Interim Report of Phase II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients with Disseminated Stage Diffuse Large B-Cell Lymphoma.

Abstract 2688

Poster Board II-664

Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) and dose-dense CHOP therapy has improved the treatment results of diffuse Large B-cell lymphoma (DLBCL) patients. Nevertheless, a substantial number of patients progress or relapse. Bortezomib is a proteasome inhibitor that is widely used in myeloma treatment and was recently approved for use in mantle cell lymphoma treatment. Its antitumor activity in DLBCL patients was reported in several studies, both as a single agent and in combination with chemotherapy. In this study, we tried to add bortezomib to dose-dense CHOP every 2 weeks to evaluate the complete response (CR) rate and safety of the treatment. Patients with previously untreated disseminated stage DLBCL and age 70 years or less were eligible. All patients received CHOP (Cyclophosphamide 750 mg/m² IV, doxorubicin 50mg/m² IV, vincristine 1.4mg/m² IV on day 1, and prednisolone 100mg PO on days 1 to 5) and granulocyte colony-stimulating factor at a dose of 5μg/kg from days 4 to 13 every 2 weeks. Bortezomib, as recommended by the previous phase I trial, was administered at a dose of 1.6mg/m² on days 1 and 4 of each cycle. Thirty-five patients were enrolled from March, 2007 to March 2009. Total 188 cycles of treatment were done. Twenty-six patients finished planned 6 cycles of treatment, while 9 patients could not continue all planned treatment due to treatment related toxicities and one patient experienced disease progression after 5 cycles of treatment. Twenty-four patients had a CR (92.4%), one patient had a partial response (3.8%), and one patient had a progressive disease (3.8%). Grade 3 hematologic toxicity episodes occurred including 20 anemia (10.7%), 4 neutropenia (2.1%), and 6 thrombocytopenia (3.2%). Grade 4 hematologic toxicity episodes comprised 2 anemia (1.6%), 11 neutropenia (5.9%), and 6 thrombocytopenia (3.2%). One patient died of severe infection with neutropenia. Among 35 patients, grade 3 non-hematologic toxicity occurred with fatigue (11.4%), nausea (2.9%), vomiting (5.7%), diarrhea (8.6%), abdominal pain (8.6%), and sensory neuropathy (20.0%). One patient experienced grade 4 constipation. This interim analysis shows that bortezomib plus dose-dense CHOP every two weeks showed promising activity in disseminated DLBCL patients as the first-line treatment with acceptable toxicity. Further accrual will be continued till the planned patient enrollment goal for phase II results.