Bortezomib Plus Rituximab in Patients with Indolent Non-Hodgkin’s Lymphoma (NHL): A Phase 2 Study.

Background: Bortezomib (VELCADE^®, Vc) a novel, first-in-class proteasome inhibitor, is being investigated in the treatment (tx) of non-Hodgkin’s lymphoma (NHL). Preclinical data with combined rituximab (R) and Vc suggest additive cytotoxic activity. This phase 2 study investigated the response rate to R plus Vc, weekly or twice-weekly, in patients (pts) with relapsed follicular (FL) or marginal zone (MZL) NHL.

Methods: Eligibility criteria included CD20+ FL or MZL with measurable disease, and Karnofsky Performance Status (KPS) ≥50% (ECOG 0–2). Pts on any prior regimen including R had to respond and show TTP of ≥4 months. Pts were randomized (1:1) to Vc 1.3mg/m² twice-weekly on days 1, 4, 8, and 11 of a 21-day cycle (Arm A) or Vc 1.6mg/m² weekly on days 1, 8, 15, and 22 of a 35-day cycle (Arm B) for up to 15 weeks (5 and 3 cycles in arms A and B, respectively). Starting from day 1, R 375mg/m² was administered weekly for 4 weeks. Response was evaluated by International Workshop Criteria.

Results: 81 pts were enrolled between May 2004 and August 2005. At data reporting for this abstract, 46 (23 each arm) had received study drug, and 42 (20 Arm A, 22 Arm B) were evaluable for response. Of these 42 pts, 83% had FL and 17% had MZL; 62% were male; 55% were aged >60 years (range 33–80); 93% had KPS ≥90%; 26% had lactic dehydrogenase level >ULN. 71% of pts received prior R (alone or in combination), and 79% of pts received prior CHOP, RCHOP, CVP or RCVP. Of 46 treated pts, 9 (39%) in Arm A and 16 (70%) in Arm B completed all planned cycles. Median Vc dose received was 15.9mg/m² (61% of max. expected) in Arm A, and 19.0mg/m² (99% of max. expected) in Arm B. Overall response rate was 50% (1 CR + 9 PR) in Arm A, and 45% (2 CR + 8 PR) in Arm B. 12 pts had PD (6 each arm) and 1 pt died (Arm A). Time to event analyses, including TTP and duration of response, are pending further follow-up. Tx was well tolerated in both arms; grade ≥3 AEs were seen in 10 pts in Arm A and 5 pts in Arm B. The most common grade ≥3 AEs were gastrointestinal toxicities, neutropenia, thrombocytopenia and peripheral neuropathy, but no grade ≥3 thrombocytopenia or neutropenia were observed in Arm B. SAEs were seen in 7 pts in Arm A versus 2 pts in Arm B.

Conclusions: Weekly and twice weekly Vc plus R are active and well tolerated treatments for relapsed/refractory CD20+ indolent NHL. The more convenient weekly regimen appears to offer a similar response rate with less toxicity. Final efficacy and safety data for both regimens will be presented.