Multicenter phase II study of temozolomide and myeloablative chemotherapy with autologous stem cell transplant for newly diagnosed anaplastic oligodendroglioma

作者：Thomas Alissa A; Abrey Lauren E; Terziev Robert; Raizer Jeffrey; Martinez Nina L; Forsyth Peter; Paleologos Nina; Matasar Matthew; Sauter Craig S; Moskowitz Craig; Nimer Stephen D; DeAngelis Lisa M; Kaley Thomas; Grimm Sean; Louis David N; Cairncross J Gregory; Panageas Katherine S; Briggs Samuel; Faivre Geraldine; Mohile Nimish A; Mehta Jayesh; Jonsson Philip; Chakravarty Debyani; Gao Jianjiong; Schultz Nikolaus; Brennan Cameron W; Huse Jason T

来源：Neuro-Oncology, 2017, 19(10): 1380-1390.

DOI：10.1093/neuonc/nox086

• 1p/19q codeletion
• anaplastic oligodendroglioma
• autologous stem cell transplant
• temozolomide

Background. Anaplastic oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA) are chemotherapy-sensitive tumors with prolonged survival after radiochemotherapy. We report a prospective trial using induction temozolomide (TMZ) followed by myeloablative high-dose chemotherapy (HDC) with autologous stem-cell transplant (ASCT) as a potential strategy to defer radiotherapy.
Methods. Patients with AO/AOA received 6 cycles of TMZ (200 mg/m(2) x 5/28 day). Responding patients were eligible for HDC (thiotepa 250 mg/m(2)/day x 3 days, then busulfan 3.2 mg/kg/day x 3 days), followed by ASCT. Genomic characterization was performed using next-generation sequencing.
Results. Forty-one patients were enrolled; 85% had 1p/19q codeleted tumors. After induction, 26 patients were eligible for HDC-ASCT and 21 agreed to proceed. There were no unexpected adverse events or toxic deaths. After median follow-up of 66 months, 2-year progression-free survival (PFS) for transplanted patients was 86%, 5-year PFS 60%, and no patient has died. Among all 1p/19q codeleted patients (N = 33), 5-year PFS was 50% and 5-year overall survival (OS) 93%, with median time to radiotherapy not reached. Next-generation sequencing disclosed typical oligodendroglioma-related mutations, including IDH1, TERT, CIC, and FUBP1 mutations in 1p/19q codeleted patients, and glioblastoma-like signatures in 1p/19q intact patients. Aside from IDH1, potentially oncogenic/actionable mutations were variable, depicting wide molecular heterogeneity within oligodendroglial tumors.
Conclusions. TMZ followed by HDC-ASCT can be safely administered to patients with newly diagnosed 1p/19q codeleted AO. This strategy was associated with promising PFS and OS, suggesting that a chemotherapy-based approach may delay the need for radiotherapy and radiation-related toxicities. Raw data for further genomic and meta-analyses are publicly available at http://cbioportal.org/study?id=odg_msk_2017, accessed 6 January 2017.

• 出版日期2017-10