Bevacizumab for radiation necrosis of the brain or steroid-refractory edema in patients with melanoma receiving immune checkpoint inhibitors.
Authors: Lopetegui-Lia Nerea , Dima Danai , Osantowski Bennett , Davis Robin , Song Jung Min , McNamara Michael J. , Suh John H. , Chao Samuel T. , Funchain Pauline , Kennedy Lucy Boyce 
Published: June 2022

e14008

Background: For patients with melanoma brain metastasis (MBM) treated with stereotactic radiosurgery (SRS), 5-6.5% develop radiation necrosis of the brain (RNB), which is commonly treated with corticosteroids (CS). Nonetheless, high-dose CS may reduce efficacy of immunotherapy (IO). Bevacizumab (BV) has been shown to reduce symptoms and peritumoral edema associated with RNB. However, data on the efficacy and toxicity of BV in patients with MBM who also receive IO is limited. We aimed to describe clinical features and outcomes of patients with MBM who received BV and were also treated with IO. Methods: Under an IRB-approved protocol, patients with MBM who developed RNB or steroid-refractory edema (SRE) and were treated with BV were identified. The selection criteria were as follows: (1) one or more MBM; (2) prior SRS for MBM; (3) development of RNB or SRE detected radiographically or based on expert opinion; (4) treatment with one or more cycles of BV; (5) treatment with IO for metastatic melanoma. Results: In this single-center retrospective series, 8 patients received IO and BV: 4 concurrently and 4 patients received IO immediately prior to or after BV. IO therapy included ipilimumab-nivolumab, nivolumab alone or pembrolizumab. Median number of MBM was 3.6 (range, 1-8) and median number of RNB/SRE foci were 1.125 (range, 1-2). Median time from diagnosis of RNB/SRE to initiation of BV was 1.4 months (range, 0.5-3 months). BV dosing regimen was 5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks or 10 mg/kg every 2 weeks. 71% (5 of 7) patients who required CS for RNB/peritumoral edema symptoms at the time of starting BV were able to taper CS after receiving BV or stop CS completely. This allowed for 4 of these patients to subsequently start or resume IO. 28% (2 of 7) patients had increasing neurological symptoms during CS taper and required an increase in CS dosing. Only 1 patient was not on CS at the time of BV initiation. 75% (6 of 8) cases attained intracranial radiologic response, with documented decreased edema or tumor size, or resolution of enhancement on MRI; 1 patient had stable disease after BV; and 1 patient had continued clinical deterioration despite BV. 62.5% (5 of 8) patients had no adverse events from BV, but 37.5% (3 of 8) had DVT/PE, 1 requiring a thrombectomy, and 1 additionally had perforated diverticulitis. Median follow-up time from BV administration was 17.94 months (range, 1-58 months), with 75% (6 of 8) patients with survival > 10 months. Conclusions: Treatment of RNB/SRE with BV in patients with MBM receiving IO appears to be effective and relatively well tolerated, though with occasional serious adverse events. BV led to improvement of symptoms and allowed for CS taper in a substantial proportion of patients. By reducing CS requirement, BV may permit continuation of IO, which leads to durable survival in a large proportion of patients.