Research and practice in thrombosis and haemostasis · 2026
Antiphospholipid antibody formation during immune checkpoint inhibition in patients with cancer: a prospective cohort study.
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Strijdhorst Anniek, Salet Dorien M, Schoenaker Jente M, van der Vegte Vossa, Seijkens Tom T P, van Laarhoven Hanneke W M, Urbanus Rolf T, van Es Nick
Аннотация
BACKGROUND: Immune checkpoint inhibitors (ICIs) significantly improve survival in many cancer types. However, ICIs are associated with an increased risk of venous and arterial thromboembolism, and the underlying mechanisms are incompletely understood. We hypothesized that ICI therapy may induce the development of antiphospholipid antibodies, contributing to hypercoagulability.
OBJECTIVES: To evaluate changes in antiphospholipid antibody positivity and thrombin generation in patients with cancer initiating ICI therapy.
METHODS: Data were used from ITHACA, a prospective cohort study including adults with cancer who underwent blood sampling at baseline and 3 months after starting ICI therapy. At both time points, lupus anticoagulant, anti-β2-glycoprotein I immunoglobulin (Ig)G/IgM, anticardiolipin IgG/IgM, and thrombin generation were measured. The primary outcome was the development of antiphospholipid antibody positivity at 3 months. Secondary outcomes included changes in thrombin generation (endogenous thrombin potential and peak height) and thromboembolic events.
RESULTS: Forty patients initiating anti-programmed cell death protein 1 or anti-cytotoxic T-lymphocyte-associated antigen 4 therapy were included. The median age was 63 years (IQR, 57-69); 80% were male, and 5% were on anticoagulation. At baseline, 3 patients (8%) had positive anti-β2-glycoprotein I or anticardiolipin antibodies, compared with 2 patients (5%) at 3 months (P = 1.00). No patients had a positive lupus anticoagulant. Endogenous thrombin potential (935 vs 949 nM ∗ min; P = .65) and peak height (277 vs 279 nM; P = .49) were similar at both time points. One patient developed venous thromboembolism.
CONCLUSION: ICI therapy was not associated with the development of antiphospholipid antibodies or changes in thrombin generation after 3 months. These findings suggest that the short-term risk of thromboembolic events after initiation of ICI therapy may not be mediated by antiphospholipid antibodies.
OBJECTIVES: To evaluate changes in antiphospholipid antibody positivity and thrombin generation in patients with cancer initiating ICI therapy.
METHODS: Data were used from ITHACA, a prospective cohort study including adults with cancer who underwent blood sampling at baseline and 3 months after starting ICI therapy. At both time points, lupus anticoagulant, anti-β2-glycoprotein I immunoglobulin (Ig)G/IgM, anticardiolipin IgG/IgM, and thrombin generation were measured. The primary outcome was the development of antiphospholipid antibody positivity at 3 months. Secondary outcomes included changes in thrombin generation (endogenous thrombin potential and peak height) and thromboembolic events.
RESULTS: Forty patients initiating anti-programmed cell death protein 1 or anti-cytotoxic T-lymphocyte-associated antigen 4 therapy were included. The median age was 63 years (IQR, 57-69); 80% were male, and 5% were on anticoagulation. At baseline, 3 patients (8%) had positive anti-β2-glycoprotein I or anticardiolipin antibodies, compared with 2 patients (5%) at 3 months (P = 1.00). No patients had a positive lupus anticoagulant. Endogenous thrombin potential (935 vs 949 nM ∗ min; P = .65) and peak height (277 vs 279 nM; P = .49) were similar at both time points. One patient developed venous thromboembolism.
CONCLUSION: ICI therapy was not associated with the development of antiphospholipid antibodies or changes in thrombin generation after 3 months. These findings suggest that the short-term risk of thromboembolic events after initiation of ICI therapy may not be mediated by antiphospholipid antibodies.