Immunotherapy by anti-GD2 antibodies in patients with primary high-risk neuroblastoma, primary resistant and relapsed disease: Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, First Pavlov State Medical University of St. Petersburg experience
Authors: Kazantsev I. V. , Gevorgyan A. G. , Yukhta T. V. , Drozdovskaya D. A. , Tolkunova P. S. , Goncharova E. V. , Kozlov A. V. , Golenkova M. S. , Galimov A. N. , Bogdanova O. I. , Punanov Yu. A. , Kulagin A. D. , Zubarovskaya L. S. 
Published: October 2021

Introduction. The long-term event-free survival of patients with high-risk neuroblastoma (NB) receiving intensive complex therapy according to current russian standard do not exceed 40 %. Also, there is no standard tactics in patients with primary resistant and relapsed disease, most of them die due to disease progression. While, anti-GD2 immunotherapy (IT) proved to be effective in patients with high-risk NB, in Russian Federation this method is not generally available. There are currently two pilot studies ongoing in Raisa Gorbacheva Memorial Institute aimed to evaluate the effectiveness of anti-GD2 antibodies in high-risk NB patients.Aim of the study – describing a single-center experience of anti-GD2 IT in primary high-risk NB patients and patients with primary resistant and relapsed disease.Materials and methods. A total of 20 patients received anti-GD2 antibodies, 16 of them were included into pilot trials. The median age at IT initiation was 5 (3–17) years. In 13 cases the therapy was initiated in patients with high-risk disease after auto-HSCT, in 3 cases – in patients with 1st systemic relapse of primary resistant disease after 2nd-line therapy and haplo-HSCT, in 1 case – in patient with 2nd chemosensitive relapse after haplo-HSCT. Also, 3 patients with progressive chemoresistant disease received anti-GD2 antibodies as monotherapy (n = 1) or in combination with chemotherapy (n = 2) as salvage regimen.Results. Patients receiving anti-GD2 antibodies after auto-HSCT retain response to therapy in 11 of 13 cases with a median follow-up period of 15 (6–27) months, in 2 cases there was disease progression during or immediately after IT cessation. Both patients with disease progression responded well to salvage therapy. Two of 3 haplo-HSCT recipients with prior good response to 2nd-line therapy are currently in remission 16 and 36 months past haplo-HSCT, one patient progressed 55 months after transplantation. A patient with 2nd late relapse after haplo-HSCT currently maintains remission on IT. Both patients with chemorefractory progressive disease did not respond to IT and died due to disease progression. IT was characterized by acceptable toxicity. In most cases it was complicated by Gr 1–2 fever, rash or neuropathic pain effectively controlled by supportive therapy. However, three patients had signs of neurotoxicity requiring therapy termination in one case.Conclusion. Dinutuximab beta IT is characterized by acceptable toxicity. With a median follow-up of 18 (6–59) months the majority (14 of 17) patients receiving anti-GD2 antibodies as maintenance therapy after auto- or allogeneic HSCT retain response. However, we did not observe any response in patients with progressive chemorefractory disease.