Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission.

Abstract

Naxitamab is a humanized anti-disialoganglioside (GD2) monoclonal antibody approved for treatment of bone/bone marrow refractory high-risk neuroblastoma (HR-NB). Compassionate use (CU) expanded access program at Hospital Sant Joan de Deu permitted treatment of patients in complete remission (CR). We here report the survival, toxicity, and relapse pattern of patients in first or second CR treated with naxitamab and sargramostim (GM-CSF). Seventy-three consecutive patients with HR-NB (stage M at age >18months or MYCN-amplified stages L1/L2 at any age) were treated in first or second CR. Treatment comprised five cycles of subcutaneous (SC) GM-CSF for 5days at 250μg/m2 /day (days -4 to 0), followed by naxitamab + SC GM-CSF for 5days at 500μg/m2 /day (days 1-5). Naxitamab was infused over 30minutes at 3mg/kg/day, days 1, 3, and 5, outpatient. Fifty-five patients were in first CR and 18 in second CR. Seventeen patients had MYCN-amplified NB and 11 detectable minimal residual disease in the bone marrow. Fifty-eight (79.5%) patients completed therapy. Four (5%) experienced grade 4 toxicities and 10 (14%) early relapse. Three-year event-free survival (EFS) 58.4%, 95% CI=(43.5%, 78.4%) and overall survival (OS) 82.4%, 95% CI=(66.8%, 100%). First CR patients 3-year EFS 74.3%, 95% CI=(62.7%, 88.1%), and OS 91.6%, 95% CI=(82.4%, 100%). EFS is significantly different between first and second CR (p=.0029). The pattern of relapse is predominantly (75%) of an isolated organ, mainly bone (54%). Univariate Cox models show prior history of relapse as the only statistically significant predictor of EFS but not OS. Consolidation with naxitamab and GM-CSF resulted in excellent survival rates for HR-NB patients in CR.