A Phase II Trial of Naxitamab plus Stepped-up Dosing of GM-CSF for Patients with High-Risk Neuroblastoma in First Complete Remission

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PURPOSE: Naxitamab is a humanized form of the murine anti-GD2 mAb 3F8. In an international trial, naxitamab + GM-CSF was effective against chemoresistant high-risk neuroblastoma (HR-NB), leading to approval by the FDA. We now report results with patients in first complete remission (CR). PATIENTS AND METHODS: The primary objective of this phase II protocol 16-1643 (Clinicaltrials.gov NCT03033303) was to assess event-free survival of patients with HR-NB in first CR treated with naxitamab + GM-CSF plus isotretinoin. HR-NB was defined as MYCN-amplified disease (any age) or metastatic disease at age >18 months. Cycles of immunotherapy were administered monthly up to five cycles and comprised (i) subcutaneously administered priming doses of GM-CSF 250 μg/m2/day on days -4 to -0 (Wednesday-Sunday), followed by a step-up to 500 μg/m2/day on days +1 to +5 (Monday-Friday) and (ii) naxitamab infused intravenously (30-90") on days +1, +3, and +5 (Monday-Wednesday-Friday, i.e., three doses/cycle). The dosage of naxitamab was 3 mg/kg/infusion (9 mg/kg/cycle, i.e., ∼270 mg/m2/cycle). The dosage of isotretinoin was 160 mg/m2/day started after cycle 2, ×14 days/course, and ×6 courses. RESULTS: Fifty-nine patients with HR-NB (53 stage 4, 6 stage 3) were enrolled from February 2017 to July 2020. At 36 months, event-free/overall survival rates were 73%/93%, but 50 of 59 patients received after protocol treatment (vaccine and/or difluoromethylornithine). Six of 18 relapses were isolated in the central nervous system. Longer time from diagnosis to enrollment was a significantly adverse prognostic factor (P = 0.04). Twenty-one of 59 patients took no isotretinoin. Treatment was tolerable allowing outpatient administration. CONCLUSIONS: Naxitamab + GM-CSF is a good option to consolidate first CR of patients with HR-NB, including those who did not undergo autologous stem-cell transplantation. Efforts to prevent central nervous system relapse are warranted.

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