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

Abstract

Background 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). Procedure Seventy‐three consecutive patients with HR‐NB (stage M at age >18 months 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 5 days at 250 μg/m2/day (days −4 to 0), followed by naxitamab + SC GM‐CSF for 5 days at 500 μg/m2/day (days 1–5). Naxitamab was infused over 30 minutes at 3 mg/kg/day, days 1, 3, and 5, outpatient. Results 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. Conclusions Consolidation with naxitamab and GM‐CSF resulted in excellent survival rates for HR‐NB patients in CR.

How we approach the treatment of patients with high-risk neuroblastoma with naxitamab: experience from the Hospital Sant Joan de Déu in Barcelona, Spain

“…infusion over 30-60 min in the outpatient setting—GM-CSF is omitted if the absolute neutrophil count is above 20 000/μL. 13 , 17…”

“…Studies are also investigating the potential of these agents to consolidate treatment response to chemotherapy. 12 , 13 Naxitamab [humanized 3f8 (hu3f8)], a humanized anti-GD2 immunotherapy, received ‘orphan’ designation from the United States Food and Drug Administration (FDA) in 2013 14 and from the European Medicines Agency in 2018 15 ; in 2018, it was also assigned ‘breakthrough therapy’ designation by the FDA. 16 Naxitamab in combination with sargramostim [recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF)] was approved by the FDA in November 2020 for the treatment of pediatric patients ≥1 year of age and adults with relapsed and/or refractory (R/R) HR neuroblastoma in the bone or BM who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy.…”

Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma

“…Significant differences in EFS can be found between patients with first and second CR (p = 0.0029). The pattern of relapse was mainly isolated organ (75%), mostly bone (54%) [69]. How to achieve a better remission rate is the challenge.…”

Monoclonal Antibodies (mAbs) Approved for Cancer Treatment in the 2020s

“…Naxitamab is a humanized GD2-specific monoclonal antibody (also known as naxitamab-gqgk or hu3F8), which in November 2020, was approved for the treatment of patients (≥ 1-year-old) with R/R neuroblastoma (either in the bone or bone marrow), in conjunction with GM-CSF, who have previously undergone prior treatments and have responded to it in the form of partial responses, stable diseases, or even minor responses (43)(44)(45)(46)(47)(48). Naxitamab, under the tradename Danyelza TM , was approved for medical use based on the findings of a phase 1/2 and a phase 2 clinical trial (clinical trial identifier: NCT01757626 and NCT03363373, respectively) in the both of which the safety and clinical efficacy of Naxitamab were investigated in R/R patients with high-risk neuroblastoma (43,46).…”