, findings from the phase-2 PYRAMID trial showed.
When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.
There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).
Dr. John P. Leonard
“A potential reason for the lack of benefit with VR-CHOP was that only two doses of bortezomib were given per 21-day cycle, whereas the standard schedule for bortezomib in multiple myeloma is four doses per cycle on days 1, 4, 8, and 11,” wrote John P. Leonard, MD, of Weill Cornell Medicine and New York Presbyterian Hospital, New York, and his colleagues. “In this study, treatment duration was limited to six 21-day cycles of R-CHOP.”
The authors noted that previous research has demonstrated the feasibility of using VR-CHOP and similar immunochemotherapy regimens in DLBCL. In the current PYRAMID (Personalized Lymphoma Therapy: Randomized Study of Proteasome Inhibition in Non-GCB DLBCL) phase 2 trial, VR-CHOP was compared with R-CHOP in 206 patients with previously untreated non-GCB DLBCL who were selected by real-time subtyping conducted or confirmed at a central laboratory that used the Hans algorithm.
The cohort was randomized to receive six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4, and the primary endpoint was PFS.
The hazard ratio (HR) for PFS was 0.73 (90% confidence interval, 0.43-1.24) and favored VR-CHOP (P = .611), while the median PFS was not reached in either group. At 2 years, PFS was 77.6% with R-CHOP, versus 82.0% with VR-CHOP.
Among patients with high-intermediate/high International Prognostic Index (IPI) risk, those rates were 65.1% with R-CHOP, versus 72.4% with VR-CHOP (HR, 0.67; 90% CI, 0.34-1.29; P = .606). For those patients at low/low-intermediate IPI risk, the rates were 90.0% for R-CHOP, versus 88.9% for VR-CHOP (HR, 0.85; 90% CI, 0.35-2.10; P = .958).
The overall response rate was 98% for R-CHOP patients and 96% for VR-CHOP, with complete response rates of 49% and 56%, respectively.
Time to progression rates at 2 years were 79.8% for R-CHOP, versus 83.0% with VR-CHOP (HR, 0.79; 90% CI, 0.45-1.37; P = .767). While median overall survival was not reached in either arm, the HR for the entire cohort was 0.75 (90% CI, 0.38-1.45; P = .763). Two-year overall survival was 88.4% and 93.0%, respectively.
In the high-intermediate/high IPI score group, 2-year overall survival was 79.2% with R-CHOP, versus 92.1% with VR-CHOP (HR, 0.62; 90% CI, 0.25-1.42; P = .638), and for those with low/low-intermediate IPI risk scores, 97.7% versus 93.8% (HR, 1.02; 90% CI, 0.34-3.27; P = .999).
Millennium Pharmaceuticals supported the study. Dr. Leonard and several of the coauthors reported relationships with industry.