Background: The literature on MYCN-amplified stage 2/3 neuroblastoma is limited because this high-risk subset is uncommon. Its prognosis improved with ASCT. Reports on anti-GD2 immunotherapy do not provide details on this entity. We now present our experience since 2000 when anti-GD2 antibody 3F8/GM-CSF+isotretinoin became routine. ASCT was used 2000-2003 at our center but not thereafter, though patients transplanted elsewhere remained eligible for 3F8/GM-CSF.
Methods: This report on MYCN-amplified stage 2/3 has two components. Part 1 covers an unselected series of 24 consecutive newly-diagnosed patients treated with dose-intensive induction chemotherapy. Part 2 concerns 3F8/GM-CSF+isotretinoin as consolidation of first complete remission (CR), including 20 (15 non-ASCT and 5 ASCT patients) of the aforementioned 24 newly-diagnosed patients, plus 6 patients referred post-ASCT. Consolidation included local radiotherapy.
Results: Part 1: 21/24 (88%) newly-diagnosed patients achieved CR with induction; 20 received consolidation but one CR patient did not (social reasons) and eventually died of progressive disease (PD). Three patients had PD with induction and died early. At 5 years post-diagnosis, these 24 patients had EFS/OS 67%/77%. Part 2: Regarding consolidation with 3F8/GM-CSF+isotretinoin, the 15 non-ASCT patients include 12 relapse-free 12-151 (median 40) months from diagnosis and two who relapsed but remain in 2nd CR at 24 and 84 months post-relapse (their salvage included 3F8/GM-CSF+isotretinoin again). These 15 non-ASCT patients had EFS/OS 72%/92% at five years from start of 3F8. Of 11 ASCT patients, 10 remain relapse-free 75-204 (median 164) months from diagnosis, with EFS/OS 91%/91% at 5 years from start of 3F8. There were no significant differences in EFS/OS between non-ASCT and ASCT cohorts (p=.34/.92). Minimal residual disease (bone marrow) was detected in only 3 patients, cleared with 3F8/GM-CSF, and did not predict relapse.
Conclusions: This subset has a good prognosis with contemporary multi-modality therapy, even without ASCT. Repeating anti-GD2 immunotherapy post-relapse may be warranted.