 4 adverse events were experienced by 40/105 (38%) patients. With a median follow-up of 10 months, median OS and progression free survival (PFS) were respectively 19 (CI95%: 12-37) and 4 (CI95%: 2-5) months. Best overall response rate and disease control rate were 22% and 56%, respectively. Histological types analysis shown median OS was 10, 45 and 47 months in aggressive-NHL, Hodgkin and indolent-NHL, respectively (p 0, baseline albumin ≤ 35 g/l and baseline LDH ≥ 250 UI/L were significantly associated with poorer OS. Patients with a GR score = 0 experienced significantly better OS compared to patients with a score = 1 and a score = 2 (37 months vs 17 months vs 9 months; p = 0.007). A premature study discontinuation was recorded in 28/105 patients (27%). The GR score distinguishes patients most likely to remain on study for more than 6 weeks. Conclusion: The three parameters WHO performance status (PS) > 0, baseline albumin ≤ 35 g/l and baseline LDH ≥ 250 UI/L are associated with OS and premature withdrew of study. Both PFS and OS survival curves demonstrates a plateau, in favor of therapeutic effect potentially maintained.