BIOM-12. PROLONGED RESPONSE TO THIRD-LINE TREATMENT WITH COMBINATION CCNU/TMZ IN AN MGMT METHYLATED IDH-WILDTYPE GLIOBLASTOMA

Abstract INTRODUCTION Multiply recurrent glioblastoma suffers from poor response rates to treatment, and limited durability. We describe a case of an impressive third-line CCNU/TMZ. BACKGROUND Headaches brought 76-year-old man medical attention. MRI identified enhancing right temporal mass -- path following resection demonstrated (IDH-wildtype, MGMT-methylated, TERT mutant; PTEN Y68H, CDKN2A/B loss, CCND3 amplification; VUS in POLE, ATM, GRIN2A, ROS1). He received hypofractionated RT 40.05Gy/15-fractions plus 21-days concurrent TMZ 75 mg/m2, then 5-day-on / 23-day-off (150 mg/m2 cycles #1-3; 200 subsequent). pre-cycle #6, nearly 6 months post-RT, showed increased enhancement/FLAIR consistent with local progression (POD).Second-Line: After screen-fail for clinical trial, initiated off-label regorafenib 160 mg/d, 21-days-on/7-days-off partial enhancement at 3 weeks. With dose-reduction 120 mg/d #2-3 (for mounting fatigue), progressively worsened. Despite resuming higher cycle #4, progressed, POD.Third-Line: Given presence MGMT promoter methylation (and extrapolating CeTeG/NOA-09), combination CCNU 100 (day 1) (days 2-6; 8-week cycle) was started. There improvement enhancement/FLAIR, which continued improve gradually through Durability surprising MRIs stable/improved 15 since starting DISCUSSION This illustrates CCNU/TMZ the third-line. Delayed treatment effect is less likely given time elapsed initial (after 5 adjuvant TMZ), convincing but short-lived (that worsened more cycles), robust only also never on steroids (except post-operatively) nor bevacizumab. suggests that mediated by antitumor against progressing tumor, rather than delayed effect. may have played role this patient's dual alkylator therapy.