Incidence of Vascular Thromboembolic Events in Patients Receiving Immunotherapy: A Single Institution Experience

Introduction:

Cancer is known to cause a hypercoagulable state predisposing to venous thromboembolism (VTE). In a retrospective study by Lyman et al., the incidence of VTE 3.5 months after starting chemotherapy was 7.3% rising to 13.5% at 12 months in a cohort of more than 27,000 patients. A two-fold increase in the incidence of deep venous thrombosis (DVT) and pulmonary embolism (PE) has also been reported in hospitalized cancer patients compared to non-cancer patients. Systemic cancer treatments are known to be associated with increased VTE risk but the incidence of vascular thromboembolic events with newer treatment modalities like immunotherapy has not been broadly investigated. This study aims to assess the incidence of vascular events including VTE, strokes and myocardial infarction in cancer patients receiving anti PD1/PDL1 therapy at a single institution.

Methods:

We retrospectively analyzed the data of 154 cancer patients over 18 years of ages, who were treated with anti PD-1/PDL-1 therapy at the University of Oklahoma from 2014 to 2016. We used descriptive statistics to describe the incidence of vascular thromboembolic events. Kaplan Meier Survival analysis was used to estimate the progression free survival (PFS) according to VTE occurrence.

Results:

The majority of patients were females (57%). The median age was 63 years (range 23-89). Median number of treatments received was 5 (range 1-30). Lung cancer was the most common diagnosis (20.8%) followed by melanoma (20.1%) and ovarian cancer (12.3%). 92% of patients had stage 4 cancer. Nivolumab was the most commonly used agent (47.4%) followed by Pembrolizumab (22.7%), other investigational agents (22.7%) and Atezolizumab (7.2%).

The median follow up time was 198 days (approximately 7 months). VTE occurred in 16/154 patients (10%). Nine patients had DVT, 6 patients had PE and 1 patient had DVT and PE. VTE was most common in patients with lung cancer (17%) and patients with ovarian cancer (17%). The occurrence of VTE was not significantly associated with a worse progression free survival [150 days versus 146 days for VTE occurrence vs no occurrence respectively (p = 0.725)]. No cases of stroke or myocardial infarction were recorded.

Conclusion:

The incidence of VTE in this cohort of cancer patients receiving immunotherapy appeared to be similar to the incidence previously reported with other systemic therapies. No arterial thromboembolic events were recorded in our study. Large multicenter studies are needed to derive definite conclusions.