Xavier Deschênes-Simard1, Corentin Richard2, Loïck Galland3, Florence Blais4, Antoine Desilets1, Julie Malo2, Lena Cvetkovic1, Wiam Belkaid2, Arielle Elkrief1, Andréanne Gagné4, Marc-André Hamel4, Michèle Orain4, Philippe Joubert4, François Ghiringhelli3, Bertrand Routy1, Normand Blais5. 1. University of Montreal Research Center (CRCHUM), 900 Saint-Denis Street, Montreal, Quebec H2X 0A9, Canada; Hematology-Oncology Division, University of Montreal Health Centre (CHUM), 1000 Saint-Denis Street, Montreal, Quebec H2X 0A9, Canada. 2. University of Montreal Research Center (CRCHUM), 900 Saint-Denis Street, Montreal, Quebec H2X 0A9, Canada. 3. Dijon Bourgogne University Hospital, 2 Boul. du Maréchal de Lattre de Tassigny, 21000 Dijon, France. 4. Quebec Heart and Lung Institute Research Centre (CRIUCPQ), 2725 Sainte-Foy Road, Quebec City, Quebec G1V 4G5, Canada. 5. University of Montreal Research Center (CRCHUM), 900 Saint-Denis Street, Montreal, Quebec H2X 0A9, Canada; Hematology-Oncology Division, University of Montreal Health Centre (CHUM), 1000 Saint-Denis Street, Montreal, Quebec H2X 0A9, Canada. Electronic address: normand.blais.med@ssss.gouv.qc.ca.
Abstract
OBJECTIVES: Venous thrombotic events (VTEs) are a frequent complication of non-small cell lung cancer (NSCLC) and are associated with increased morbidity. Immune checkpoint inhibitors (ICIs) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of VTEs in NSCLC patients receiving these treatments. METHODS: A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of VTEs after ICIs was estimated using competing risk analysis, and the association of these events with survival and response to treatment was determined. Finally, univariate and multivariate tests were performed to identify VTE risk factors. RESULTS: The cumulative incidence of VTEs in the cohort was 14.8% (95% CI = 7.4-22.2%) for an incidence rate of 76.5 (95% CI = 59.9-97.8) thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. VTEs were not correlated with overall survival, progression-free survival, or objective response to ICIs. Age ˂ 65 years old (HR = 2.00; 95% CI = 1.11-3.59) and tumors with PD-L1 1-49% (HR = 3.36; 95% CI = 1.19-9.50) or PD-L1 ≥ 50% (HR = 3.22; 95% CI = 1.21-8.57) were associated with more VTEs after 12 months of ICI initiation. Also, a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 2.06; 95% CI = 1.09-3.89) and active smoking (HR = 2.00; 95% CI = 1.12-3.58) are probable risk factors of VTEs. CONCLUSION: This study suggests that the incidence of VTEs in NSCLC patients treated with ICIs is comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, VTEs were not associated with a decreased survival or response to therapy. Patient age < 65 and tumors with PD-L1 ≥ 1% were associated with a higher risk of VTEs under ICIs.
OBJECTIVES:Venous thrombotic events (VTEs) are a frequent complication of non-small cell lung cancer (NSCLC) and are associated with increased morbidity. Immune checkpoint inhibitors (ICIs) are revolutionizing the management of NSCLC, but little is known about their impact on thrombosis. This study aims to define the incidence and clinical relevance of VTEs in NSCLCpatients receiving these treatments. METHODS: A retrospective multicentric cohort study including 593 patients from three centers in Canada and France was performed. The cumulative incidence of VTEs after ICIs was estimated using competing risk analysis, and the association of these events with survival and response to treatment was determined. Finally, univariate and multivariate tests were performed to identify VTE risk factors. RESULTS: The cumulative incidence of VTEs in the cohort was 14.8% (95% CI = 7.4-22.2%) for an incidence rate of 76.5 (95% CI = 59.9-97.8) thrombosis per 1000 person-years, with most thromboses occurring rapidly after treatment initiation. VTEs were not correlated with overall survival, progression-free survival, or objective response to ICIs. Age ˂ 65 years old (HR = 2.00; 95% CI = 1.11-3.59) and tumors with PD-L1 1-49% (HR = 3.36; 95% CI = 1.19-9.50) or PD-L1 ≥ 50% (HR = 3.22; 95% CI = 1.21-8.57) were associated with more VTEs after 12 months of ICI initiation. Also, a delay of less than 12 months from diagnosis to the first ICI treatment (HR = 2.06; 95% CI = 1.09-3.89) and active smoking (HR = 2.00; 95% CI = 1.12-3.58) are probable risk factors of VTEs. CONCLUSION: This study suggests that the incidence of VTEs in NSCLCpatients treated with ICIs is comparable to what is reported in other cohorts of patients treated with chemotherapy. In our cohort, VTEs were not associated with a decreased survival or response to therapy. Patient age < 65 and tumors with PD-L1 ≥ 1% were associated with a higher risk of VTEs under ICIs.
Authors: Alok A Khorana; Nigel Mackman; Anna Falanga; Ingrid Pabinger; Simon Noble; Walter Ageno; Florian Moik; Agnes Y Y Lee Journal: Nat Rev Dis Primers Date: 2022-02-17 Impact factor: 65.038