A phase 2 randomized study of chemoimmunotherapy with or without eflornithine (DFMO) in relapsed/refractory neuroblastoma: A Children’s Oncology Group (COG) report.

• DOI: 10.1200/jco.2025.43.16_suppl.10001
• Publication Date: 2025-05-28T21:06:45Z
• Authors: Margaret E. Macy; Arlene Naranjo; Fan F. Zhang; Michael Acord; Thomas Cash; Steven G. DuBois; Jennie Haunani Fo...; Kristin R. Knight; Michael D. Hogarty; Rajen Mody; Daniel A. Morgens...; Marguerite T. Parisi; Navin Pinto; C. Patrick Reynolds; Michelle E Keyel; Barry L. Shulkin; David Simon Ziegler; Rochelle Bagatell; Julie R. Park; Kelly C. Goldsmith
• Keywords: Chemoimmunotherapy; Cog; Eflornithine; Refractory (planetary science); Lomustine

10001 Background: Dinutuximab, irinotecan, temozolomide and GM-CSF (DIT) is widely used in first relapsed/ refractory high-risk neuroblastoma (r/r HRNB), however <50% of patients (pts) respond. ODC1 a key enzyme important for NB cell survival. Difluoromethylornithine (DFMO) irreversibly inhibits ODC1, suppressing polyamine biosynthesis driving anti-NB activity. DFMO also arginase may enhance immunotherapy r/r NB. COG ANBL1821 was randomized phase 2 study pts with that evaluated response to DIT or without (NCT03794349). Methods: Patients episode were 1:1 (Arm A) (6750 mg/m divided TID; Arm B). They stratified by measurable/evaluable disease, MYCN status, prior anti-GD2 therapy, therapy. Cycles 21 days. On B, initially given continuously; discontinuous dosing (days 1-7 15-21) instituted due ototoxicity the initial cohort. Objective Response Rate [(ORR); sum complete (CR), partial (PR), minor (MR) responses per 2017 International Neuroblastoma Criteria (INRC)] determined based on central review imaging. Toxicities graded CTCAE v5.0. Results: 91 eligible evaluable (44 A, 47 B) May 2019-Jan 2024. 28/44 (63.6%) A 32/47 (68.1%) B had relapsed progressive disease (RPD); remaining disease. The ORR 61.4% (27/44) 57.4% (27/47) (p=0.566). 22/44 (50%) achieved CR PR compared 23/27 (48.9%) B. rates RPD similar those both arms. 1-year progression-free survival (PFS) 70.0±8.0% 56.8±8.2% Overall 87.0±5.7% 81.4±6.3% Arms respectively. most common toxicities reported arms hematologic gastrointestinal. Fewer (n=7) Grade 3+ pain than (n=15) (p=0.0326). Hearing loss toxicity interest; continuous dosing, 55.6% (5/9) developed hearing requiring dose hold. With 15.8% (6/38) 6.3% (2/32) (p=0.275). 14/16 (87.5%) NB+ marrows GD2+ at enrollment; GD2 not detected persisting cells therapy analyzed. Conclusions: addition did improve HRNB, though confirmed activity this population. higher previously reported, likely use INRC includes MR calculation ORR. Rates CR+PR trial reported. associated an increased incidence which partially mitigated dosing. Clinical information: NCT03794349 .