Naxitamab and GM-CSF for consolidation of high-risk neuroblastoma (HR-NB) patients in complete remission.

Abstract

10021 Background: Naxitamab was recently approved in the US in combination with GM-CSF for the treatment of patients (pts) with relapse/refractory HR-NB in the bone/bone marrow who have demonstrated a partial response (PR), minor response (MR), or stable disease (SD) to prior therapy. Here we describe the use of 5 cycles of naxitamab and GM-CSF through compassionate use for consolidation of HR-NB pts in first or subsequent complete remission (CR). Methods: HR-NB pts in CR (first or subsequent) after initial multimodal induction treatment were eligible. Disease status was assessed at study entry by histology of BM biopsies/aspirates obtained from bilateral posterior and bilateral anterior iliac crests, I-MIBG SPECT scan, and whole body MRI. FDG-PET was used for MIBG non-avid cases at diagnosis. Quantitative reverse transcription-polymerase chain reaction was used to assess MRD in pooled heparinized BM aspirates. Disease response was defined according to the revised INRC. Four BM aspirates and 123I-MIBG SPECT scan or FDG-PET scans were performed after cycles 2 and 5 and every 3 months thereafter for one year in all pts to assess response. Naxitamab was administered over ≥30 min in the outpatient setting on Days 1, 3 and 5 at 3.0 mg/kg/infusion (9.0 mg/kg/cycle) in combination with GM-CSF at 250 ug/m2/day on Days -4 to 0 and at 500 ug/m2/day on days 1 to 5. Treatment cycles were repeated every 4 weeks. Survival curves were built from the time of naxitamab treatment initiation by Kaplan-Meier methods and compared using the log-rank test. Results: From June 2017 to November 30 2020, 73 pts were treated: 55 (75%) in first CR and 18 (25%) in second or more CR. Majority of pts were MYCN non-amplified (n=56, 77%), all stage 4, median age at treatment initiation 4.5 years. 61 (84%) pts had received >5 cycles of induction chemotherapy; 22 (30%) high-dose chemotherapy and autologous stem cell transplant (ASCT); and 36 (49%) radiotherapy before receiving naxitamab. 58 (79.5%) pts completed naxitamab therapy, 53 (73%) in continued CR. 10 (14%) pts relapsed during treatment and 5 (7%) had grade 4 toxicities: 2 apnea related to naxitamab; and 2 non-related: 1 opioid related chest rigidity syndrome and 1 stroke. 3-y event-free-survival (EFS) for all pts is 58% [95% CI, 43.5; 78.4], 74% for first CR and 19% for second or more CR (p=0.0029). 3-y OS for the whole group is 82% [95% CI, 66.8; 100.0], 92% for first CR and 66% for second or more CR pts (p=0.18). Univariate Cox models for CR group, MYCN status, number of chemotherapies, ASCT, radiotherapy, MRD, and age showed significant p value only for prior relapse as predictor of EFS (p=0.047). Conclusions: Naxitamab for HR-NB pts in CR provided excellent 3-y OS rates regardless of previous management. The only predictor for relapse is prior history of recurrence.