A phase II trial of naxitamab plus stepped‐up dosing of GM ‐ CSF for patients with high‐risk neuroblastoma in second or later complete remission

Abstract Relapse of high‐risk neuroblastoma (HR‐NB) poses a challenge to cure. Increasing numbers of HR‐NB patients achieve post‐relapse complete remission (CR) because close monitoring can detect localized disease and novel effective salvage therapies have emerged. We report outcome with immunotherapy using the anti‐G D2 monoclonal antibody (mAb) naxitamab and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) for consolidation of second or later CR in a phase II trial (Clinicaltrials.gov NCT01757626). Cycles included GM‐CSF 250 μg/m 2 /day on days −4‐to‐0 and increased to 500 μg/m 2 /day on days +1‐to‐5, and 3 doses of naxitamab infused (30‐to‐90 min) on days +1/+3/+5, 3 mg/kg/infusion (9 mg/kg/cycle, i.e., ~270 mg/m 2 /cycle). Cycles were monthly ×5. Clinical factors assessed regarding prognosis were: MYCN amplification; localized versus widespread prior relapse; 1 versus ≥2 prior relapse(s); previous treatment with anti‐G D2 mAb; and time from diagnosis to 1st relapse. Sixty patients were enrolled after 1 ( n = 42) or ≥2 ( n = 18) prior relapse(s); 27 (45%) had MYCN amplification. Progression‐free survival (PFS) rates at 2/5 years were 55%/50%. Prior treatment with naxitamab and prior widespread relapse had significant negative impacts on PFS. Post‐protocol patients in CR routinely received an investigational anti‐NB vaccine. Two other patients, both with 1 prior relapse, took DFMO. Naxitamb+GM‐CSF is a good option to consolidate post‐relapse CR of HR‐NB. The encouraging long‐term outcome cannot be attributed solely to naxitamab+GM‐CSF given post‐protocol therapies.