Chemo-immunotherapy with dinutuximab beta in patients with relapsed/progressive high-risk neuroblastoma: does chemotherapy backbone matter?
Patricia Raiser, Gudrun Schleiermacher, Marion Gambart, Benoît Dumont, Anne Sophie Defachelles, Estelle Thébaud, Julie Tandonnet, Claudia Pasqualini, Stéphanie Proust, Natacha Entz‐Werlé, Isabelle Aerts, Lee Aymar Ndounga‐Diakou, Arnaud Petit, Chloé Puiseux, Camille Khanfar, Jérémie Rouger, L Mansuy, Joy Benadiba, Frédéric Millot, Claire Pluchart, Salim Laghouati, Birgit Geoerger, Gilles Vassal, Dominique Valteau‐Couanet, Pablo Berlanga
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.