Chemo‐Immunotherapy Rescue for High‐Risk Neuroblastoma Patients With Progressive Disease Before High‐Dose Chemotherapy: Real‐World Data From the SACHA‐France Study

Background Patients with high‐risk neuroblastoma (HR‐NBL) who experience disease progression (PD) during first‐line treatment prior to high‐dose chemotherapy (HDC) represent a rare and understudied subgroup, for whom treatment strategies are poorly defined and prognosis appears to be extremely poor. Aims We report real‐world data on the off‐label use of chemo‐immunotherapy for HR‐NBL patients with PD before HDC. The primary endpoint of our analysis is the best response during the chemo‐immunotherapy treatment. Methods The SACHA‐France registry prospectively documents safety and efficacy data on compassionate/off‐label treatments for patients of ≤25 years old (NCT04477681). Results Between January 2020 and September 2024, 13 patients with HR‐NBL received chemo‐immunotherapy due to PD before HDC, and were included in SACHA‐France. They had a median age of 3.4 years (1.3–8.0). Six patients had NMYC‐amplified disease. Five PD occurred during/end‐of‐induction chemotherapy, and eight during temozolomide‐based chemotherapy after initial insufficient metastatic response or toxicity. All but one had metastatic progression. The chemo‐immunotherapy consisted of topotecan–cyclophosphamide ( n = 9) or temozolomide–irinotecan ( n = 4), combined with dinutuximab beta (dB) for a maximum of six cycles. Objective responses (ORs) were seen in five of 13 patients (38%)—four partial responses (PR) and one complete response (CR). Three out of the five patients with PD during/end of induction had PR, including two with NMYC‐amplified tumors. Overall, six patients underwent tandem HDC, with two remaining progression‐free after 1.7 and 2.1 years, and one remaining disease‐free at 3.4 years. Conclusion Chemo‐immunotherapy can benefit HR‐NBL patients with PD before HDC, including those with progression during/at the end of the induction chemotherapy and NMYC amplification. These findings support its early inclusion in HR‐NBL trials.