BOSTON — Retrospective studies suggest that receipt of immune checkpoint inhibitors (ICIs) may increase the risk of venous thromboembolism (VTE) compared to chemotherapy. Are the findings skewed by the severity of disease and prior exposure to multiple lines of therapy, or do ICIs independently increase the risk of dangerous clotting?
With the types of cancers treated by ICIs expanding, the number of patients receiving them continues to rise rapidly, increasing the urgency of understanding the risks associated with these targeted therapies. A national team of researchers including investigators at the VA Boston Healthcare System teased apart the possible confounding factors by examining the increase in risk of VTE in veterans receiving first-line ICIs in the first year after diagnosis compared to those receiving chemotherapy in the same time frame.
The study included patients with stage III or IV cancer of the lung, kidney, bladder, head/neck as well as hepatocellular carcinoma and melanoma. ICIs are also used to treat classic Hodgkin lymphoma and primary mediastinal B-cell lymphoma, but patients with these hematologic malignancies were not included in this analysis.
In a presentation at the 64th American Society of Hematology Annual Meeting in New Orleans on Dec. 11, they said that, of the 45,253 veterans who received care through the VA for the included cancers between 2016 and 2020, only 1,660 received ICIs in the first year following diagnosis as first-line therapy for FDA-approved cancers, and 6,489 veterans received chemotherapy and met the other criteria.1
The team matched the two groups by age, sex, race, year of diagnosis, VA frailty index, history of VTE, type and stage of cancer, time between diagnosis and treatment initiation, recent history of prolonged hospitalization, body mass index, hemoglobin, white blood cell count and platelet count. Despite this matching, significant differences between the groups persisted in age, year of diagnosis, cancer type and stage and time to treatment start, so the team used inverse probability weighting to balance all covariates so that standardized mean difference did not exceed 0.1.
The primary analysis found that 5.5% of the chemotherapy group and 6.1% of the ICI group experienced VTE within six months of treatment initiation (Weighted relative risk 1.10, 95% CI 0.8301.46). In a secondary analysis of patients with lung cancer that included a third group who received both ICI and chemotherapy, VTE occurred at six months in 5.83% of the chemotherapy only group. In comparison, VTE occurred in 6.13% of the ICI only group (RR 1.05, 95% CI: 0.62-1.68) and 8.13% of the ICI plus chemotherapy group (RR 1.39, 95% CI 0.93-2.07).
The team concluded that first-line ICI and chemotherapy had similar rates of VTE. While still nonsignificant, the 39% increase in risk for patients with lung cancer who received combination ICI and chemotherapy led the researchers to recommend additional investigation.
“Previous retrospective studies likely reported inflated rate of VTE in ICI due to indication bias,” they said. “Nonetheless, patients receiving ICI had a similar rate of VTE and should be risk stratified as those receiving chemo.”
- May SB, La J, Milner E, Riaz N, Amos CI, et al. Venous Thromboembolism Risk in Cancer Patients Receiving First-Line Immune Checkpoint Inhibitor Vs. Chemotherapy. Abstract 555. 2022 ASH Annual Meeting. Dec. 11, 2022.
