{Author 1 (Prefix):11.2} {Author 1 (Last):11.6}

TitelClinical Phenotype and Management of Severe Neurotoxicity Observed in Patients with Neuroblastoma Treated with Dinutuximab Beta in Clinical Trials
Einleitung

Neurotoxicity is an off-tumour, on-target side effect of GD2-directed immunotherapy with monoclonal antibodies.

Patient/en und Methoden

Here, we report the frequency, management and outcome of patients enrolled in two prospective clinical trials who experienced severe neurotoxicity during immunotherapy with the anti-GD2 antibody dinutuximab beta (DB) administered as short-term infusion (HR-NBL1/SIOPEN study, randomisation R2, EudraCT 2006-001489-17) or as long-term infusion (HR-NBL1/SIOPEN study, randomisation R4, EudraCT 2006-001489-17 and LTI/SIOPEN study, EudraCT 2009-018077-31), either alone or with subcutaneous interleukin-2 (scIL-2).

Ergebnisse

The total number of patients included in this analysis was 1102. Overall, 44/1102 patients (4.0%) experienced Grade 3/4 neurotoxicities (HR-NBL1 R2, 21/406; HR-NBL1 R4, 8/408; LTI study, 15/288), including 27 patients with severe neurotoxicities (2.5%). Events occur predominantly in patients receiving combined treatment with DB and scIL-2. Neurotoxicity was treated using dexamethasone, prednisolone, intravenous immunoglobulins and, in two patients, plasmapheresis, which was highly effective. While neurological recovery was observed in 16 of 21 patients with severe neurotoxicities, 5/1102 (0.45%) patients experienced persistent and severe neurological deficits.

Schlussfolgerung/Diskussion

In conclusion, severe neurotoxicity is most commonly observed in patients receiving DB with scIL-2. Considering the lack of clinical benefit for IL-2 in clinical trials so far, the administration of IL-2 alongside DB is not recommended.

Autor*in 1Ruth Ladenstein Department for Studies and Statistics and Integrated Research at the Children’s Cancer Research Institute and St. Anna Children’s Hospital, Department of Paediatrics, Medical University, 1090 Vienna
Autor*in 2Aleksandra Wieczorek Pediatric Hematology Oncology, Jagiellonian University Medical College, 30-663 Krakow, Poland
Autor*in 3Carla Manzitti Oncology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
Autor*in 4Alberto Garaventa Oncology Unit, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy
Autor*in 5Juliet Gray Centre for Cancer Immunology, University of Southampton, Southampton SO16 6YD, UK
Autor*in 6Vassilios Papadakis Department of Pediatric Hematology-Oncology, Agia Sofia Children’s Hospital, 11527 Athens, Greece
Autor*in 7Dominique Valteau-Couanet Children and Adolescent Oncology Department, Gustave Roussy, 94805 Villejuif, France
Autor*in 8Katarzyna Zachwieja Department of Pediatric Nephrology and Hypertension, Jagiellonian University Medical College, 30-663 Krakow, Poland
Autor*in 9Ulrike Poetschger Department for Studies and Statistics and Integrated Research, Children’s Cancer Research Institute, 1090 Vienna, Austria
Autor*in 10Ingrid Pribill Department for Studies and Statistics and Integrated Research, Children’s Cancer Research Institute, 1090 Vienna, Austria
Autor*in 11Stefan Fiedler Department for Studies and Statistics and Integrated Research at the Children’s Cancer Research Institute and St. Anna Children’s Hospital, Department of Paediatrics, Medical University, 1090 Vienna
Autor*in 12Holger Lode Pediatric Hematology and Oncology, University Medicine Greifswald, 17475 Greifswald, Germany