Efficacy and Tolerability of Topotecan/Cyclophosphamide/Dinutuximab in Relapsed and Refractory High-Risk...

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.

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.

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.

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.