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Addition of Bortezomib to R-CHOP in DLBCL Subtypes Identified With Gene-Expression Profiling

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Key Points

  • The addition of bortezomib did not significantly improve progression-free survival in the combined germinal center B-cell and activated B-cell populations.
  • The addition of bortezomib did not improve progression-free survival in either of the subgroups.

In the phase III REMoDL-B trial reported in The Lancet Oncology, Davies et al found that the addition of bortezomib to standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) did not improve progression-free survival subtypes of diffuse large B-cell lymphoma (DLBCL) identified with gene-expression profiling.

Prior studies suggested that the addition of bortezomib to chemoimmunotherapy improved progression-free survival in patients with the activated B-cell subtype vs those with the germinal center B-cell subtype.

Study Details

In the open-label multicenter trial, 918 previously untreated patients enrolled between June 2011 and June 2015 were treated with one 21-day cycle of standard R-CHOP. During this initial treatment, gene-expression profiling using routine diagnostic biopsy samples was performed to determine the cell-of-origin subtype of each patient (ie, germinal center B-cell, activated B-cell, or unclassified). Patients were then randomly assigned, with stratification for international prognostic index score and cell-of-origin subtype, to continue R-CHOP alone for 5 additional cycles (n = 459) or to receive bortezomib plus R-CHOP for 5 cycles (RB-CHOP; n = 459). Overall, 244 patients (26.6%) had activated B-cell disease, 475 (51.7%) had germinal center B-cell disease, and 199 (21.7%) had unclassified disease.

The primary endpoint was 30-month progression-free survival in the combined germinal center B-cell and activated B-cell populations.

Progression-Free Survival

Median follow-up was 29.7 months. Progression-free survival at 30 months in the combined germinal center and activated B-cell population was 74.3% in the RB-CHOP group vs 70.1% in the R-CHOP group (hazard ratio [HR] = 0.86, P = .28). The addition of bortezomib did not significantly improve progression-free survival in the activated B-cell subgroup (adjusted HR = 0.78, P = .27), the germinal center B-cell subgroup (adjusted HR = 0.85, P = .35), or the unclassifiable subgroup (adjusted HR = 1.29, P = .34).

Adverse Events

The most common grade ≥ 3 adverse events were hematologic events, occurring in 42.1% of the RB-CHOP group vs 39.8% of the R-CHOP group. Neuropathy of any grade occurred in 56.8% vs 41.6% of patients, but grade ≥ 3 neuropathy was observed in only 3.8% vs 1.8% of patients. Serious adverse events occurred in 50.2% vs 42.5% of patients, including 4 vs 5 treatment-related deaths.

The investigators concluded, “This is the first large-scale study in diffuse large B-cell lymphoma to use real-time molecular characterization for prospective stratification, randomization, and subsequent analysis of biologically distinct subgroups of patients. The addition of bortezomib did not improve progression-free survival.”

Peter W.M. Johnson, FMedSci, of the Cancer Research UK Centre, University of Southampton, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Janssen-Cilag, Bloodwise, and Cancer Research UK. The study authors’ full disclosures can be found at thelancet.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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