Capucine Baldini1, Patricia Martin Romano2, Anne-Laure Voisin3, François-Xavier Danlos2, Stéphane Champiat2, Salim Laghouati3, Maria Kfoury2, Hélène Vincent4, Sophie Postel-Vinay2, Andreea Varga2, Perrine Vuagnat2, Vincent Ribrag2, Laura Mezquita4, Benjamin Besse4, Antoine Hollebecque2, Olivier Lambotte5, Jean-Marie Michot2, Jean-Charles Soria6, Christophe Massard2, Aurélien Marabelle7. 1. Gustave Roussy, Université Paris-Saclay, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France. Electronic address: capucine.baldini@gustaveroussy.fr. 2. Gustave Roussy, Université Paris-Saclay, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France. 3. Gustave Roussy, Université Paris-Saclay, Unité de Pharmacovigilance, Villejuif, France. 4. Gustave Roussy, Université Paris-Saclay, Département d'Oncologie Médicale, Villejuif, France. 5. Assistance Publique Hopitaux de Paris (AP-HP), Centre Hospitalier et Universitaire Kremlin Bicêtre, Médecine Interne, Kremlin Bicêtre, France; Université Paris Saclay, France; Université Paris-Sud, Orsay, France. 6. Université Paris-Sud, Orsay, France. 7. Gustave Roussy, Université Paris-Saclay, Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Villejuif, France; INSERM U1015, Gustave Roussy, Villejuif, France.
Abstract
BACKGROUND: Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts. METHODS: Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method. RESULTS: Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups. CONCLUSION: Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs.
BACKGROUND: Aging is an important risk factor for cancers and is associated with poor prognosis. Weakness of the immune system, also called immunosenescence may occur with older age. The impact of aging on efficacy and safety of immune checkpoint blockers, such as anti-programmed death (ligand) PD-(L)1, remains undetermined. This study aims to evaluate the incidence of immune-related adverse events (irAEs) in patients aged 70 years or older than their younger counterparts. METHODS:Patients with advanced solid tumors treated at Gustave Roussy with an anti-PD-(L)1 monotherapy between June 2014 and October 2017 were prospectively included within the dedicated irAEs pharmacovigilance registry REISAMIC (Registre des Effets Indésirables Sévères des Anticorps Monoclonaux Immunomodulateurs en Cancérologie). The incidence of irAEs of grade ≥II was compared between patients aged ≥70 (old patients, OP) versus patients aged < 70 years (young patients, YP) using a chi-squared test. Survivals were estimated using the Kaplan-Meier method. RESULTS: Among the 603 patients treated by anti-PD(L)1, 191 were ≥70 y.o (OP) and 424 < 70 y.o (YP). The median (range) age of OP and YP were respectively 77 (70-93) and 59 years old (17-69). A total of 165 irAEs occurred in these patients (103 grade II and 58 grade III-IV). The overall incidence of grade ≥II irAEs was higher in OP than in YP (33% versus 25%, p = 0.03). In addition, OP were more prone of having multiples irAEs compared with YP (p = 0.037). Skin toxicities were more frequent in OP than in YP (p = 0.007) but endocrine toxicities were less frequent in OP than in YP (p = 0.044). This higher level of irAEs seems to be responsible for a higher rate of treatment discontinuation in OP (p = 0.2). There was no statistical difference in median time to toxicity, exposure to steroids or survival between the two groups. CONCLUSION: Although anti-PD-(L)1 immunotherapies remain an acceptable treatment option for older patients, prescribers should be aware that irAEs are more frequent in the elderly. Further translational studies are warranted to better understand the relationship between aging and irAEs.
Authors: Gino Kim In; Aparna Nallagangula; Jacob Seung Choi; Lisa Tachiki; Matthew J Blackburn; Stephen Capone; Kathryn B Bollin; Daniel Y Reuben; Keisuke Shirai; Sandy Zhang-Nunes; Omar Ragab; Alicia Terando; Jenny C Hu; Han Lee; Shailender Bhatia; Sunandana Chandra; Jose Lutzky; Geoffrey Thomas Gibney Journal: J Immunother Cancer Date: 2022-05 Impact factor: 12.469