Safety and efficacy of immune checkpoint inhibitors in advanced urological cancers with pre-existing autoimmune disorders: a retrospective international multicenter study

Abstract

BackgroundThere is limited experience regarding the safety and efficacy of checkpoint inhibitors (CPI) in patients with autoimmune disorders (AD) and advanced urological cancers as they are generally excluded from clinical trials due to risk of exacerbations.MethodsThis multicenter retrospective cohort analysis of patients with advanced renal cell cancer (RCC) and urothelial cancer (UC) with pre-existing AD treated with CPI catalogued the incidence of AD exacerbations, new immune-related adverse events (irAEs) and clinical outcomes. Competing risk models estimated cumulative incidences of exacerbations and new irAEs at 3 and 6 months.ResultsOf 106 patients with AD (58 RCC, 48 UC) from 10 centers, 35 (33%) had grade 1/2 clinically active AD of whom 10 (9%) required corticosteroids or immunomodulators at baseline. Exacerbations of pre-existing AD occurred in 38 (36%) patients with 17 (45%) requiring corticosteroids and 6 (16%) discontinuing CPI. New onset irAEs occurred in 40 (38%) patients with 22 (55%) requiring corticosteroids and 8 (20%) discontinuing CPI. Grade 3/4 events occurred in 6 (16%) of exacerbations and 13 (33%) of new irAEs. No treatment-related deaths occurred. Median follow-up was 15 months. For RCC, objective response rate (ORR) was 31% (95% CI 20% to 45%), median time to treatment failure (TTF) was 7 months (95% CI 4 to 10) and 12-month overall survival (OS) was 78% (95% CI 63% to 87%). For UC, ORR was 40% (95% CI 26% to 55%), median TTF was 5.0 months (95% CI 2.3 to 9.0) and 12-month OS was 63% (95% CI 47% to 76%).ConclusionsPatients with RCC and UC with well-controlled AD can benefit from CPI with manageable toxicities that are consistent with what is expected of a non-AD population. Prospective study is warranted to comprehensively evaluate the benefits and safety of CPI in patients with AD.

The Efficacy and Safety of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease

“…On the aspect of safety, Menzies et al ( 15 ) reported that flares occurred more often in patients with active AID than in those with inactive AID (60% versus 30%, p = 0.039), and there was a trend for more flares in patients on immunosuppression treatment than in those not on immunosuppression (50% versus 31%, p > 0.05). The study of Martinez Chanza et al ( 33 ) also reached a conclusion consistent with that of Menzies et al. Similarly, the study of Leonardi et al ( 31 ) suggested that AID was more likely to flare in patients with active symptoms, and Kähler et al ( 26 ) also reported that flares occurred more often in patients on immunosuppression at the start of treatment.…”

“…Therefore, patients with those AIDs may be under-represented in the retrospective studies. Many studies yielded similar conclusions ( 15 , 26 – 29 , 31 , 33 – 36 , 38 ). That is, preexisting rheumatologic AIDs (such as RA, polymyalgia rheumatica) and Ps were most likely to effect AID flare after ICI therapy (the incidences of AID flare were 50% to 68% and 20% to 67% in patients with rheumatologic AIDs and Ps, respectively).…”

“…The most common preexisting AIDs were psoriasis (Ps, n = 39), thyroiditis (n = 30), and RA (n = 16). In the studies reported by Martinez Chanza et al ( 33 ), the rates of AID flare and newly developed irAEs were as high as 36% and 38%, respectively. However, TirAEs in the above two studies (58% and 46%, respectively) were generally mild and reversible, especially in patients with asymptomatic or mildly symptomatic AID, and the efficacy was similar in AID and non-AID patients.…”

“…There were 141 patients with urological cancers and AID in the studies reported by Martinez Chanza et al ( 33 ) and Loriot et al. ( 32 ).…”

“…The meta-analysis of Xie et al ( 52 ) reported that the pooled incidence of AID flare and newly developed irAEs were 35% and 33%, respectively, and there was no statistical difference between patients with and without immunosuppressive therapy regarding AID flare. Besides, almost all AID flares occurred at the beginning of ICI therapy—2 weeks to 1 year after initiation, but mostly around 1–2 months ( 15 , 27 , 29 , 31 , 33 , 41 ). Most AID flares had similar manifestations and affected the same anatomic sites as prior AID symptoms ( 27 , 31 , 36 ).…”