Antiphospholipid antibody formation during immune checkpoint inhibition in patients with cancer: a prospective cohort study
A Strijdhorst, D M Salet, J M Schoenaker, V Van Der Vegte, T T P Seijkens, H W M Van Laarhoven, R T Urbanus, N Van EsAbstract
Background
Immune checkpoint inhibitors (ICIs) significantly improved survival in many cancer types. However, ICIs are associated with increased risk of venous (VTE) and arterial thromboembolism (ATE), and the underlying mechanisms are incompletely understood. We hypothesized that ICI therapy may induce antiphospholipid antibody development, contributing to hypercoagulability.
Aim
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 (anti-β2GPI) IgG/IgM, anticardiolipin IgG/IgM, and thrombin generation were measured. Primary outcome was development of antiphospholipid antibody positivity at 3 months. Secondary outcomes included changes in thrombin generation (endogenous thrombin potential (ETP) and peak height) and thromboembolic events.
Results
Forty patients initiating anti-PD-1 or anti-CTLA-4 therapy were included. Median age was 63 (interquartile range (IQR), 57-69), 80% were male, 5% used anticoagulation (Table 1). At baseline, three patients (8%) had positive anti-β2GPI or anticardiolipin antibodies versus two patients (5%) at 3 months (P=1.00). No patients had a positive lupus anticoagulant. ETP (935 vs 949 nM*min, P=0.65) and peak height (277 vs 279 nM, P=0.49) were similar at both timepoints (Figure 1). One patient developed VTE.
Conclusion
ICI therapy was not associated with 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.