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

Autor: Wallwork RS; Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States., Kotzin JJ; Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, United States., Cappelli LC; Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States., Mecoli C; Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States., Bingham CO 3rd; Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States., Wigley FM; Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States., Wilson PC; Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, United States., DiRenzo DD; Department of Medicine, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA, United States., Shah AA; Department of Medicine, Division of Rheumatology, Johns Hopkins School of Medicine, Baltimore, MD, United States. Electronic address: ami.shah@jhmi.edu.
Jazyk: angličtina
Zdroj: Seminars in arthritis and rheumatism [Semin Arthritis Rheum] 2024 Aug; Vol. 67, pp. 152460. Date of Electronic Publication: 2024 May 04.
DOI: 10.1016/j.semarthrit.2024.152460
Abstrakt: 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.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ami Shah reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health. Christopher Mecoli reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health. Laura Cappelli reports was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health. Rachel Wallwork reports financial support was provided by National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health. Rachel Wallwork reports financial support was provided by The Jerome L Greene Foundation. Ami Shah reports financial support was provided by The Donald B. and Dorothy L. Stabler Foundation. Rachel Wallwork reports financial support was provided by The Rheumatology Research Foundation. Clifton Bingham reports a relationship with Bristol Myers Squibb that includes: consulting or advisory and funding grants. Laura Cappelli reports a relationship with Bristol Myers Squibb that includes: consulting or advisory and funding grants. Laura Cappelli reports a relationship with Amgen that includes: consulting or advisory. Ami Shah reports a relationship with Kadmon Corporation that includes: funding grants. Ami Shah reports a relationship with Arena Pharmaceuticals that includes: funding grants. Ami Shah reports a relationship with Medpace LLC that includes: funding grants. Ami Shah reports a relationship with Eicos Sciences that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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