Dinutuximab beta in the treatment of high-risk neuroblastoma

Abstract

Despite therapeutic advances, high-risk neuroblastoma is still associated with a poor long-term prognosis. Immunotherapy with the anti-GD2 antibody dinutuximab beta has recently been added to the standard of care for patients with high-risk neuroblastoma in our center in Bratislava, and our initial experience with dinutuximab beta has been reported previously. Here we provide a follow-up on the outcomes of 7 patients who were treated with dinutuximab beta under clinical practice conditions at our center. Medical records of 31 patients diagnosed with neuroblastoma between 2017 and 2020 at the Children's Hematology and Oncology Clinic in Bratislava were retrospectively reviewed and 7 patients with high-risk neuroblastoma who were treated with dinutuximab beta were identified. All 7 patients received dinutuximab beta as continuous infusion over 10 days at a dose of 10 mg/m 2 /day for 5 cycles, following induction and consolidation therapy. Supportive therapy was administered to manage adverse events. Clinical outcomes and treatment tolerance were evaluated. Six of 7 patients treated with dinutuximab beta achieved complete remission, with a median duration of response of 21.5 months as of January 2022, and 1 displayed stable disease 21 months after treatment completion. Treatment was tolerable in most patients, with the majority of adverse events managed with supportive care. Dinutuximab beta is an effective immunotherapy for patients with high-risk neuroblastoma in routine clinical practice when coupled with optimal supportive management of adverse events.

Dinutuximab Beta in Children with High-Risk Neuroblastoma: Experience from a Single Center in Croatia

“…Only two patients reported moderate pain in the current case series, one of whom also received IL-2, which has been shown to be associated with a higher incidence of pain when combined with dinutuximab beta [ 8 , 21 ]. The feasibility, tolerability and effectiveness of dinutuximab beta administration in real-world clinical practice was also demonstrated in a recent single-center experience in Slovakia [ 22 , 23 ]. In this small case series, dinutuximab beta resulted in complete remission in six of seven patients with HRNB, and was tolerable in most patients, with the majority of AEs managed with supportive therapy [ 23 ].…”

“…The feasibility, tolerability and effectiveness of dinutuximab beta administration in real-world clinical practice was also demonstrated in a recent single-center experience in Slovakia [ 22 , 23 ]. In this small case series, dinutuximab beta resulted in complete remission in six of seven patients with HRNB, and was tolerable in most patients, with the majority of AEs managed with supportive therapy [ 23 ].…”

Neuroblastoma and its Target Therapies: A Medicinal Chemistry Review

“…Tumour antigens targeted for immunotherapy in patients with NB thus far are chiefly expressed on the cell surface, the gangliosides GD2 being the most common with GD2 mAbs Dinutuximab being an example of this. [65] Gangliosides are glycosylated lipid molecules containing sialic acid residues in their carbohydrate structure. [66] In normal cells, GD2 (Figure 28) is not expressed or only to a low extent, and is largely limited to neuron, skin melanocytes, and peripheral pain fibers.…”

“…mAbs can target intracellular antigens if they internalize after binding. Tumour antigens targeted for immunotherapy in patients with NB thus far are chiefly expressed on the cell surface, the gangliosides GD2 being the most common with GD2 mAbs Dinutuximab being an example of this [65] …”

Dinutuximab Beta Maintenance Therapy in Patients with High-Risk Neuroblastoma in First-Line and Refractory/Relapsed Settings—Real-World Data

“…Currently, there are limited published data regarding the use of dinutuximab beta in real-world clinical practice [ 13 , 14 , 15 ]. Real-world data complement those from clinical trials providing further evidence of therapeutic effectiveness and safety in routine clinical practice.…”