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.

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 rates were 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.

• Authors: 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 Esseltine, Sven de Vos
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 35 Issue 31 Pg. 3538-3546 (Nov 01 2017) ISSN: 1527-7755 [Electronic] United States
• PMID: 28862883 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• R-CHOP protocol
• Rituximab
• Vincristine
• Bortezomib
• Doxorubicin
• Cyclophosphamide
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bortezomib (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Disease-Free Survival
• Doxorubicin (administration & dosage, adverse effects)
• Female
• Humans
• Lymphoma, Large B-Cell, Diffuse (diagnostic imaging, drug therapy, pathology)
• Male
• Middle Aged
• Prednisone (administration & dosage, adverse effects)
• Rituximab
• Vincristine (administration & dosage, adverse effects)
• Young Adult