TY - JOUR
T1 - Eflornithine as Postimmunotherapy Maintenance in High-Risk Neuroblastoma
T2 - Externally Controlled, Propensity Score-Matched Survival Outcome Comparisons
AU - Oesterheld, Javier
AU - Ferguson, William
AU - Kraveka, Jacqueline M.
AU - Bergendahl, Genevieve
AU - Clinch, Thomas
AU - Lorenzi, Elizabeth
AU - Berry, Don
AU - Wada, Randal K.
AU - Isakoff, Michael S.
AU - Eslin, Don E.
AU - Brown, Valerie I.
AU - Roberts, William
AU - Zage, Peter
AU - Harrod, Virginia L.
AU - Mitchell, Deanna S.
AU - Hanson, Derek
AU - Saulnier Sholler, Giselle L.
N1 - Publisher Copyright:
© American Society of Clinical Oncology.
PY - 2024/1/1
Y1 - 2024/1/1
N2 - PURPOSELong-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion of immunotherapy was investigated previously in a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free survival (EFS) and overall survival (OS) compared with historical rates in a phase III trial (Children Oncology Group ANBL0032; ClinicalTrials.gov identifier: NCT00026312). Using patient-level data from ANBL0032 as an external control, we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance.PATIENTS AND METHODSNMTRC003B (2012-2016) enrolled patients with HRNB (N = 141) after standard up-front or refractory/relapse treatment who received up to 2 years of continuous treatment with oral DFMO (750 ± 250 mg/m2 twice a day). ANBL0032 (2001-2015) enrolled patients with HRNB postconsolidation, 1,328 of whom were assigned to dinutuximab (ch.14.18) treatment. Selection rules identified 92 NMTRC003B patients who participated in (n = 87) or received up-front treatment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who could have been eligible for NMTRC003B after immunotherapy, but did not enroll (the NO-DFMO/control group). The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients. Kaplan-Meier and Cox regression compared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on 11 baseline demographic and disease characteristics with exact matching on MYCN, and additional sensitivity analyses.RESULTSDFMO after completion of immunotherapy was associated with improved EFS (hazard ratio [HR], 0.50 [95% CI, 0.29 to 0.84]; P =.008) and OS (HR, 0.38 [95% CI, 0.19 to 0.76]; P =.007). The results were confirmed with propensity score-matched cohorts and sensitivity analyses.CONCLUSIONThe externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.
AB - PURPOSELong-term survival in high-risk neuroblastoma (HRNB) is approximately 50%, with mortality primarily driven by relapse. Eflornithine (DFMO) to reduce risk of relapse after completion of immunotherapy was investigated previously in a single-arm, phase II study (NMTRC003B; ClinicalTrials.gov identifier: NCT02395666) that suggested improved event-free survival (EFS) and overall survival (OS) compared with historical rates in a phase III trial (Children Oncology Group ANBL0032; ClinicalTrials.gov identifier: NCT00026312). Using patient-level data from ANBL0032 as an external control, we present new analyses to further evaluate DFMO as HRNB postimmunotherapy maintenance.PATIENTS AND METHODSNMTRC003B (2012-2016) enrolled patients with HRNB (N = 141) after standard up-front or refractory/relapse treatment who received up to 2 years of continuous treatment with oral DFMO (750 ± 250 mg/m2 twice a day). ANBL0032 (2001-2015) enrolled patients with HRNB postconsolidation, 1,328 of whom were assigned to dinutuximab (ch.14.18) treatment. Selection rules identified 92 NMTRC003B patients who participated in (n = 87) or received up-front treatment consistent with (n = 5) ANBL0032 (the DFMO/treated group) and 852 patients from ANBL0032 who could have been eligible for NMTRC003B after immunotherapy, but did not enroll (the NO-DFMO/control group). The median follow-up time for DFMO/treated patients was 6.1 years (IQR, 5.2-7.2) versus 5.0 years (IQR, 3.5-7.0) for NO-DFMO/control patients. Kaplan-Meier and Cox regression compared EFS and OS for overall groups, 3:1 (NO-DFMO:DFMO) propensity score-matched cohorts balanced on 11 baseline demographic and disease characteristics with exact matching on MYCN, and additional sensitivity analyses.RESULTSDFMO after completion of immunotherapy was associated with improved EFS (hazard ratio [HR], 0.50 [95% CI, 0.29 to 0.84]; P =.008) and OS (HR, 0.38 [95% CI, 0.19 to 0.76]; P =.007). The results were confirmed with propensity score-matched cohorts and sensitivity analyses.CONCLUSIONThe externally controlled analyses presented show a relapse risk reduction in patients with HRNB treated with postimmunotherapy DFMO.
UR - http://www.scopus.com/inward/record.url?scp=85180607252&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85180607252&partnerID=8YFLogxK
U2 - 10.1200/JCO.22.02875
DO - 10.1200/JCO.22.02875
M3 - Article
C2 - 37883734
AN - SCOPUS:85180607252
SN - 0732-183X
VL - 42
SP - 90
EP - 102
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 1
ER -
