A phase II study of bortezomib and gemcitabine in relapsed mantle cell lymphoma from the National Cancer Institute of Canada Clinical Trials Group (IND 172)

Abstract

Bortezomib and gemcitabine have each shown activity as single agents in mantle cell lymphoma (MCL), which is incurable. The purpose of this phase II study was to determine the efficacy and safety of the previously unstudied combination of bortezomib and gemcitabine in patients with relapsed or refractory MCL. Patients were eligible if they had relapsed MCL with 1-3 prior therapies. Patients were treated with gemcitabine 1000 mg/m(2) on days 1 and 8 and bortezomib 1.0 mg/m(2) IV on days 1, 4, 8, and 11, on a 21-day schedule. Twenty-six patients were evaluable for toxicity and 25 for response. The overall response rate was 60% and the median progression free survival was 11.4 months. The main adverse effects were hematological, with 40% and 48% of patients experiencing grade 3/4 thrombocytopenia and granulocytopenia, respectively. Bortezomib and gemcitabine is an active combination in relapsed and refractory MCL with clinically meaningful results. It offers a chemotherapy backbone to which other agents, less myelosuppressive, may be added.

Lifting the mantle: Unveiling new treatment approaches in relapsed or refractory mantle cell lymphoma

“…Bortezomib has been FDA-approved for the treatment of relapsed/ refractory MCL at a dose of 1.3 mg/m 2 on days 1, 4, 8, and 11 in a 3-week cycle. Bortezomib has also been combined with other agents to heighten efficacy, such as gemcitabine as well as bendamustine and rituximab (the BVR regimen), the latter associated with 71% ORR in relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma [41,42].…”

Bortezomib in Multiple Myeloma: Systematic Review and Clinical Considerations

“…The Hematology dsg has already recommended bortezomib monotherapy for patients with mm refractory to or relapsing within 1 year of the conclusion of initial or subsequent treatments and who are candidates for further therapy 94 . That recommendation was made based on the benefit in os and ttp observed in the apex trial 23 .…”

Hepatitis E Virus Replication Requires an Active Ubiquitin-Proteasome System

“…UPS has been implicated in the infection cycle and virus-host interplay of several viruses (3,9,28,36,51). Bortezomib is an FDA-approved proteasome inhibitor that has demonstrated clinical efficacy in the treatment of multiple myeloma (7,10,27). Therefore, in this study we examined the role of UPS in the replication of hepatitis E virus (HEV) and evaluated the potential use of UPS inhibitors as therapeutic agents against HEV infection.…”