Naxitamab

Myeloablative therapy (MAT) is included in high‐risk neuroblastoma (HR‐NB) treatment programs of the Children's Oncology Group (COG) and the Societe Internationale d'Oncologie Pediatrique Europe Neuroblastoma (SIOPEN), but not at Memorial Sloan Kettering Cancer Center (MSK). COG and SIOPEN programs achieved 3–5‐year event‐free survival rates of ~50%–60%, similar to the MSK experience without MAT which involved patients treated with COG or MSK induction and anti‐G D2 mAb murine‐3F8 + granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). We now present the first report on rapid COJEC without MAT. This retrospective study covers HR‐NB patients who received rapid COJEC but not MAT and had no prior progressive disease (PD) when referred to MSK during the era of availability of anti‐G D2 mAb naxitamab. The 28 subjects were diagnosed 1/2017–6/2023. Post‐COJEC, 10 had no distant disease (Group 1) and 18 had persistence of metastases (Group 2). Group 1 patients had resection of primary tumors and received 1–2 cycles of HR‐NB regimens (cyclophosphamide‐topotecan ± vincristine), local radiotherapy, and naxitamab + GM‐CSF; 9 also received anti‐NB vaccine. All 10 remain event‐free at median 3.5+ years post‐diagnosis. Group 2 patients received second‐line therapy post‐COJEC, including high‐dose cyclophosphamide + topotecan ± vincristine or cyclophosphamide + doxorubicin + vincristine. Treatment after all chemotherapy included naxitamab + GM‐CSF ± irinotecan‐temozolomide. Thirteen received vaccine. Twelve remain relapse‐free at median 2.4+ years post‐diagnosis, including 3 who developed secondary neoplasms—myelodysplastic syndrome ( n  = 2, successfully treated) or thyroid carcinoma. Six developed PD (four are again in complete remission and two died of NB). Avoiding MAT after rapid COJEC does not appear to adversely affect outcome compared to rapid COJEC + MAT.

Approved treatments for patients with refractory and/or relapsed (R/R) high-risk (HR) neuroblastoma are limited, and there is a need for new treatment combinations. In this case series, 4 patients were treated with the anti-GD2 monoclonal antibody naxitamab and granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with cyclophosphamide and topotecan between August 2021 and December 2022. This combined chemoimmunotherapy regimen was well tolerated in these heavily pretreated patients with R/R HR neuroblastoma who had few treatment options and overall poor prognoses.