Safety of immune checkpoint inhibitors in patients with cancer and pre-existing autoimmune disease

Abstract

Background: Patients with pre-existing autoimmune disease (AD) have been largely excluded from clinical trials of immune checkpoint inhibitors (ICI), so data on safety of ICIs among patients with pre-existing AD are relatively limited. There is a need for deeper understanding of the type and management of complications from ICI in patients with pre-existing AD. We sought to investigate the safety of ICIs in patients with pre-existing ADs as well as factors associated with AD flare.Methods: Consecutive patients with pre-existing AD who received monotherapy as well as combination of ICI therapies at our institution from September 2015 through September 1 st , 2018 were identified.Clinical information was abstracted via manual chart review. Clinical factors associated with AD flare were determined using multivariable logistic regression.Results: A total of 42 patients were identified of whom 12 developed AD flare. All flares were treated with oral or topical corticosteroids, while a patient with flare of rheumatoid arthritis was treated with tofacitinib and another patient with Crohn's flare was treated with infliximab. Female sex, smoking status, higher age at the start of ICI therapy, cancer type, such as melanoma and lung cancer as compared to other cancers, were not significantly associated with AD flare, however, patients with underlying rheumatologic AD were noted to have a five times greater likelihood of flare as compared to other non-rheumatologic AD. Nine patients developed new immune related adverse events (IRAEs) unrelated to underlying AD, such as inflammatory poly-arthropathy, neuropathy, hypothyroidism, diarrhea, lichenoid drug eruptions, which were managed with oral and/or topical corticosteroids. ICI was stopped in six patients due to AD flare, in four patients due to IRAE flare (out of which one resumed ICI after resolution of IRAE). Conclusions:In patients with pre-existing AD treated with ICI, AD flare occurred in 28% of patients and were managed successfully with corticosteroids alone or with additional disease-modifying therapies. ICI could be considered in patients with AD, but with very close monitoring and preemptive multidisciplinary collaboration.

Immunotherapy and Gene Therapy: New Challenges in the Diagnosis and Management of Drug-Induced Liver Injury

“…As concerns of preexisting autoimmune disease exacerbation and/or development of new immune-mediated side effects were major, all patients with an autoimmune disease, regardless of the organ, have been excluded from the clinical trials evaluating ICIs. Consequently, the majority of data available so far on the side effects of ICIs in patients already known with autoimmune disease come from case reports and retrospective studies ( Abdel–Wahab et al, 2018 ; Danlos et al, 2018 ; Kahler et al, 2018 ; Cortellini et al, 2019 ; Tison et al, 2019 ; Alexander et al, 2021 ; Hoa et al, 2021 ). In these works, preexisting autoimmune liver diseases are nearly completely absent.…”

“…In a global view, data available up to now describe a higher rate of irAEs (up to 75% of the patients) in patients with a past medical history of autoimmune disease ( Abdel-Wahab et al, 2018 ; Danlos et al, 2018 ; Kahler et al, 2018 ; Cortellini et al, 2019 ; Tison et al, 2019 ; Alexander et al, 2021 ; Hoa et al, 2021 ). Both de novo irAEs and exacerbation of the already known autoimmune disease were reported, independent of the degree of activity (active vs. inactive) of the preexisting disease; immunosuppressive drugs were rarely needed, neither ICI discontinuation.…”

Treatment Equity in the Immunotherapy Era: Options for Patients with Both Autoimmune Disease and GU Cancers

“…Patients with pre-existing autoimmune diseases have been excluded from immunotherapy based clinical trials, and pre-existing autoimmune diseases have been identified in a meta-analysis to be a risk factor for irAE incidence. As one may expect, based on several prospective and retrospective studies, there were higher irAEs in those with pre-existing autoimmune diseases compared to those without [48][49][50]. Table 2 includes several studies of patients with pre-existing autoimmune disease who had treatment with ICI.…”

“…Pembrolizumab (50), nivolumab A larger systemic meta-analysis characterized irAEs in patients with pre-existing autoimmune diseases. The incidence of pre-existing autoimmune disease flare was 35% and incidence of irAEs was 33%.…”

“…ICIs can frequently induce new irAEs as well as flares of existing autoimmune diseases. Studies seem to suggest that most patients experiencing flares or irAEs of an autoimmune syndrome can be mostly managed without discontinuation of ICI [ 9 , 50 ]. In addition, other observational studies with 524 patients found that about 6.6% of patients receiving ICIs were referred to rheumatology for irAEs.…”