Background/Purpose: Immune checkpoint inhibitors (ICIs) have dramatically improved the prognosis for many cancers. The therapeutic effect of ICIs is based on their ability to release the brakes on lymphocyte activation. However, this brake release can cause immune-related adverse events (IrAEs) in up to 60-80% of cases. Few observations of ICI-induced large vessel vasculitis (LVV) have been reported. We aimed to describe the characteristics and outcomes of LVV occurring after or during ICI therapy.

Methods: We conducted a European, multicenter, retrospective study of patients who received at least one infusion of ICI and subsequently presented with LVV between March 2018 and January 2023. The diagnosis of giant cell arteritis (GCA) among LVV patients was based on the 2022 ACR/EULAR classification criteria. Remission was defined by the absence of manifestations attributable to active vasculitis and normal acute phase reactants.

Results: Nineteen patients were included (median age 70 (IQR 61-75) years). Previous history of PMR or GCA was noted in 4 (21%) patients. The two most common cancers treated with ICIs were melanoma (32%) and renal cell carcinoma (26%). Five (26%) patients received a combination of nivolumab and ipilimumab, 7 (37%) pembrolizumab, 6 (32%) nivolumab, and 1 (5%) atezolizumab. First LVV manifestations occurred after a median of 5 (IQR 3-19) ICI infusions and a median time of 4 (IQR 2-15) months since the first ICI infusion.

Six (32%) patients had cephalic manifestations, 6 (32%) had vascular manifestations, and 7 (37%) had both. Four patients (21%) had visual loss. Nine (47%) patients had PMR symptoms and 5 (26%) had other IrAEs, mainly hepatitis. 18F-FDG PET/CT showed hypermetabolism of the aorta or its main branches in 12 (63%) patients. Temporal artery biopsy was positive in 3/6 cases. Overall, 13 (68%) of patients fulfilled ACR/EULAR criteria for GCA.

ICIs were still being used at the onset of LVV in 16 patients, while they were discontinued prior to LVV in 3 patients. For patients still on ICIs, management consisted of definitive discontinuation of ICIs in 10 (53%) patients and temporary discontinuation or continuation of ICIs in 6 (32%) patients.

All patients received oral glucocorticoids. The median initial prednisone dose was 0.7 g/kg/d (IQR 0.7-1). Two (11%) patients received tocilizumab as first-line therapy.

Median follow-up after LVV diagnosis was 8 months (IQR 4-14). Remission was achieved in 18 (95%) patients. Three patients relapsed during prednisone tapering, at a median dose of 10 mg/d (IQR 5-15). Overall, 4 (21%) patients did not respond or relapsed during prednisone tapering, including 1/13 (8%) of patients who discontinued ICIs and 3/6 (50%) of patients who continued to receive ICIs. At the end of follow-up, 4/18 (22%) patients had died, 3 of cancer and 1 of acute coronary syndrome.

Conclusion: LVV is a rare IrAE that usually occurs early after the initiation of ICI. Unexplained elevations in acute phase reactants in ICI-treated patients should prompt clinicians to look for signs of LVV, as severe ischaemic manifestations such as visual loss may occur. Patients with ICI-induced LVV who were maintained on ICI or rechallenged had a more refractory or relapsing course.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/immune-checkpoint-inhibitors-induced-large-vessel-vasculitis-data-from-a-multicenter-study/