Bortezomib (Velcade) for progressive myeloma after autologous stem cell transplantation and thalidomide

Abstract

Twenty-one patients with multiple myeloma, all relapsed after frontline autologous stem cell transplantation and all relapsed again after or resistant to thalidomide (employed as second line treatment) received bortezomib (1.3 mg/m 2 body surface twice weekly for 2 weeks followed by an interval of 10-12 days) without adjunct of steroids as third line therapy. Three patients died of progressive disease during the first 2 cycles with bortezomib. Eighteen patients received at least 2 cycles and were evaluated for response. According to EBMT criteria, two complete (negative immunofixation) and seven partial (reduction of M-component > 50-75%) remissions were achieved (ITT response rate 42.8%). Duration of response lasted from 2 to 14+ months. Grades 3-4 toxicities (thrombocytopenia, leucopenia, peripheral neuropathy and vasculitis) were observed in seven patients, but no patient interrupted the treatment due to side effects. We conclude that bortezomib alone may induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide.

Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post‐allogeneic transplantation for high‐risk myeloma patients

“…Accordingly, new strategies are required to reduce both the risk of relapse and the toxicity of the procedure. Bz has been studied in the context of relapse after autologous SCT, showing a response rate of 35% to 43% (Richardson et al , ; Musto et al , ). Also a phase II study showed that Bz and dexamethasone followed by donor lymphocyte infusion is safe, resulting in an ORR of 68% (20% CR) (Montefusco et al , ).…”

Bortezomib Inhibits Cell-Cell Adhesion and Cell Migration and Enhances Epidermal Growth Factor Receptor Inhibitor–Induced Cell Death in Squamous Cell Cancer

“…Currently, it is approved for the treatment of multiple myeloma (25,32,33). Bortezomib's mechanism of antitumor activity, however, is still poorly understood.…”

“…Bortezomib is a selective inhibitor of the 26S proteasome and has been approved for the treatment of multiple myeloma (25). Preclinical and early clinical data suggest that bortezomib also has significant antitumor activity in other types of cancer, including squamous cell cancer (SCC) of the head and neck (HNSCC; ref.…”

Recent Advances in Anti-Angiogenic Therapy of Cancer

“…It was also found to induce high quality responses as third line salvage therapy with acceptable toxicity in a significant proportion of homogeneously pre-treated myeloma patients with progressive disease after autologous transplantation and thalidomide. [119]. In a Phase 3 trial involving 669 myeloma patients treated with at least one prior therapy, bortezomib increased median, improved overall survival, and increased response rate, compared with high-dose dexamethasone [120].…”