Activated B-cell (ABC) and molecular high-grade (MHG) subgroups, as identified by gene expression profiling (GEP), appeared to benefit from the addition of bortezomib to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) among patients with diffuse large B-cell lymphoma (DLBCL) treated in the phase 3 REMoDL-B trial (ClinicalTrials.gov Identifier: NCT01324596).
In the primary analysis of the REMoDL-B study, the addition of bortezomib to R-CHOP failed to improve progression-free survival (PFS) or overall survival (OS) in the combined cohort. A 5-year update and a retrospective molecular subgroup analysis were reported in the Journal of Clinical Oncology.
REMoDL-B was a phase 3 adaptive trial that randomly assigned 1077 patients with previously untreated DLBCL to receive R-CHOP with or without bortezomib. Patients were stratified by molecular subtype and 801 were successfully classified by GEP.
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At baseline, the median age was 64 and 44% of patients were female. The majority of patients had an Eastern Cooperative Oncology Group performance status of 0 or 1. The International Prognostic Index score was low among 27% of patients, low-intermediate among 25%, high-intermediate among 29%, and high among 17%. The molecular phenotype was ABC among 30% of patients, germinal center B-cell among 59%, and MHG among 10%.
For the entire cohort, the addition of bortezomib did not improve PFS (hazard ratio [HR], 0.81; P =.085) or OS (HR, 0.86; P =.32) at a median follow-up of 64 months.
However, bortezomib improved PFS and OS among patients with ABC or MHG DLBCL. The 5-year PFS was 69.4% with bortezomib plus R-CHOP compared with 54.4% with R-CHOP alone (HR, 0.65; 95% CI, 0.43-0.98; P =.041). The 5-year OS was 80.4% and 67.4% with bortezomib and R-CHOP or R-CHOP alone, respectively (HR, 0.58; 95% CI, 0.35-0.95; P =.032).
In the MHG subgroup, the 5-year PFS was 55% with bortezomib plus R-CHOP compared with 29% with R-CHOP alone (HR, 0.46; 95% CI, 0.26-0.84; P =.011). However, OS was similar between treatment groups in the ABC subgroup, with a rate of 60.0% in the bortezomib group at 5 years compared with 47.5% in the R-CHOP alone group (HR, 0.62; 95% CI, 0.32-1.20; P =.016).
There were no new safety signals in the updated analysis. There were a total of 20 secondary cancers reported of 1041 patients in the safety analysis. Of these, 1.4% were in the bortezomib group and 2.3% were in the R-CHOP group.
“This study confirms that different molecular subtypes of DLBCL exhibit different responses to bortezomib when given in combination with R-CHOP,” the authors concluded in their report. “With mature follow-up, this study suggests a benefit from the addition of bortezomib to R-CHOP for ABC and MHG subtypes of DLBCL.”
Disclosures: This study was supported in part by Janssen-Cilag. Please see the original reference for a full list of disclosures.
Reference
Davies AJ, Barrans S, Stanton L, et al. Differential efficacy from the addition of bortezomib to R-CHOP in diffuse large B-cell lymphoma according to the molecular subgroup in the REMoDL-B study with a 5-year follow-up. J Clin Oncol. Published online March 27, 2023. doi: 10.1200/JCO.23.00033
