Poster Presentation Advances in Neuroblastoma Research Congress 2016

Dinutuximab combined with chemotherapy in patients with multiply relapsed/refractory high risk neuroblastoma (HR-NBL) (#208)

Angela Cha 1 , Shahab Asgharzadeh 1 , Scarlett Czarnecki 1 , Hollie Lai 2 , Hiro Shimada 3 , Robert Seeger 1 , Araz Marachelian 1
  1. Division of Hematology, Oncology and Blood & Marrow Transplantation, Children's Hospital Los Angeles- University of Southern California, Los Angeles, CA, USA
  2. Department of Radiology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA
  3. Department of Pathology, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA

Background: Dinutuximab is part of standard upfront therapy for patients with HR-NBL. Conventional chemotherapy with immunotherapy has successfully been administered to patients with first relapse/refractory neuroblastoma but limited data exists on efficacy in patients resistant to multiple prior therapies.

 

Methods: Patients with HR-NBL with refractory/relapsed disease enrolled on NANT biology study and treated with dinutuximab concurrently with chemotherapy at Children’s Hospital Los Angeles were reviewed. Disease and treatment history, adverse events, and response per NANT criteria v1.2 were analyzed.  

 

Results: Six HR-NBL patients (refractory n=2, relapse n=4) were identified (table 1). Monthly cycles of dinutuximab (17.5mg/m2/dose), with either combination of irinotecan (50mg/m2/day) and temozolamide (100mg/m2/day) or combination of cyclophosphamide (250mg/m2/day) and topotecan (0.75mg/m2/dose), followed by 7-14 days of GMCSF were administered. No serious adverse events, including lack of fever or neutropenia, were noted despite limited marrow reserve. Complete remission (CR) was observed in 2/6, partial response (PR) in 3/6, and minor response (MR) in 1/6. Two patients with target lesions achieved CR. MIBG response showed 2/6 CR, 3/6 PR, and 1/6 stable disease. All patients with evaluable bone marrow (BM) achieved CR (n=5); including patients achieving first ever tumor-negative BM (n=3) from diagnosis or since relapse (n=2). Elevated catecholamines normalized within a week of therapy when elevated.

 

Conclusions: Combination chemotherapy and dinutuximab is well tolerated. The exceptional response rate (5 out of 6 with PR/CR) in patients resistant to multiple prior therapies is encouraging and this approach warrants further use and study in this cohort of patients.

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