LOUIS—While VA research presented at the 64th American Society of Hematology Annual Meeting in New Orleans today indicated that concerns appear unfounded about venous thromboembolism (VTE) in patients using immune checkpoint inhibitors (ICI) to treat advanced or metastatic cancers in the first-line setting, the investigators called for additional studies to further probe a possible signal of a link to VTE in some patients with lung cancer who receive both ICI and chemotherapy.
A team led by Kristen Sanfilippo, MD, of the St. Louis VAMC, was already digging deeper into reports of elevated risk of serious clots in patients with lung cancer. San Filippo presented that team’s study results a day earlier.1
The St. Louis VA investigators and colleagues at the Fred Hutchison Cancer Institute in Seattle sought to identify specific risk factors that predispose patients to ICI-associated VTE and could be used to stratify outpatients with non-small cell lung cancer (NSCLC) for thromboprophylaxis. In addition to some indications that patients with lung cancer have a particularly elevated risk of VTE when receiving ICIs, NSCLC is also a common type of cancer that offered several years of data during which ICI therapies were frequently used.
The team identified 1,457 eligible veterans who were diagnosed with NSCLC between 2015 and 2019, received ICI therapy, and did not have a history of VTE with a prescription for an anticoagulant in the six months before they began ICI therapy. A new VTE event was defined as one that started 72 hours or more after initiation of ICI and occurred within the following six months. Superficial VTEs were excluded.
Of the 1,457 veterans in the study, 1,073 received a single ICI and 11 received two ICI therapies simultaneously. Another 373 received an ICI and chemotherapy combination. Median age was 69 and 96% of the veterans were male, while 80.1% were white.
Overall, 77 patients, or 5.3% of the population experienced a VTE within the six month period. Of those, 27 received ICI plus chemotherapy and 50 ICI alone. Pulmonary embolisms accounted for 44% of the events, while pulmonary embolism (PE) plus deep vein thrombosis (DVT) occurred in 10%. An additional eight veterans had proximal DVT and one patient had distal DVT. Fourteen veterans (18%) developed an unspecified lower extremity DVT and another four (4%) were unclassified.
More than 7% of patients (105) had a history of VTE prior to starting ICI therapy but were not taking an anticoagulant. Of the 102 patients on a direct oral anticoagulant or warfarin at the start of ICI, seven developed VTE, though further analysis determined that four had stopped taking anticoagulants at the time of their VTE event.
During the six-month follow-up period, 63.6% of patients died. Of those who developed VTE, 83.1% died.
Multivariable modeling of competing risks revealed two independent risk factors for VTE. Combination ICI/chemotherapy increased the risk by 75% (HR 1.75, 95% CI:1.07-2.83). A history of VTE more than six months before ICI initiation increased risk nearly fivefold (HR 4.81, 95% CI: 2.6-8.9). Race and comorbidities did not emerge as risk factors and Khorana Score did not increase VTE risk in a statistically significant way.
Based on their findings and the growing diversity of cancer therapies, the team said that “modifications to available VTE risk assessment models could improve personalized thromboprophylaxis strategies to decrease the risk of cancer-related VTE in high-risk populations.” They noted that such a model is under development.
- Sanfilippo KM, Luo S, Lyman GH, Calverley DC, Kuderer NMM. Identification of Risk Factors for and Development of a Predictive Model for Immunotherapy-Associated Venous Thromboembolism (VTE) in Patients with Non-Small Cell Lung Cancer. Abstract 1190. 2022 ASH Annual Meeting. Dec. 10, 2022.