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.