TY - JOUR
T1 - Progression-Free Survival and Patterns of Response in Patients with Relapsed High-Risk Neuroblastoma Treated with Irinotecan/Temozolomide/Dinutuximab/Granulocyte-Macrophage Colony-Stimulating Factor
AU - Lerman, Benjamin J.
AU - Li, Yimei
AU - Carlowicz, Cecilia
AU - Granger, Meaghan
AU - Cash, Thomas
AU - Sadanand, Arhanti
AU - Somers, Katherine
AU - Ranavaya, Aeesha
AU - Weiss, Brian D.
AU - Choe, Michelle
AU - Foster, Jennifer H.
AU - Pinto, Navin
AU - Morgenstern, Daniel A.
AU - Rafael, Margarida Simão
AU - Streby, Keri A.
AU - Zeno, Rachel N.
AU - Mody, Rajen
AU - Yazdani, Sahr
AU - Desai, Ami V.
AU - Macy, Margaret E.
AU - Shusterman, Suzanne
AU - Federico, Sara M.
AU - Bagatell, Rochelle
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2023/1/20
Y1 - 2023/1/20
N2 - PURPOSEAlthough chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy.PATIENTS AND METHODSPatients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria.RESULTSOne hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF.CONCLUSIONApproximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.
AB - PURPOSEAlthough chemoimmunotherapy is widely used for treatment of children with relapsed high-risk neuroblastoma (HRNB), little is known about timing, duration, and evolution of response after irinotecan/temozolomide/dinutuximab/granulocyte-macrophage colony-stimulating factor (I/T/DIN/GM-CSF) therapy.PATIENTS AND METHODSPatients eligible for this retrospective study were age < 30 years at diagnosis of HRNB and received ≥ 1 cycle of I/T/DIN/GM-CSF for relapsed or progressive disease. Patients with primary refractory disease who progressed through induction were excluded. Responses were evaluated using the International Neuroblastoma Response Criteria.RESULTSOne hundred forty-six patients were included. Tumors were MYCN-amplified in 50 of 134 (37%). Seventy-one patients (49%) had an objective response to I/T/DIN/GM-CSF (objective response; 29% complete response, 14% partial response [PR], 5% minor response [MR], 21% stable disease [SD], and 30% progressive disease). Of patients with SD or better at first post-I/T/DIN/GM-CSF disease evaluation, 22% had an improved response per International Neuroblastoma Response Criteria on subsequent evaluation (13% of patients with initial SD, 33% with MR, and 41% with PR). Patients received a median of 4.5 (range, 1-31) cycles. The median progression-free survival (PFS) was 13.1 months, and the 1-year PFS and 2-year PFS were 50% and 28%, respectively. The median duration of response was 15.9 months; the median PFS off all anticancer therapy was 10.4 months after discontinuation of I/T/DIN/GM-CSF.CONCLUSIONApproximately half of patients receiving I/T/DIN/GM-CSF for relapsed HRNB had objective responses. Patients with initial SD were unlikely to have an objective response, but > 1 of 3 patients with MR/PR on first evaluation ultimately had complete response. I/T/DIN/GM-CSF was associated with extended PFS in responders both during and after discontinuation of treatment. This study establishes a new comparator for response and survival in patients with relapsed HRNB.
UR - http://www.scopus.com/inward/record.url?scp=85146484535&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85146484535&partnerID=8YFLogxK
U2 - 10.1200/JCO.22.01273
DO - 10.1200/JCO.22.01273
M3 - Article
C2 - 36206505
AN - SCOPUS:85146484535
SN - 0732-183X
VL - 41
SP - 508
EP - 516
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -