Op0278 musculoskeletal immune-related adverse events in 927 patients treated with immune checkpoint inhibitors for solid cancer

BackgroundThe prevalence of the musculoskeletal immune-related adverse events (irAEs) is probably underestimated, as most studies report only severe side effects. The largest prospective study with systematic monitoring by a rheumatologist, for musculoskeletal irAEs, concerned 35 patients.ObjectivesThe main objective was to describe each type of musculoskeletal irAEs: prevalence, clinical features, treatment regimen, ICI drug, time of occurrence and management of musculoskeletal irAEs. The secondary objectives were to describe IrAEs’course ant to investigated tumor response at 3 months after introduction of ICI according to IrAEs’grade, clinical features, pain patterns and the treatments used to manage musculoskeletal irAEs.MethodsWe conducted a retrospective study among patients who received ICI from 07/27/2014 to 05/08/2020 at the medical oncology department of the Institut Paoli-Calmettes, Marseille, France. All medical files were systemically reviewed by a rheumatologist who collected clinical features, time of occurrence, treatment regimen, irAEs management, course, outcomes and tumor response 3 months after introduction of ICI.ResultsIn our cohort of 927 patients treated with ICI for a solid tumor, 118 patients (12.7%) presented a musculoskeletal irAE. Their median age was 66.5, 61% were male, and they mainly had a lung (57.6%) or urological cancer (27.1%). The most frequently involved ICI was an anti PD-1. Arthralgias and myalgias were the most frequent musculoskeletal irAEs (76.3%) and inflammatory rheumatic features were reported in 36 patients (30.5%) with elevated acute phase reactants and negative immunological markers. The median time of onset was 2 months (IC 95% 1.8; 2.7). Musculoskeletal irAEs were mainly mild and no deaths were related. Painkillers were the most widely used treatments (86.4%). Systemic corticosteroids were used in 38 patients (32.2%) with a mean dose of 43 ± 35 milligrams/day. Among the inflammatory rheumatic features, 20 (55.5%) were treated with systemic corticosteroids and 8 with csDMARDs (16.7%). bDMARDs were not used in our cohort. Musculoskeletal irAEs resulted in discontinuation of the responsible ICI in 23 patients (19.5%). The majority of musculoskeletal irAEs (79.7%) resolved within a median time of 3 months (IC 95% 2.2;4.0). Tumor response at 3 months did not differ according to musculo-skeletal irAE severity, type of manifestation (arthralgias/myalgias versus inflammatory rheumatic features), pain patterns (mechanical versus inflammatory) or irAE treatments.ConclusionOur single-center cohort is the largest to our knowledge to describe all musculoskeletal irAEs in patients treated with ICI without focusing on severe or inflammatory manifestations. These musculoskeletal irAEs are frequent, mostly mild and well tolerated, resolving and allowing possible continuation of ICI treatment. Collaboration between oncologists and rheumatologists should be further encouraged to determine whether all musculoskeletal irAEs, even non-severe and non-inflammatory ones, are associated with a good tumor response to ICI.References[1]Kostine M and al, Rheumatology. 2019 Dec 1.[2]Belkhir R and al, Ann Rheum Dis. 2017 Oct.[3]Angelopoulou F and al, Rheumatol Int. 2021 Jan.[4]Kostine M and al, Ann Rheum Dis. 2021 Jan.[5]Cappelli LC and al, Arthritis Care Res. 2017 Nov.[6]Kostine M and al, Ann Rheum Dis. 2018 Mar.[7]Liew DFL and al, Int J Rheum Dis. 2019 Feb.[8]Cappelli LC and al, Seminars in Arthritis and Rheumatism. 2018 Dec.AcknowledgementsWe gratefully thank Patrick SFUMATO and Christophe ZEMMOUR (biostatisticians, Institut Paoli-Calmettes, Marseille), Doctor Frédéric BENIZRI (pharmacist, Institut Paoli-Calmettes, Marseille), Doctor Marie-Caroline GUZIAN (rheumatologist, Montélimar).Disclosure of InterestsNone declared