MedicalResearch.com Interview with:
Wayne L. Furman, MD
Department of Oncology
Jude Children’s Research Hospital
Memphis, TN 38105-3678
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Furman: Despite improvement in 2-yr EFS from 46% to 66% with the inclusion of dinutuximab, a monoclonal antibody that recognizes a glycoprotein on neuroblasts called ‘GD2’ (disialoganglioside), more than one-third of children with high-risk neuroblastoma still are not cured. Therefore novel therapeutic approaches are needed for this subset of patients. The clinical evaluation of various anti-GD 2 monoclonal antibodies in children with neuroblastoma has been exclusively focused on treatment of patients after recovery from consolidation, in a state of ‘minimal residual disease’. This is because traditionally chemotherapy has been thought to be too immunosuppressive to combine with monoclonal antibodies. However recent studies suggest, even in the setting of “bulky” solid tumors, the combination of chemotherapy with monoclonal antibodies can enhance the effectiveness of the antibodies. First, chemotherapy can increase the efficacy of antibodies by depleting cells of the immune system that suppress immune function. Also chemotherapy-induced tumor cell death can trigger tumor antigen release, uptake by antigen processing cells and an enhanced antitumor immune response. There is also data that anti-GD2 monoclonal antibodies can suppress tumor cell growth independent of immune system involvement. Furthermore anti-GD2 monoclonal antibodies and chemotherapy have non-overlapping toxicities. All of these reasons were good reasons to evaluate the addition of a novel anti-GD2 monoclonal antibody, called hu14.18K322A, to chemotherapy, outside the setting of minimal residual disease, in children with newly diagnosed children with high-risk neuroblastoma.
MedicalResearch.com: What are the main findings?
Dr. Furman: The addition of an anti-GD2 monoclonal antibody (hu14.18K322A) to induction chemotherapy resulted in improved response, compared to children who got identical chemotherapy, without an anti-GD2 monoclonal antibody. Eighty percent of patients who received hu14.14K322A in addition to the standard chemotherapy had a response to therapy compared to a 40% response in a historical control of patients who received standard chemotherapy only.
MedicalResearch.com: What should readers take away from your report?
Dr. Furman: Adding hu14.18K322A to standard chemotherapy in patients with newly diagnosed high-risk neuroblastoma is well tolerated and shows a signal of activity by improved early response. These results are very early and only in a small number of patients. It still remains to be determined if this early ‘shrinkage’ of tumors will result in more cures. This will take several more years to determine.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Furman:: We need to treat more patients with this approach and follow them longer to see if this does translate into more cures. Also the only ‘anti-GD2’ monoclonal antibody approved by the FDA is called dinutuximab. Dinutuximab needs to be given with induction chemotherapy to newly diagnosed children with high-risk neuroblastoma, to see if these results also hold true with this antibody or if they are unique to the anti-GD2 antibody used in NB2012, called hu14.18K322A.
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Citation: Presented at the 2016 ASCO Annual Meeting
Improved clinical responses with the concomitant use of an anti-GD2 monoclonal antibody and chemotherapy in newly diagnosed children with high-risk neuroblastoma Preliminary results of a phase II study.
Abstract No: 10501
J Clin Oncol 34, 2016 (suppl; abstr 10501)
Author(s): Wayne Lee Furman, Sara Michele Federico, Mary B McCarville, Andrew M. Davidoff, Matthew J. Krasin, Jianrong Wu, Rachel Christine Brennan, Michael William Bishop, Victor M. Santana, Armita Bahrami, Gwendolyn Anthony, Stephen D Gillies, Paul M. Sondel, Wing H. Leung, Alberto S. Pappo; St. Jude Children’s Research Hospital, Memphis, TN; Provenance Biopharmaceuticals Corporation, Carlisle, ME; University of Wisconsin, Madison, WI
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