Background: The COG conducted a groupwide study of a Busulfan/Melphalan (BuMel) myeloablative regimen in patients with newly diagnosed, high-risk neuroblastoma (ANBL12P1). Previously used in SIOP-EN studies, this is the first trial using BuMel following a COG induction platform. The primary objective was regimen-related toxicity, with a specific focus on pulmonary and hepatic events.
Methods: Five cycles of induction were administered, followed by intravenous busulfan (daily, days -6 to -3), melphalan (140mg/m2, day -1) and stem cell rescue. Age and weight based dosing were used for busulfan administration. First dose busulfan pharmacokinetics were mandated and adjustments made to target an AUC
Results: Between 4/2013 and 4/2015, 150 patients were enrolled. One hundred thirteen patients were evaluable for end-induction response assessment, with 27 (25%) CR, 27 (24%) VGPR and 39 (35%) PR, for an overall response rate of 82%. At the time of consolidation, 101 patients are evaluable for toxicity. The incidence of unacceptable pulmonary toxicity was 3.0% (n = 3), SOS 5.9% (n = 6), and combined hepato-pulmonary toxicity 8.9% (N = 9) during consolidation (days 0–28). There were 0 toxic deaths during consolidation. For all subjects (n=98), the median busulfan AUC was 3554 (range: 2360-4555) micromole/liter*minute, with a median AUC of 4558 (range: 3462-5189) micromole/liter*minute for those developing SOS (n =6) and 3232 (range: 3010-5037) micromole/liter*minute for those developing severe pulmonary toxicity (n= 3).
Conclusion: BuMel following COG induction regimen is well tolerated with acceptable pulmonary and hepatic toxicity in high-risk neuroblastoma.