Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults

Paul Harker-Murray, Christine Mauz-Körholz, Thierry Leblanc, Maurizio Mascarin, Gérard Michel, Stacy Cooper, Auke Beishuizen, Kasey J. Leger, Loredana Amoroso, Salvatore Buffardi, Charlotte Rigaud, Bradford S. Hoppe, Julie Lisano, Stephen Francis, Mariana Sacchi, Peter D. Cole, Richard A. Drachtman, Kara M. Kelly, Stephen Daw*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)
18 Downloads (Pure)

Abstract

Children, adolescents, and young adults (CAYA) with relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) without complete metabolic response (CMR) before autologous hematopoietic cell transplantation (auto-HCT) have poor survival outcomes. CheckMate 744, a phase 2 study for CAYA (aged 5-30 years) with R/R cHL, evaluated a risk-stratified, response-adapted approach with nivolumab plus brentuximab vedotin (BV) followed by BV plus bendamustine for patients with suboptimal response. Risk stratification was primarily based on time to relapse, prior treatment, and presence of B symptoms. We present the primary analysis of the standard-risk cohort. Data from the low-risk cohort are reported separately. Patients received 4 induction cycles with nivolumab plus BV; those without CMR (Deauville score >3, Lugano 2014) received BV plus bendamustine intensification. Patients with CMR after induction or intensification proceeded to consolidation (high-dose chemotherapy/auto-HCT per protocol). Primary end point was CMR any time before consolidation. Forty-four patients were treated. Median age was 16 years. At a minimum follow-up of 15.6 months, 43 patients received 4 induction cycles (1 discontinued), 11 of whom received intensification; 32 proceeded to consolidation. CMR rate was 59% after induction with nivolumab plus BV and 94% any time before consolidation (nivolumab plus BV ± BV plus bendamustine). One-year progression-free survival rate was 91%. During induction, 18% of patients experienced grade 3/4 treatment-related adverse events. This risk-stratified, response-adapted salvage strategy had high CMR rates with limited toxicities in CAYA with R/R cHL. Most patients did not require additional chemotherapy (bendamustine intensification). Additional follow-up is needed to confirm durability of disease control. This trial was registered at www.clinicaltrials.gov as #NCT02927769.

Original languageEnglish
Pages (from-to)2075-2084
Number of pages10
JournalBlood
Volume141
Issue number17
DOIs
Publication statusPublished - 27 Apr 2023

Bibliographical note

Funding Information:
Professional medical writing and editorial support were provided by Adam Gill and Jane Cheung, Caudex, funded by Bristol Myers Squibb . This work was supported by Bristol Myers Squibb , in collaboration with Seagen. Direct funding was provided by Bristol Myers Squibb through the joint financial support of Bristol Myers Squibb and Seagen .

Publisher Copyright:
© 2023 The American Society of Hematology

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