Venous thromboembolism incidence and risk assessment in lung cancer patients treated with immune checkpoint inhibitors

Abstract

Background: There are scarce data on venous thromboembolism (VTE) rates among non-small cell lung cancer (NSCLC) patients treated with immune-checkpoint inhibitors (ICI). The Khorana Score (KS), used to guide thromboprophylaxis in cancer patients, was validated in patients receiving chemotherapy.Objective: To assess VTE rates and KS performance among NSCLC patients treated with ICI or chemotherapy. Methods:We performed a retrospective cohort study of NSCLC patients starting either ICI or platinum-based chemotherapy. The 6-month cumulative incidence of VTE in the ICI and chemotherapy cohorts and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, using death as a competing risk. Subgroup analysis of low (0-1) and high (≥2) KS risk groups was performed. Results:The study included 345 NSCLC patients receiving single agent ICI (n = 176) or chemotherapy (n = 169). The 6-month cumulative incidence of VTE was 7.1% in the chemotherapy cohort and 4.5% in the ICI cohort (HR for chemotherapy = 1.6, 95% CI 0.66-3.9). Among chemotherapy treated patients, the high-risk KS group had a trend toward a higher VTE incidence, compared with patients with a low-risk KS (HR 3.04, 95% CI 0.82-11.22). Among ICI-treated patients, the high-risk KS group had a trend toward a lower VTE incidence compared with the low-risk group (HR 0.17, 95% CI 0.02-1.36). Conclusions: VTE rates were higher among NSCLC patients treated with platinumbased chemotherapy than those treated with ICI alone, though the precision of the relative estimate is low. The KS did not identify high-risk ICI-treated patients, suggesting that an ICI-specific risk model is warranted.

Hematologic complications of immune checkpoint inhibitors

“…Further evidence against the conclusion that ICIs are a clinically significant risk factor for cancer-associated VTE is presented in a retrospective analysis demonstrating that VTE occurred led frequently among lung cancer patients receiving an ICI than among those getting platinum-based chemotherapy. 25 It appears that, except for HLH (see below), PD-1, PD-L1 and CTLA-4 inhibitors are associated with hematological irAEs of similar rates, types, magnitudes and clinical courses. Because they are so infrequent, irAEs' predisposing factors, clinical presentations, mechanisms-of-toxicity, and management are uncertain.…”

Thrombotic Complications Associated with Immune Checkpoint Inhibitors

“…The references in the relevant articles were also manually searched for related studies. Overall, 18 retrospective studies reporting incidences and/or outcomes of venous and/or arterial thrombosis in patients on ICIs [ 1 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ] and 4 additional relevant systematic reviews and meta-analyses [ 24 , 25 , 26 , 27 ] were identified and included in this review.…”

“…Similarly, a Danish population cohort study showed a 6-month cumulative incidence of VTE of 4.1% (95% CI 2.3–6.7%) in patients receiving ICIs, comparable to 3.5% (95% CI 3.4–3.6%) found in those receiving chemotherapy [ 1 ]. In another study, Icht et al included 345 patients with NSCLC and reported a 6-month cumulative incidence of VTE of 7.1% in the chemotherapy cohort, compared with 4.5% in the ICI cohort (HR 1.6, 95% CI 0.6–3.9) [ 17 ]. However, as expected, the two cohorts were significantly different in baseline characteristics, including more metastatic disease and much less use as first-line therapy in the ICI cohort, which could have affected the results.…”

“…The Khorana score was derived in a patient population starting a new line of chemotherapy, and whether it can be applied to patients on ICIs is not fully understood. Most studies that investigated the Khorana score for its prediction performance in patients receiving ICIs have not found it to be predictive [ 11 , 16 , 17 , 18 , 20 ]. This indicates that patients on ICIs likely have different sets of risk factors compared to those on chemotherapy, and a specific risk assessment model in this population may be needed.…”

Risk Factors, Incidence, and Prognosis of Thromboembolism in Cancer Patients Treated With Immune Checkpoint Inhibitors

“…According to the score, patients are assigned into low-, medium-, and high-risk groups. However, almost all current relevant studies have found that KS is not efficient for identifying cancer patients suitable for VTE prevention ( Nichetti et al, 2019 ; Icht et al, 2021 ; Kewan et al, 2021 ; Moik et al, 2021 ). Only one study has shown that a KS ≥ 1 is significantly associated with VTE ( Sussman et al, 2021 ).…”