Risk of Venous Thromboembolism in Patients with Lung Cancer Treated with Immune Checkpoint Inhibitors

Background: Thromboembolism (TE) in cancer significantly contributes to morbidity and mortality. Cancer immunotherapy is linked to several inflammatory immune mediated adverse events. Inflammation plays a key role in thrombosis but the association between immunotherapy and venous thromboembolism (VTE) has not been thoroughly investigated. Here, we report the incidence of thromboembolism in patients with lung cancer treated with immune checkpoint inhibitors (ICIs).

Methods: A single institution retrospective cohort of 514 adult patients with lung cancer who received ICIs (pembrolizumab, nivolumab, atezolizumab, ipilumab, avelumab) between 2013 and 2017 was included. Diagnosis of VTE (deep vein thrombosis and/or pulmonary embolism, and visceral vein thrombosis "VVT") was confirmed by imaging. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Cumulative incidence rate of VTE was estimated and compared using Gray's method.

Results: Of 514 patients (pts), 58.75% were males, 83.27% were white with a median age of 67 (range 22-91). Nivolumab was most commonly used (52.14%), followed by Pembrolizumab (30.16%), Atezolizumab (10.89%), combination of ipilimumab plus nivolumab (6.61), ipilimumab (2.33%), Avelumab (1.17%). 88.52% had stage 4 disease at treatment initiation. VTE events occurred in 62 pts (12%) (3.5% DVT, 4.47% PE, 2.72% both, 0.97 VVT, 0.19 VVT + PE, 0.19% VVT+DVT+PE). The cumulative incidence rate of VTE of all pts at 6-month and 1-year post IO was 7.6% (95% CI:5.3-9.9%) and 11.6% (95% CI:8.7-14.6%) respectively. The rate of survival without VTE at 6 months after IO treatment was 91% (95% CI: 89-94%). None of the following factors (age, gender, race, cancer staging, IO type or line) were significantly associated with time-to-VTE (TTVTE) survival post treatment (P >0.05). Median OS of all pts was 12.6 months (95% CI: 11.0-16.7 months), with 2-year OS rate of 35% (95% CI: 31-41%).

Conclusion: ICIs in lung cancer are associated with higher VTE risk within six months and a year of initiation of treatment. Further studies are needed to investigate the risk factors for ICIs-associated VTE.