Chemo-immunotherapy with dinutuximab beta in patients with relapsed/progressive high-risk neuroblastoma: does chemotherapy backbone matter?

Patricia Raiser, Gudrun Schleiermacher, Marion Gambart, Benoit Dumont, Anne Sophie Defachelles, Estelle Thebaud, Julie Tandonnet, Claudia Pasqualini, Stéphanie Proust, Natacha Entz-Werle, Isabelle Aerts, Lee A. Ndounga-Diakou, Arnaud Petit, Chloe Puiseux, Camille Khanfar, Jeremie Rouger, Ludovic Mansuy, Joy Benadiba, Frédéric Millot, Claire PluchartSalim Laghouati, Birgit Geoerger, Gilles Vassal, Dominique Valteau-Couanet, Pablo Berlanga

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    2 Citations (Scopus)

    Abstract

    Background: Addition of anti-GD2 antibodies to temozolomide-based chemotherapy has demonstrated increased antitumor activity and progression-free survival in patients with relapsed/progressive high-risk neuroblastoma. However, chemo-immunotherapy is not yet approved for this indication. This study presents the chemo-immunotherapy experience in patients with relapsed/progressive high-risk neuroblastoma treated within the off-label use program of the Neuroblastoma Committee of the French Society of Pediatric Oncology (SFCE). Methods: Dinutuximab beta (dB) was administered alongside temozolomide-topotecan (TOTEM) or temozolomide-irinotecan (TEMIRI) at first disease relapse/progression or topotecan-cyclophosphamide (TopoCyclo) at further relapse/progression. Real-world data on demographics, treatment, antitumor activity and safety was collected from all patients after inclusion in SACHA-France (NCT04477681), a prospective national registry, which documents safety and efficacy data on innovative anticancer therapies prescribed to patients ≤ 25 years old as compassionate or off-label use. Results: Between February 2021 and July 2023, 39 patients with confirmed relapsed/progressive high-risk neuroblastoma (median age 6 years, range 1–24) were treated with dB+TopoCyclo (n = 24) or dB+TOTEM/TEMIRI (n = 15) across 17 centers. In total, 163 chemo-immunotherapy cycles were administered, main toxicities were mild or moderate, with higher incidence of hematological adverse drug reactions with dB+TopoCyclo than dB+TOTEM/TEMIRI. Objective response rate was 42% for dB+TopoCyclo (CI95% 22–63%) and 40% for dB+TOTEM/TEMIRI (CI95% 16–68%). Conclusion: Similar objective response rates for dB+TopoCyclo and dB+TOTEM/TEMIRI in patients with relapsed/progressive high-risk neuroblastoma emphasize the importance of chemo-immunotherapy, irrespective of the chemotherapy backbone.

    Original languageEnglish
    Article number114001
    JournalEuropean Journal of Cancer
    Volume202
    DOIs
    Publication statusPublished - 1 May 2024

    Keywords

    • Chemotherapy
    • Dinutuximab beta
    • Immunotherapy
    • Neuroblastoma
    • Real-world data
    • Relapse

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