Thrombotic Complications Associated with Immune Checkpoint Inhibitors

Abstract

Thromboembolism is a common complication in patients with cancer and is associated with significant morbidity and mortality. Anticancer treatment is a known risk factor of cancer-associated thrombosis. Immune checkpoint inhibitors have become a mainstay of treatment in various cancers. Both venous and arterial thrombosis have been increasingly reported as adverse events associated with immune checkpoint inhibitors in recent studies, with a cumulative incidence of venous thrombosis to be 5–8% at 6 months and over 10% at 12 months. Additionally, rates of approximately 1–5% for arterial thrombosis were reported at 12 months. Data also showed an association of thromboembolism with adverse survival. Many pertinent clinical questions in this population deserve further investigation, including the risks of thrombosis associated with immune checkpoint inhibitors as compared to those with traditional systemic therapy, associated risk factors, and the optimal prevention and treatment strategies. In this review, we synthesize data from available literature, provide relevant information for clinicians and potential future directions for research.

Immune checkpoint inhibitors-associated thrombosis in patients with lung cancer and melanoma: a study of the Spanish society of medical oncology (SEOM) thrombosis and cancer group

“…For example, Wang et al [ 11 ] performed a bibliographic review of VTE/AT associated with ICI. The patient profile most often associated with this type of complication was male, with stage IV disease, and with a primary lung, kidney, or melanoma.…”

Understanding immune perspectives and options for the use of checkpoint immunotherapy in HCC post liver transplant

“…Registry trials that led to the ultimate approval of ICI use for the treatment of HCC did not include liver (and other solid organ) transplant recipients as study participants. Hence, most of the data on the efficacy and safety of ICIs in these patients are drawn from case reports, case series and single center experiences [56][57][58][59][60] . A summary of some studies evaluating the efficacy and adverse events of these medications in the transplant population is summarized in Table 2.…”

“…Initial reports documented rates of rejection in transplant recipients treated with ICIs, anywhere from 36% in LT to 54% in kidney transplant recipients [67] . Systematic reviews have evaluated the risk of rejection in SOT recipients treated with ICIs [60,68] . These reviews are quite heterogenous: including a mix of SOT recipients with a variety of solid tumor malignancies.…”

“…These reviews are quite heterogenous: including a mix of SOT recipients with a variety of solid tumor malignancies. One singlecenter analysis of 17 SOT (including 8 LT) recipients treated with ICIs found that 18% of patients had acute allograft rejection, a cumulative incidence of cancer progression of 50% at 6 months, and 65% mortality over the median follow up period of 4.6 months [60] . Another pooled analysis of 64 SOT recipients documented the rate of allograft rejection at 41% following checkpoint immunotherapy for malignancies in the posttransplant period.…”

“…Relative safety, especially with close monitoring, has been described in a few case reports, but severe and sometimes fatal outcomes have also been published [ 56 , 57 , 59 ] . Some of the main adverse effects to be considered, especially in an LT recipient, are that of venous (sub-distribution HR up to 1.36 depending on the agent) and arterial thrombosis [ 61 , 62 ] . Poor wound healing is also a concern given the overlapping cellular and molecular processes between wound healing and cancer; but this increased risk has not been apparent in studies, and ICIs have been suggested to be safe in the peri-operative period [ 63 – 65 ] .…”