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Significance of Immune-related Lipase Increase Induced by Antiprogrammed Death-1 or Death Ligand-1 Antibodies: A Brief Communication

Michot, Jean-Marie*,†; Ragou, Parvady*; Carbonnel, Franck‡,§; Champiat, Stéphane*,§; Voisin, Anne-Laure; Mateus, Christine; Lambotte, Olivier†,‡,#,**; Annereau, Maxime††

doi: 10.1097/CJI.0000000000000202
Clinical Studies

Antiprogrammed death-1 (anti-PD1) and antiprogrammed death ligand-1 (anti-PD-L1) antibodies are effective checkpoint inhibitors that stimulate the immune system against many types of cancers. The flip side of these immunotherapies is the generation of immune-related adverse events, which can theoretically affect all organs. Among these side effects, lipase increase is frequently observed; however the meaning of this biological abnormality remains poorly understood. We investigate in this case study all the lipase increases greater or equal to grade 2 that occurred in patients receiving anti-PD-1 or anti-PD-L1 treatments, to determine their biological and clinical significance. Twenty-one patients were retained with lipase increase related to the immune checkpoint inhibitor. Most of them (71%) were treated for a metastatic melanoma. The peak of lipase increase was observed at a median of 2.8 (range, 0.4–11.4) months after the initiation of the anti-PD1 or anti-PD-L1 treatment, which correlates with cycle 5 of treatment. Three of 21 patients (14%) had a clinical or radiologic immune-related pancreatitis that led to a permanent discontinuation of the treatment. In 15 of 21 (71%) patients, the lipase increase was not considered as clinically significant, and the treatment was continued without complications. The 3 remaining patients discontinued the treatment for progressive disease. These data indicate that lipase increase related to anti-PD1 or anti-PD-L1 is not associated with a significant clinical event in most cases. On the basis of these data, we propose that lipase increase in an asymptomatic patient and without radiographic abnormalities of the pancreas can be reasonably regarded as a not clinically significant event, allowing the continuation of the anti-PD-1 or anti-PD-L1 treatment.

*Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay

Unité de Pharmacovigilance, Gustave Roussy, Université Paris-Saclay

Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay

††Département de Pharmacie des Anticancéreux, Gustave Roussy, Université Paris-Saclay, Villejuif

Service de Médecine Interne et Immunologie clinique, Assistance Publique—Hôpitaux de Paris, Hôpital Bicêtre

Service de Gastroentérologie, Assistance Publique—Hôpitaux de Paris, Hôpital Bicêtre

§Université Paris Sud

**INSERM, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre

#Commissariat á l’Energie Atomique, Institut des maladies émergentes et des thérapies innovantes, Infectious Diseases Models for Innovative Therapies, Fontenay-aux-Roses, France

Reprints: Jean-Marie Michot, Département des Innovations Thérapeutiques et Essais Précoces, Gustave Roussy, Université Paris-Saclay, 114 rue Edouard Vaillant, Villejuif, F-94805, France. (e-mail:

Received July 4, 2017

Accepted September 22, 2017

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.