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).
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.
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).
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.
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