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.
Checkpoint inhibitors (CPIs) have become standard of care for multiple types of malignancies and while end-stage renal disease is not a contraindication, these patients are frequently excluded from clinical trials. As a result, there is limited data regarding the safety and efficacy of CPI use in this patient population. In this case series, we report outcomes and adverse events in 8 patients on hemodialysis treated with CPIs. Treatment was overall well-tolerated with adverse events in 3 of 8 (37.5%) patients, with 1 (12.5%) having a grade 4 adverse event, which is comparable to the rate reported in literature for the overall population receiving CPI. No treatment related deaths were seen. Because of small sample size, efficacy data is limited. Further studies are needed in this patient population to elucidate the true incidence of adverse events and antitumor activity.
Cancer treatment has changed dramatically with the development of oral targeted therapies. Pazopanib, an oral VEGF tyrosine kinase inhibitor, is currently approved for advanced renal cell carcinoma, advanced soft tissue sarcoma, and is being studied for various tumor types. Due to the potential of increased exposure to pazopanib when crushed, pazopanib should be given as an intact whole tablet. Thus, in patients with difficulty swallowing medications or feeding tubes, pazopanib is usually not considered to be an option. Here, we describe two cases which show the administration of crushed pazopanib was feasible and had apparent clinical activity.
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