The combination of nivolumab plus brentuximab vedotin (BV) with risk-adapted intensification of BV plus bendamustine resulted in high complete metabolic response (CMR) rates among children and adolescents and young adults (CAYAs) with relapsed/refractory Hodgkin lymphoma (HL). In addition, the majority of patients did not require bendamustine intensification.

The phase 2 CheckMate 744 trial (ClinicalTrials.gov identifier: NCT02927769) comprised standard- and low-risk cohorts. Results of the standard-risk cohort of 44 patients was published in Blood.

All patients were treated with nivolumab plus BV induction for 4 cycles. Consolidation included nivolumab plus BV and, for patients who did not achieve CMR after induction, BV plus bendamustine. The primary endpoint was CMR any time before consolidation.


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The median age of the cohort was 16 years and 66% of patients were male. There were 55% of patients who had primary refractory HL and 32% whose disease relapsed between 3 to 12 months and 14% with relapse 12 months or longer after completing first-line treatment. None of the patients had previously received BV or undergone an autologous hematopoietic cell transplant. Bone marrow involvement was present among 11% of patients and stage IV disease was present at relapse among 36%.

Induction with nivolumab plus BV resulted in a CMR rate of 59%, which increased to 82% after 2 cycles of intensification with BV plus bendamustine, and 94% at any time before consolidation. The overall response rate was 100%. The CMR rates were also high among patients with primary refractory HL, with a rate of 87% any time before consolidation.

A 25% or greater reduction in tumor volume was achieved by 97% of patients, with 94% achieving a 50% or greater reduction. The median duration of response was not yet reached. The 1-year progression-free survival was 91% and the median was not yet reached.

Treatment-related adverse events (TRAEs) of grade 3-4 severity occurred among 18% of patients during induction and 27.3% during intensification. During induction, the most common any grade TRAE were hypersensitivity, nausea, and diarrhea. During intensification, the most common any grade TRAEs were vomiting, nausea, infusion-related reaction, and headache.

“The notable CMR rates after induction with nivolumab plus BV suggest that intensification with BV plus bendamustine could be safety reserved for a subset of patients with an inadequate response to induction therapy, thereby eliminating additional exposure to alkylators for most patients,” the authors concluded in their report.

Disclosures: This study was supported by Bristol Myers Squibb in collaboration with Seagen. Please see the original reference for a full list of disclosures.

Reference
Harker-Murray P, Mauz-Körholz C, Leblanc T, et al. Nivolumab and brentuximab vedotin with or without bendamustine for R/R Hodgkin lymphoma in children, adolescents, and young adults. Blood. 2023;141:2075-2084. doi: 10.1182/blood.2022017118