Coiffier B et al. Proc ASH 2010;Abstract 857.

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Presentation transcript:

Coiffier B et al. Proc ASH 2010;Abstract 857. A Phase III Trial Comparing Bortezomib plus Rituximab with Rituximab Alone in Patients with Relapsed, Rituximab-Naïve or -Sensitive, Follicular Lymphoma Coiffier B et al. Proc ASH 2010;Abstract 857.

Bortezomib1 + Rituximab2 (Vc-R) n = 336 Study Schema Bortezomib1 + Rituximab2 (Vc-R) n = 336 Eligibility Relapsed or progressed FL Rituximab naïve or sensitive Grade 1 or 2 FL with >1 measurable lesion R Rituximab2 (R only) n = 340 1 Bortezomib 1.6 mg/m2 d1, 8, 15, 22 q5wk x 5 cycles 2 Rituximab 375 mg/m2 d1, 8, 15, 22 in cycle 1 and d1 only in cycles 2-5 Coiffier B et al. Proc ASH 2010;Abstract 857.

Efficacy Endpoints Overall Response 63% 49% 0.569 <0.001 Vc-R (n = 315) R Only (n = 324) Odds Ratio p-value Overall Response 63% 49% 0.569 <0.001 Durable Response (>6 months) 50% 38% 0.608 0.002 Complete Response 25% 18% 0.665 0.035 Vc-R (n = 336) R Only (n = 340) Hazard Ratio Progression-Free Survival (PFS) 12.8 mo 11.0 mo 0.822 0.039 Time to next treatment 23.0 mo 17.7 mo 0.802 0.027 Coiffier B et al. Proc ASH 2010;Abstract 857.

Progression-Free Survival in High-Risk Follicular Lymphoma Vc-R R Only Hazard Ratio p-value Median PFS (FLIPI ≥ 3) (n = 139; 140) 11.4 months 7.9 months 0.707 0.0133 Median PFS (High Tumor Burden by GELF) (n = 185; 179) 11.3 months 8.4 months 0.751 0.0186 Coiffier B et al. Proc ASH 2010;Abstract 857.

Select Adverse Events Diarrhea All Grades Grade >3 52% 7% 8% 0% Vc-R (n = 334) R Only (n = 339) Diarrhea All Grades Grade >3 52% 7% 8% 0% Neutropenia 17% 11% 4% Peripheral Sensory Neuropathy 16% 3% 1% Febrile Neutropenia (Grade >3) Coiffier B et al. Proc ASH 2010;Abstract 857.

Conclusions Addition of weekly bortezomib to rituximab therapy in patients with relapsed FL is associated with statistically significant improvements in: - PFS (primary endpoint) - Response rate - Time to next antilymphoma treatment Patients at high risk in the bortezomib–rituximab arm had significantly longer PFS than patients treated with rituximab alone. Increase in side effects did not affect feasibility of treatment or quality of life (data not shown). Coiffier B et al. Proc ASH 2010;Abstract 857.

Sacchi S et al. Proc ASH 2010;Abstract 1801. Phase II Study of Bortezomib plus Rituximab in Relapsed Follicular Lymphomas Sacchi S et al. Proc ASH 2010;Abstract 1801.

Study Schema Eligibility (N = 37) Relapsed FL CD20+ Bortezomib1 + Rituximab2 1 Bortezomib 1.3 mg/m2 d1, 4, 8, 11 q21d x 6 cycles 2 Rituximab 375 mg/m2 d1 in cycles 3-6, and q21d x 2 additional doses Sacchi S et al. Proc ASH 2010;Abstract 1801.

Efficacy and Safety Results Response Evaluable (n = 33) Overall Response Complete Response Partial Response 58% 49% 9% Safety Evaluable (n = 33) Neuropathy Neutropenia Infections Grade 1-2 Grade 3-4 30% 15% 6% 3% Sacchi S et al. Proc ASH 2010;Abstract 1801.

Conclusions Bortezomib and rituximab combination in relapsed follicular lymphoma has a promising percentage of responses. Longer follow-up is needed to evaluate response duration and survival. Toxicity with the combination of bortezomib and rituximab in relapsed FL is acceptable. Sacchi S et al. Proc ASH 2010;Abstract 1801.

Investigator Commentary: Bortezomib with Rituximab for Relapsed FL Coiffier and colleagues demonstrated a higher overall response rate, complete response rate and time to disease progression with the combination arm in a large number of patients. Unfortunately, it was a negative study, because they did not meet their goal of a 33 percent improvement in progression-free survival. It remains to be seen whether this regimen will be adopted by practicing clinicians, because it is associated with considerably more toxicity, particularly peripheral neuropathy. The study reported by Sacchi evaluated the same regimen of bortezomib/rituximab, but it was not a randomized trial and it included a smaller number of patients. Approximately 50 percent of the patients achieved a complete response, with an overall response rate of 58 percent. Other regimens, such as bendamustine/rituximab, for this patient population are associated with a considerably higher response rate and might be considered a preferable therapy. Interview with Bruce D Cheson, MD, December 23, 2010