Anaemia, Thrombocytopenia With ICI Use Predict Poor Outcome For Stage IV Cancer Patients

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: A review of stage IV cancer patients using immune checkpoint inhibitors (ICIs) has detected a possible risk of clinically significant bleeding and a potential correlation with poor overall survival (OS) among those who develop anaemia or thrombocytopenia. 

The investigators collated information for 529 stage IV cancer patients treated at the Cleveland Clinic Foundation in Ohio, USA, between January 2015 and July 2019, most commonly with lung or genitourinary cancer or melanoma. The patients were receiving nivolumab, pembrolizumab, ipilimumab, atezolizumab, avelumab or durvalumab, with 15.1% given two or more ICIs. 

Overall, 101 clinically significant bleeding events, defined as admission to hospital for bleeding, requirement for 2 or more units of blood, a 2 g/dL or greater decrease in haemoglobin, or death, were identified in 16.8% of the cohort during ICI use, the researchers explain in a letter to the European Journal of Cancer. 

Specifically, bleeding occurred a median of 4 months after initiation of ICI use; this affected the gastrointestinal tract in 27.7% of patients, while 23.8% had intracerebral events, 12.9% haemoptysis and 8.9% intramuscular haematomas, report Tariq Kewan, from Cleveland Clinic Fairview Hospital in Ohio, USA, and co-authors. 

When patients in the cohort with clinically significant bleeding were compared with those without, bleeding events were significantly associated with African American ethnicity (12.4 vs 4.8%) and baseline anaemia (83.1 vs 56.1%) but did not appear to be linked to the type of cancer or specific ICI used. 

Median duration of OS did not significantly differ between patients who did and did not experience clinically significant bleeding within 3 months of ICI initiation, at 12.8 versus 13.1 months.  

However, median OS was significantly shorter among patients who were diagnosed with anaemia (11.1 vs 20.8 months) or thrombocytopenia (11.0 vs 20.6 months) within 3 months of ICI use, although there was no correlation between initiation of any specific ICI and an increased risk of developing anaemia or thrombocytopenia in this time frame. 

The investigators acknowledge that the study is limited by its retrospective nature, the lack of a control group and the presence of other contributing factors to anaemia and thrombocytopenia in the patient cohort. 

But they counter that their study collated data on “a large number of patients with stage IV cancer treated with ICIs” and “concentrated on the clinical outcomes and bleeding because an absolute platelet count is not important without clinical effect or bleeding.” 

Tariq Kewan et al conclude: “[O]ur study suggests that new anaemia and thrombocytopenia in patients with stage IV cancer treated with ICIs are associated with poor survival outcomes” and recommend that “[c]linicians should be vigilant against clinically significant bleeding early after starting [ICI] treatment.” 

They add: “Future studies are needed to compare the incidence of bleeding in patients with different antineoplastic therapies.” 

Reference  

Kewan T, Covut F, Ahmed R, et al. Clinically significant bleeding with immune checkpoint inhibitors: A retrospective cohort study. Eur J Cancer; Advance online publication 15 August 2020. doi:10.1016/j.ejca.2020.07.005