Venous thromboembolism in patients with B-cell non-Hodgkin lymphoma treated with lenalidomide: a systematic review and meta-analysis.

Lenalidomide is associated with increased risk of thromboembolism (VTE) in patients with multiple myeloma. This risk has not previously been defined in B-cell non-Hodgkin lymphoma (NHL), for which lenalidomide is also an active agent. We conducted a systematic literature search in Ovid MEDLINE (1946 to February 2017), Ovid EMBASE (1974 to February 2017), The Cochrane Library (Wiley), and Web of Science Core Collection for prospective studies evaluating lenalidomide-containing regimens in B-cell NHL with adequate reporting of patient characteristics, total cycles received, and safety data including VTE rates. The primary outcome was VTE events per 100 patient-cycles by meta-analysis using random-effects models. Our literature search identified 1719 citations; 28 articles were included. For all patients with B-cell NHL receiving lenalidomide, the rate of VTE per 100 patient-cycles was 0.77 (95% confidence interval [CI], 0.48-1.12; I2, 67%). The rate for single-agent lenalidomide was 1.09 events per 100 patient-cycles (95% CI, 0.49-1.94; I2, 76%), the rate for lenalidomide plus biologics was 0.49 (95% CI, 0.17-0.97; I2, 59%), and the rate for lenalidomide plus chemotherapy was 0.89 (95% CI, 0.39-1.60; I2, 57%). Rate of VTE events in B-cell NHL patients treated with lenalidomide in clinical trials is similar to the rate in multiple myeloma. The VTE rate appears to be lowest for lenalidomide combined with a biologic compared with single-agent lenalidomide or its combination with chemotherapy. This protocol was registered at www.crd.york.ac.uk/prospero/ as #CRD42017056042.