Immune checkpoint inhibitor therapy in patients with cancer and pre-existing systemic sclerosis

Rachel S Wallwork; Jonathan J Kotzin; Laura C Cappelli; Christopher Mecoli; Clifton O Bingham 3rd; Fredrick M Wigley; Parker C Wilson; Dana D DiRenzo; Ami A Shah

doi:10.1016/j.semarthrit.2024.152460

Immune checkpoint inhibitor therapy in patients with cancer and pre-existing systemic sclerosis

Semin Arthritis Rheum. 2024 May 4:67:152460. doi: 10.1016/j.semarthrit.2024.152460. Online ahead of print.

Authors

Rachel S Wallwork¹, Jonathan J Kotzin², Laura C Cappelli¹, Christopher Mecoli¹, Clifton O Bingham 3rd¹, Fredrick M Wigley¹, Parker C Wilson², Dana D DiRenzo², Ami A Shah³

Affiliations

¹ Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States.
² Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, United States.
³ Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: ami.shah@jhmi.edu.

PMID: 38733668
DOI: 10.1016/j.semarthrit.2024.152460

Abstract

Objective: Immune checkpoint inhibitor (ICI) therapies have dramatically improved outcomes in multiple cancers. ICI's mechanism of action involves immune system activation to augment anti-tumor immunity. Patients with pre-existing autoimmune diseases, such as systemic sclerosis (SSc), were excluded from initial ICI clinical trials due to concern that such immune system activation could precipitate an autoimmune disease flare or new, severe immune related adverse events (irAE). In the present study, we report our experience with ICIs in patients with pre-existing SSc.

Methods: Patients with SSc who received ICI therapy for cancer were identified from the Johns Hopkins Scleroderma Center Research Registry. Through chart review and prespecified definitions, we identified whether patients experienced worsening SSc activity or new irAEs. SSc disease activity worsening was pre-defined as an increase in modified Rodnan skin score (mRSS), new scleroderma renal crisis, progression of interstitial lung disease (ILD) on CT scan, increased Raynaud's phenomenon frequency or severity, new pulmonary hypertension, or myositis flare. IrAEs also included active inflammatory arthritis and dermatitis.

Results: Eight patients with SSc who received ICI therapy for cancer were included. Overall, SSc symptoms remained stable during and after ICI therapy. None of the patients with long-standing sine or limited cutaneous SSc (lcSSc) had progressive skin thickening after ICI therapy. One patient, who was early in his diffuse cutaneous SSc (dcSSc) disease course, experienced worsening skin thickening and renal crisis. Three patients (38 %) experienced a total of five irAEs (grade 2: diarrhea, mucositis and dermatitis; grade 3: pneumonitis, and grade 4: nephritis). The patient with grade 4 nephritis developed scleroderma renal crisis and immune checkpoint related nephritis simultaneously. There were no deaths due to irAEs.

Conclusion: In this study, ICI therapy was well tolerated in patients with longstanding, sine or lcSSc. IrAE were common but generally manageable. Patients with early, active SSc may be at greater risk from ICI therapy, but more research is needed.

Keywords: Cancer; Immune checkpoint inhibitors; Immune related adverse events; Systemic sclerosis.

Abstract

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