Bevacizumab in high-grade glioma patients following intraparenchymal hemorrhage

Background Intraparenchymal hemorrhage (IPH) is a relative contraindication to bevacizumab therapy, an antivascular endothelial growth factor (VEGF) monoclonal antibody approved for the treatment of recurrent glioblastoma. However, in patients with symptomatic enhancing tumors and poor functional status, bevacizumab may be the only beneficial therapeutic option. Methods We retrospectively reviewed all patients with high-grade glioma who were treated between January 1, 2005 and December 31, 2014 with bevacizumab despite prior IPH. Results Eighteen patients met our study criteria. There were 12 women and 6 men with a median age of 56 years. Tumor types were glioblastoma (n = 15), anaplastic astrocytoma (n = 2), and anaplastic oligodendroglioma (n = 1). Seventeen patients had prior spontaneous intratumoral bleed (13 grade 1-2; 4 grade 3-4); the 1 remaining patient had a grade 3 bleed due to cerebral venous thrombosis. Among them, identifiable risk factors for hemorrhage were anti-VEGF therapy, anticoagulation use, thrombocytopenia, and hypertension; seven had no identifiable risk factors. The median duration from IPH to (re-)initiation of bevacizumab was 113 days (range 13-1367). Brain imaging performed prior to bevacizumab treatment showed persistent or evolving hemorrhage in 8 patients and complete resolution in 10 patients. With a median follow-up duration of 137 days after bevacizumab re-initiation, only 1 (6%) of the 18 patients re-bled; this patient had an anaplastic oligodendroglioma and developed a grade 2 intratumoral bleed after 3 doses of bevacizumab. Conclusions The incidence of re-bleed is rare. Bevacizumab use was safe in patients with recurrent high-grade glioma following IPH for whom no other meaningful treatment options existed.