Naxitamab with novel scheduling and stepped‐up dosing of GM ‐ CSF plus vaccine, but no myeloablative therapy for patients with high‐risk neuroblastoma in first complete remission

Abstract Naxitamab + GM‐CSF was effective against chemo‐resistant high‐risk neuroblastoma (HR‐NB), leading to approval by the Food and Drug Administration. We now describe toxicity and outcome of patients treated in first complete remission (CR) with naxitamab plus novel dosing of GM‐CSF (nGM‐CSF), initiated in February 2021, based on pharmacologic data. Treatment also included an anti‐NB vaccine but no prior myeloablative therapy (MAT). This retrospective study covers all first CR HR‐NB patients who started the novel naxitamab + nGM‐CSF regimen from February 22, 2021 to December 11, 2023. As before, naxitamab (3 mg/kg) was infused on days 1–3–5 (i.e., 3 doses/cycle). Previously, priming doses of GM‐CSF 250 μg/m 2 /day were subcutaneously administered ×5 (days −4 to 0), followed by step‐up to 500 μg/m 2 /day ×5 (days 1 to 5), but now priming doses were ×3 (days −2 to 0) and stepped‐up dosing was ×7 (days 1 to 7), that is, through 2 days after the last dose of naxitamab. After completing antibody treatment (5 monthly cycles), patients could receive vaccine. Event‐free survival (EFS) and overall survival (OS) were calculated from start of naxitamab + nGM‐CSF. Forty‐three patients received 157 cycles. Acute toxicities were generally manageable, allowing outpatient treatment. Stepped‐up dosing and extended administration of GM‐CSF had no associated toxicity, hematological or otherwise. Human anti‐human antibody developed in 5/43 (12%) patients. Thirty‐four (79%) patients received the vaccine; 9 did not due to relapse ( n = 4) and parental choice ( n = 5). EFS/OS rates at 24 months were 88%/95% and at 36 months were 80%/95%. Naxitamab + nGM‐CSF is a good option to consolidate first CR of HR‐NB patients, including those who did not undergo MAT.