Addition of Bortezomib to R-CHOP in Non–Germinal Center B-Cell–Like Lymphoma
A phase II trial reported in the Journal of Clinical Oncology by Leonard et al showed no significant progression-free survival benefit of adding bortezomib (Velcade) to R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) in previously untreated patients with non–germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL).
Study Details
In the trial, 206 patients from 69 U.S. sites were randomized between October 2009 and July 2013 to receive six 21-day cycles of standard R-CHOP (n = 103) or R-CHOP plus bortezomib at 1.3 mg/m2 on days 1 and 4. The primary endpoint was progression-free survival among the 183 patients (92 in bortezomib group and 91 in the control group) with centrally confirmed non-GCB DLBCL who received at least 1 dose of study drug.
Progression-Free Survival
After a median follow-up of 34 months, progression-free survival events had occurred in 18% of the bortezomib group vs 25% of the control group. Median progression-free survival was not reached in either group. Progression-free survival at 2 years was 82.0% vs 77.6% among all evaluable patients (hazard ratio [HR] = 0.73, P = .611), 72.4% vs 65.1% among patients with high-intermediate/high International Prognostic Index (IPI) scores (HR = 0.67, P = .606), and 88.9% vs 90.0% among those with low/low-intermediate IPI scores (HR = 0.85, P = .958).
Overall response rates were 96% vs 98%. Median overall survival was not reached in either group (HR = 0.75, P = .763). Survival at 2 years was 93.0% vs 88.4% among all patients, 92.1% vs 79.2% among those with high-intermediate/high IPI scores (HR = 0.62, P = .638), and 93.8% vs 97.7% among those with low/low-intermediate scores (HR = 1.02, P = .999).
Toxicity
Grade ≥ 3 adverse events in the bortezomib vs control group included neutropenia in 49% vs 53%, thrombocytopenia in 29% vs 13%, anemia in 15% vs 7%, leukopenia in 25% vs 26%, and neuropathy in 5% vs 1%. Serious adverse events occurred in 34% vs 31%. Treatment was discontinued due to adverse events in 6% vs 4%.
The investigators concluded: “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.”
The study was supported by Millennium Pharmaceuticals.
John P. Leonard, MD, of Meyer Cancer Center, Weill Cornell Medicine and NewYork-Presbyterian Hospital, is the corresponding author of the Journal of Clinical Oncology article.
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®.
