TY - JOUR
T1 - A Phase II trial of Hu14.18K322A in combination with induction chemotherapy in children with newly diagnosed high-risk neuroblastoma
AU - Furman, Wayne L.
AU - Federico, Sara M.
AU - McCarville, Mary Beth
AU - Shulkin, Barry L.
AU - Davidoff, Andrew M.
AU - Krasin, Matthew J.
AU - Sahr, Natasha
AU - Sykes, April
AU - Wu, Jianrong
AU - Brennan, Rachel C.
AU - Bishop, Michael William
AU - Helmig, Sara
AU - Stewart, Elizabeth
AU - Navid, Fariba
AU - Triplett, Brandon
AU - Santana, Victor M.
AU - Bahrami, Armita
AU - Anthony, Gwendolyn
AU - Yu, Alice L.
AU - Hank, Jacquelyn
AU - Gillies, Stephen D.
AU - Sondel, Paul M.
AU - Leung, Wing H.
AU - Pappo, Alberto S.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Purpose:We sought to evaluate whether combining ahumanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoinwere then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123Imetaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.
AB - Purpose:We sought to evaluate whether combining ahumanized antidisialoganglioside mAb (hu14.18K322A) with induction chemotherapy improves early responses and outcomes in children with newly diagnosed high-risk neuroblastoma. Patients and Methods: We conducted a prospective nonrandomized, single-arm, two-stage, phase II clinical trial. Six courses of induction chemotherapy were coadministered with hu14.18K322A and followed with granulocyte-macrophage colony-stimulating factor (GM-CSF) and low-dose IL2. Consolidation was performed with a busulfan/melphalan preparative regimen. An additional course of hu14.18K322A was administered with parent-derived natural killer cells, when available, during consolidation. Hu14.18K322A, GM-CSF, IL2, and isotretinoinwere then administered. Secondary outcomes included reduced tumor volume and semiquantitative 123Imetaiodobenzylguanidine scoring [i.e., Curie scores (CS)] at the end of induction. Results: Forty-two patients received hu14.18K322A and induction chemotherapy. This regimen was well tolerated, with continuous-infusion narcotics adjusted to patient tolerance. Partial responses (PR) or better after the first two chemoimmunotherapy courses occurred in 32 patients [76.2%; 95% confidence interval (CI), 60.6-88.0]. This was accompanied by primary tumor volume reductions (median, -76%; range, -100% to 5%). Of 35 patients with stage IV disease who completed induction, 31 had end-of-induction CSs of 2 or less. No patients experienced progression during induction. Two-year event-free survival (EFS) was 85.7% (95% CI, 70.9-93.3). Conclusions: Adding hu14.18K322A to induction chemotherapy produced early PR or better in most patients, reduced tumor volumes, improved CSs at the end of induction, and yielded an encouraging 2-year EFS. These results, if validated in a larger study, may change the standard of care for children with high-risk neuroblastoma.
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UR - http://www.scopus.com/inward/citedby.url?scp=85074446029&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-19-1452
DO - 10.1158/1078-0432.CCR-19-1452
M3 - Article
C2 - 31601569
AN - SCOPUS:85074446029
SN - 1078-0432
VL - 25
SP - 6320
EP - 6328
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 21
ER -
