Efficacy and Tolerability of Topotecan/Cyclophosphamide/Dinutuximab in Relapsed and Refractory High‐Risk Neuroblastoma: A Multi‐Institutional Retrospective Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: PURPOSE: Chemoimmunotherapy with irinotecan, temozolomide, and dinutuximab (I/T/DIN) has emerged as first-line therapy for relapsed/refractory (r/r) high-risk neuroblastoma (HRNB) in North America. Topotecan and cyclophosphamide (T/C) are often used in combination with dinutuximab in the setting of lack of response, progression, or incomplete response following I/T/DIN, but efficacy and tolerability are unknown. METHODS: Eligible patients received one or more cycles of T/C/DIN for r/r HRNB. Response was assessed using the 2017 International Neuroblastoma Response Criteria. RESULTS: Fifty-four patients with r/r HRNB were included. Patients received a median of four cycles of T/C/DIN (range = 1-16); 48 (89%) had previously received I/T/DIN. Twenty-three patients (42.6%) had an objective response (complete/partial/minor; OR) to T/C/DIN, 21 (38.9%) had stable disease, and 10 (18.5%) had progressive disease as best response. Among patients who previously received I/T/DIN, objective response rate (ORR) to T/C/DIN was 54% in those with prior OR to I/T/DIN and 23% in those without prior OR (adjusted odds ratio 4.40, 95% confidence interval [CI]: 1.09-17.75). Patients who had experienced on-therapy progression with I/T/DIN had a similar ORR to T/C/DIN compared to those who never progressed (38% vs. 41%, p = 1.0). Twenty-one patients (39%) required T/C/DIN dose modification-11 (52%) due to hematologic toxicity. Seven patients (13%) discontinued T/C/DIN due to toxicity. CONCLUSION: T/C/DIN is an effective regimen for patients with r/r HRNB, producing ORRs similar to prior reports in chemoimmunotherapy-naïve patients treated with I/T/DIN. Prior chemoimmunotherapy response may predict response to T/C/DIN, but even patients who progress while receiving I/T/DIN may benefit from the T/C/DIN combination.
Source: Pediatric Blood & Cancer
Authors: Benjamin J. Lerman, Madeleine King, Rajen Mody, Sara‐Jane Onyeama, Araz Marachelian, Thomas Cash, Sara M. Federico, Meaghan Granger, Ami V. Desai, Suzanne Shusterman, Jennifer H. Foster, Elizabeth Sokol, Chelsee Greer, Keri Streby, Holly J. Meany, Kieuhoa T. Vo, Margaret E. Macy, Rochelle Bagatell
Institutions: University of California, San Francisco, University of California San Francisco Medical Center, C. S. Mott Children's Hospital, University of Southern California, Children's Hospital of Los Angeles, Emory University, Children's Healthcare of Atlanta, St. Jude Children's Research Hospital, University of Chicago, Harvard University, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Texas Children's Hospital, Lurie Children's Hospital, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Cook Children's Medical Center, Nationwide Children's Hospital, The Ohio State University, Children's National, Children's Hospital Colorado, University of Colorado Anschutz, Children's Hospital of Philadelphia, University of Pennsylvania
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
Funder: National Institutes of Health
OpenAlex ID: W7135238030