Supported by the French LYSA (Lymphome Du Manteau 2010 SA) group, this prospective phase 2 trial evaluated the efficacy and safety of a 4-drug combination known as RiBVD (rituximab, bendamustine, bortezomib, and dexamethasone) in elderly patients with previously untreated mantle- cell lymphoma (MCL), including patients older than 65 years or patients who were not eligible for autologous stem-cell transplantation.
Qualifying patients received a total of 6 cycles of the RiBVD regimen if they responded after 4 cycles. The regimen was administered every 4 weeks. Primary prophylaxis with acyclovir was mandatory for herpes virus reactivation; no antibiotics were recommended for bacterial prophylaxis. Gressin and colleagues presented preliminary analysis of the RiBVD regimen after 4 cycles of treatment.
Of the 76 patients enrolled, 70 patients were evaluated. The patients’ median age was 72 years. Most patients were male with advanced stage MCL and a good performance status. In addition, the MIPI (Mantle-Cell Lymphoma International Prognostic Index) scores indicated mostly intermediate- and high-risk disease.
Among the 70 evaluable patients, the overall response rate was 87%, including 60% of patients who achieved complete response (CR) or CR unconfirmed. Of the 61 patients who received a PET (positron emission tomography) scan after 4 cycles, 64% achieved CR. Overall, 3 patients experienced disease progression.
The adverse events (AEs) associated with RiBVD included grade 3 or 4 neutropenia (21%), grade 3 or 4 thrombocytopenia (15%), and grade 3 or 4 anemia (2%). Nonhematologic AEs reported in more than 10% of cycles included fatigue; allergic reactions; fever without neutropenia; neuropathy; weight loss; cutaneous rash; gastrointestinal symptoms; and elevated transaminase levels, creatinine levels, and glucose levels. Serious AEs included 4 deaths: 1 patient died of pneumonia, 2 patients died of cardiac arrest, and 1 patient died of progressive multifocal leukoencephalopathy. Other serious AEs included 12 infections (ie, pneumonia, herpes zoster, listeriosis). In addition, 4 incidences of febrile neutropenia and 3 incidences of cutaneous hypersensitivity reactions were reported.
Overall, the safety profile of RiBVD appears acceptable and manageable. This interim analysis demonstrates the efficacy of 4 cycles of RiBVD in patients with untreated MCL. The high overall response rate has been shown to be predictive of a long duration of response.
Gressin R, Callanan M, Daguindau N, et al. The RiBVD regimen (rituximab IV, bendamustine IV, velcade SC, dexamethasone IV) offers a high complete response rate in elderly patients with untreated mantle cell lymphoma. Preliminary results of the LYSA trial “Lymphome Du Manteau 2010 SA”. Blood. 2013;122. Abstract 370.