Children with medulloblastoma treated with modified ACNS0821 temozolomide, irinotecan, and bevacizumab: the Seattle Children’s Hospital experience

Abstract

Abstract Background Effective therapy for medulloblastoma at the time of relapse is limited. The objective of this study is to review outcomes from the Seattle Children’s Hospital (SCH) institutional standard therapy for relapsed medulloblastoma, modified from the published ACNS0821 regimen. Methods Retrospective review of patients treated for relapsed medulloblastoma from 2012-2024 treated with modified ACNS0821 therapy, including combination bevacizumab, irinotecan and temozolomide, referred to as “TIB”. Each TIB cycle includes oral temozolomide (200 mg/m2/day) for the first 5 days, intravenous (IV) bevacizumab (10 mg/kg/dose) and IV irinotecan (125 mg/m2/dose or 340 mg/m2) on days 1 and 15 of each cycle. Patient medical history, prior treatment, therapy toxicity, response and outcome were collected. Analysis included Kaplan-Meier estimates of 3-year overall survival (OS) and 3-year progression free survival (PFS). Results Fifteen patients were treated with TIB for relapsed medulloblastoma at SCH (median age 5.81 (0.21 – 23.6) years, 60% male). Twelve patients completed planned therapy. Therapy was discontinued for toxicity (n=1) and family preference (n=1). Most common toxicities were thrombocytopenia (n=7), neutropenia (n=4), nausea (n=5), vomiting (n=5), diarrhea (n=3). Five patients required dose modification of one agent for toxicity. Median follow up from TIB therapy start was 1.61 (0.47 – 7.66) years. 3-year OS was 48% (95% CI: 18-74%) and 3-year EFS was 16% (95% CI: 1-49%). Conclusions TIB was well-tolerated in pediatric patients with relapsed medulloblastoma, and outcomes were similar to those published in clinical trials. TIB therapy should be considered for patients with relapsed medulloblastoma, especially patients with limited access to care due to travel barriers.