Thrombosis and Intracranial Hemorrhage in Patients with Metastatic Brain Cancer Treated with Immune Checkpoint Inhibitors Versus Chemotherapy

Background Metastatic brain cancer increases the risk of thrombosis and intracranial hemorrhage (ICH). Immune Checkpoint Inhibitors (ICI) have emerged as breakthrough therapies for the treatment of metastatic disease. Thrombosis has been increasingly reported as a potential adverse event associated to ICI treatment. There is conflicting evidence on the comparative risk of thrombosis between ICI and chemotherapy, and limited data on bleeding outcomes during ICI treatment. We aimed to compare the rate of thrombosis and ICH in patients with metastatic brain tumors treated with ICI versus chemotherapy. Methods A retrospective, single-center cohort study was performed at Beth Israel Deaconess Medical Center. Patients with metastatic brain tumors, treated from 2010 to 2020 with ICI or chemotherapy were included. Primary endpoints included development of thrombotic and ICH events within 12 months of starting treatment. Thrombotic events included venous thromboembolism (VTE), or arterial thrombosis confirmed by imaging. ICH events were classified by a neuro-oncologist blinded to patient information. Intracranial bleeding due to surgical interventions or radiation therapy were excluded. Primary exposure was treatment group, defined as ICI with or without chemotherapy compared to chemotherapy alone. Proportions were compared using Chi square or Fisher's exact tests. Log-binomial regression was used to estimate relative risk (RR) and 95% confidence interval (CI) associated with each additional point of the Khorana score (KS). Cox hazard models were used to calculate the hazard of thrombosis and ICH in each group, accounting for death as a competing risk. Models were weighted by the inverse probability of treatment, estimated using age, gender, cancer, KS, elevated creatinine, and prior exposure to anticoagulants and/or antiplatelets (AC/AP) as covariates; weighting (IPTW) to calculate the cumulative incidence (CumI) of thrombosis and ICH among treatment groups, and stratified by use of AC/AP at the start of treatment. Results We included 264 patients with a median age of 65.4 years (Table 1). Overall, 59.8% were female. Major primary malignancies included non-small cell lung cancer (NSCLC) 189 (71.6%), SCLC 31 (11.7%), melanoma 13 (4.9%), and renal cell carcinoma 13 (2.9%). Regarding treatment, 78 (29.5%) patients received ICI, and 186 (70.5) chemotherapy; within the ICI group, 65.4% of patients also received chemotherapy. Overall, 28 patients developed thrombotic ev