Ibrutinib plus RICE or RVICI for relapsed/refractory mature B-cell non-Hodgkin lymphoma in children and young adults: SPARKLE trial

G. A. Amos Burke*, Luciana Vinti, Edita Kabickova, Auke Beishuizen, Nurdan Tacyildiz, Anne Uyttebroeck, Hyoung Jin Kang, Flavio Luisi, Véronique Minard-Colin, Birgit Burkhardt, Monelle Tamegnon, Steven Sun, Madeliene Curtis, Sanjay Deshpande, Kerri Nottage, Angela Howes, Srimathi Srinivasan, Deepa Bhojwani, Robin Norris, Mitchell Cairo

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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

Original languageEnglish
Pages (from-to)602-610
Number of pages9
JournalBlood advances
Volume7
Issue number4
DOIs
Publication statusPublished - 20 Feb 2023

Bibliographical note

Funding Information:
Conflicts-of-interest disclosure: G.A.A.B.’s institution received consultancy fees from Janssen, Merck, Takeda, Roche, and Oxford Immune Algorithmics. H.J.K. participated on an advisory board for Amgen, Novartis, and Cartexell and received research funding from Amgen. F.L.’s institution received consultancy fees from Janssen. V.M-C.’s institution received consultancy fees from Janssen,

Funding Information:
This study was funded by Janssen Research and Development. The authors thank Xavier Woot de Trixhe for his contributions to the study and all of the patients and their families who were included in this analysis. Writing assistance was provided by Ian Phillips of Parexel, and was funded by Janssen Research and Development.

Publisher Copyright:
© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

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