NYMC Faculty Publications
Ibrutinib Plus RICE or RVICI for Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma in Children and Young Adults: SPARKLE Trial
Author Type(s)
Faculty
DOI
10.1182/bloodadvances.2022008802
Journal Title
Blood Advances
First Page
602
Last Page
610
Document Type
Article
Publication Date
2-28-2023
Department
Pediatrics
Abstract
Part 1 results of the open-label, randomized, global phase 3 SPARKLE trial supported continued assessment of ibrutinib with either modified rituximab, ifosfamide, carboplatin, and etoposide (RICE) or rituximab, vincristine, ifosfamide, carboplatin, idarubicin, and dexamethasone (RVICI) in pediatric patients with relapsed/refractory (R/R) mature B-cell non-Hodgkin lymphoma (B-NHL). We report final results of Part 2 evaluating the efficacy of ibrutinib plus RICE or RVICI vs RICE/RVICI alone. Patients aged 1 to 30 years (initial diagnosis <18 years) were randomized 2:1 to receive ibrutinib with or without RICE/RVICI. Primary endpoint was event-free survival (EFS) based on independent committee-confirmed events. Fifty-one patients were enrolled. Median age was 15 years; Burkitt lymphoma, Burkitt leukemia, and Burkitt-like lymphoma (total: 45%) and diffuse large B-cell lymphoma/primary mediastinal B-cell lymphoma (51%) were the most common subtypes. At the preplanned interim analysis, median EFS was 6.1 vs 7.0 months with ibrutinib plus RICE/RVICI vs RICE/RVICI, respectively (hazard ratio, 0.9; 90% confidence interval, 0.5-1.6; P = .387); further enrollment was ceased. With ibrutinib plus RICE/RVICI vs RICE/RVICI, median overall survival was 14.1 vs 11.1 months, overall response rate was 69% vs 81%, and 46% vs 44% proceeded to stem cell transplantation. In both treatment arms, 100% of patients experienced grade ≥3 treatment-emergent adverse events. No EFS benefit was seen with ibrutinib. Salvage was generally poor in patients who received prior rituximab, regardless of treatment arm. No new safety signals were observed. Ibrutinib exposure in pediatric patients fell within the target range of exposure in adults. Trial is registered on www.clinicaltrials.gov (NCT02703272).
Recommended Citation
Burke, G. A., Vinti, L., Kabickova, E., Beishuizen, A., Tacyildiz, N., Uyttebroeck, A., Kang, H. J., Luisi, F., Minard-Colin, V., Burkhardt, B., Tamegnon, M., Sun, S., Curtis, M., Deshpande, S., Nottage, K., Howes, A., Srinivasan, S., Bhojwani, D., Norris, R., & Cairo, M. (2023). Ibrutinib Plus RICE or RVICI for Relapsed/Refractory Mature B-Cell Non-Hodgkin Lymphoma in Children and Young Adults: SPARKLE Trial. Blood Advances, 7 (4), 602-610. https://doi.org/10.1182/bloodadvances.2022008802