Background/Purpose: Immune checkpoint inhibitors (ICIs), by activating the immune system (specifically, T-cells), foster the reaction against tumor cells. However, parallelly, autoimmune phenomena, known as immune- related adverse effects (ir-AEs) (PMID 33902919, 29442540), can be triggered and manifest in any organ or tissue. The most common rheumatic manifestations are inflammatory arthritis, polymyalgia rheumatica, and myositis, but other inflammatory cases have also been described (PMID 32403289). More data on their frequency and characterization are needed.
Our objective was to prospectively evaluate the incidence of rheumatic ir-AEs during ICIs treatment, along with clinical characterization, management required, and outcomes.

Methods: An observational, prospective study was conducted at a tertiary center in Spain, led by the oncology department with the participation of several specialties, to evaluate the occurrence of ir-AEs in patients starting ICIs between January 2019 and April 2022. Participants were routinely followed at oncology clinics to detect ir-AEs through pre-specified clinical and laboratory assessments. For rheumatic symptoms, ir-AEs were studied by records review and evaluated in person at rheumatology clinics for those with a degree of involvement of ≥2, according to the ASCO guidelines (3). The incidence – with a 95% confidence interval (CI) – and characterization of defined rheumatic ir- AEs are presented here.

Results: Of 181 patients, 21 (11.6%, 95%CI 7.7-17.1%) developed rheumatic ir-AEs, 13 men (61.9%) with a median age of 62.3 years (p25-75 51.8-75.0). The median time from the start of ICIs to the development of rheumatic ir-AEs was 85 days (p25-75 51.5-165).The incidence rate was 0.92 cases per 100 patient-months. Blood tests for autoimmunity were positive in 69.2% of available cases (9/13), but all at a low titer (table). According to ASCO guidelines, most patients had a toxicity grade 1-2, but 3 (14.3%) patients presented with severe manifestations (grade 3): 1 (4.8%) case of inflammatory arthritis, 1 (4.8%) of xerostomia, and 1 (4.8%) of Raynaud’s phenomenon with ulcers. 9 (42.9%) patients also presented with concurrent ir-AEs of different types. Rheumatic ir-AEs were successfully settled, though infliximab and intravenous vasodilators were required for some cases. While discontinuing ICIs was mostly due to neoplasm progression (47.6%), in 3 cases (14.3%) it was due to grade-3 rheumatic manifestations. 7 (33.3%) patients died during follow-up due to the oncological disease, no case due to rheumatic toxicity.

Conclusion: In this prospective and multidisciplinary study, 11.6% of patients treated with ICIs developed rheumatic ir-AEs. We estimated an incidence rate of 0.92 cases per patient-month. The majority experienced mild or moderate involvements, although severe cases were also observed. Therefore, a coordinated approach with oncologists is essential for patients treated with ICIs who are at risk of developing rheumatic ir-AES.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/multidisciplinary-prospective-study-of-patients-treated-with-immune-checkpoint-inhibitors-who-developed-rheumatic-immune-related-adverse-events/