Randomized Phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma

John P. Leonard, Kathryn S. Kolibaba, James A. Reeves, Anil Tulpule, Ian W. Flinn, Tatjana Kolevska, Robert Robles, Christopher R. Flowers, Robert Collins, Nicholas J. DiBella, Steven W. Papish, Parameswaran Venugopal, Andrew Horodner, Amir Tabatabai, Julio Hajdenberg, Jaehong Park, Rachel Neuwirth, George Mulligan, Kaveri Suryanarayan, Dixie Lee EsseltineSven De Vos

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Abstract

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP (P = .611). Two-year PFS rateswere 77.6%with R-CHOP and 82.0%with VR-CHOP; they were 65.1% versus 72.4%in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade $ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

Original languageEnglish (US)
Pages (from-to)3538-3546
Number of pages9
JournalJournal of Clinical Oncology
Volume35
Issue number31
DOIs
Publication statusPublished - Nov 1 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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