Background: In an international trial, the humanized anti-GD2 antibody naxitamab+GM-CSF was effective against chemo-resistant HR-NB, leading to approval by the Food and Drug Administration. We subsequently modified GM-CSF dosing based on a shortened priming period and pharmacokinetics showing prolonged T½ of naxitamab. We investigated safety and efficacy of naxitamab plus GM-CSF administered by a novel schedule in HR-NB patients treated in 1^st CR (Group 1) or with primary refractory disease in bones and/or bone marrow (BM) (Group 2). Methods: Immunotherapy was administered q1-2 months up to 5 cycles in Group 1 and ≥5 cycles after major responses in Group 2. Naxitamab was infused intravenously (30-90”) on days 1/Monday-3/Wednesday-5/Friday (i.e., 3 doses/cycle), 3mg/kg/infusion (9mg/kg/cycle, i.e., ~270mg/m²/cycle). Previously, priming doses of GM-CSF 250µg/m²/day were subcutaneously-administered x5 (days -4 to 0), followed by a step-up to 500µg/m²/day x5 (days 1-to-5), but now priming doses were x3 days (days -2 to 0 [Friday-Saturday-Sunday]) and stepped-up dosing was x7 (days 1-to-7 [Monday-to-Sunday]), i.e., through 2 days after the last dose of naxitamab. Patients did not receive isotretinoin. Follow-up was from start of naxitamab through 1/15/23. Results: From 2/22/2021-to-12/15/22, 59 patients (32 Group 1, 27 Group 2) received 1-10 (median 5) cycles, total 250. No unexpected toxicities occurred. No patient had to discontinue GM-CSF. Treatment was outpatient, except 3 patients with hypertension. Cycles were aborted because of viral symptoms (n=3), suspected small bowel obstruction (n=3), hypoxia (n=2), and hyperbilirubinemia (n=1). Four patients received only ½ of dose 1 in cycle 1 because of agitation or hypotension. In Group 1, 4/32 patients relapsed at 4-5 months while 28 patients remain in CR at 1+-to-22+ (median 15+) months. In Group 2, disease sites and responses were: BM alone (n=7): CR in 6 (1 later relapsed); MIBG alone (Curie scores 1-11) (n=8): 1 partial response, 1 progressive disease, 2 stable (1 later relapsed), 4 non-evaluable because of radiotherapy; MIBG (Curie scores 1-26) and BM(+) (n=12): 7 CR (3 later relapsed), 4 PR, 1 stable disease (subsequently progressed). Conclusions: This large experience confirms that the new schedule is safe and, despite short follow-up, appears as effective as the prior schedule.