Follicular lymphoma (FL) is an incurable B-cell non-Hodgkin's lymphoma (NHL) representing around 20% of all NHL. Rituximab (R) is approved for the treatment of CD20+ relapsed/refractory FL, and single-agent bortezomib has shown activity in heavily pretreated patients. Bortezomib and R (VR) show additive activity in preclinical models, and the combination was active and well tolerated in a Phase 2 study.
The results from a randomised, open-label, multicentre, international, Phase 3 clinical trial, which compared the efficacy and safety of VR versus R alone in patients with relapsed or refractory, R-naive or R-sensitive FL, were presented at ASH 2010.1 Statistically significant improvements in PFS, response rate and time to next anti-lymphoma treatment were observed. This was associated with acceptable additional toxicity. Median PFS significantly improved from 334 days with R alone to 389 days with VR.
The overall response rate was 63% with VR versus 49% with R (p<0.001), including 25% and 18% verified complete response rates, respectively (p=0.035). The durable response rate (>6 months) was 50% with VR versus 38% with R (p=0.002). The median time to subsequent anti-lymphoma treatment was significantly improved in the VR versus R arm (700 vs 537 days, p=0.027). Median overall survival was not reached in either group.
The final results from a prospective, randomised, sequential, international, multicentre, 2-arm, non-comparative, open-label, clinical study of two bortezomib schedules in patients with recurrent or refractory FL were also presented at ASH.2
The first treatment arm (A) received 1.5 mg/m2 bortezomib administered biweekly on days 1, 4, 8 and 11 of a 21-day cycle for 8 cycles. The second treatment arm (B) received 1.6 mg/m2 bortezomib administered weekly on days 1, 8, 15 and 22 of a 35-day cycle for 6 cycles. Treatment allocation was stratified according to number of prior therapies (1 or 2 versus > 2) and time to progression for the last given anti-lymphoma therapy (≤ 12 months versus > 12 months). 32% in arm A and 23% in arm B achieved a complete, unconfirmed complete or partial response at the end of treatment. Median duration of response was 16 and 15 months and PFS was 6 and 7.5 months, respectively. The investigators concluded that the 1.5 mg/m2 bortezomib dose schedule should be recommended for further clinical study.
A Phase II multicentre study has been conducted to evaluate the safety and efficacy of VR in relapsed/refractory indolent non-follicular lymphoma (linfocytic lymphoma [LL] or marginal zone lymphoma [MZL]) and mantle cell lymphoma (MCL) not eligible for high-dose chemotherapy.3
The results indicated that this combination is effective and safe in the treatment of these patients. Overall clinical response rate was 53% and overall response rate by histology was 37% in LL, 50% in MZL and 64% in MCL. This was unaffected by rituximab pre-treatment, but was response rates were higher in relapsed patients compared with refractory patients (64% and 38%). With a median follow-up of 25 months, 2-year overall survival was 80% and 2-year PFS was 25%.
1. B Coiffier, E Osmanov, X Hong et al A Phase 3 Trial Comparing Bortezomib Plus Rituximab with Rituximab Alone In Patients with Relapsed, Rituximab-Naive or -Sensitive, Follicular Lymphoma Abstract 857 presented at 52nd ASH, Orlando, FL, December 4-7, 2010
2. V Ribrag, H Tilly, O Casasnovas et al Final Results of a Randomized Phase 2 Multicenter Study of Two Bortezomib Schedules In Patients with Recurrent or Refractory Follicular Lymphoma Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study FL-05. Abstract 768 presented at 52nd ASH, Orlando, FL, December 4-7, 2010.
3. A Chiappella, P Pregno, PL Zinzani et al Weekly Infusion of Bortezomib In Combination with Rituximab In Relapsed/Refractory Indolent Non-Follicular and Mantle Cell Lymphoma Is Safe and Effective: Two-Years Analysis of Phase II Trial BRIL06 of Intergruppo Italiano Linfomi (IIL) Abstract 3965 presented at 52nd ASH, Orlando, FL, December 4-7, 2010.
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