A Multicenter Phase II Study of Bendamustine with Rituximab in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

ABSTRACT Background Effective salvage therapies are needed in patients with relapsed/refractory (r/r) DLBCL after R-CHOP. Therapy with bendamustine plus rituximab (B-R) was well tolerated and effective in the preceding phase I study in r/r aggressive B-cell NHL, including DLBCL. This phase II study assessed the efficacy and safety of B-R in patients with r/r DLBCL. Methods Patients with histologically confirmed DLBCL (excluding transformed disease) and 1–3 prior therapies received R 375 mg/m2 IV on day 1 and B 120 mg/m2 IV on days 2 and 3 of each 21-day cycle (cyc), for up to six cycs. Recovery of ANC to ≥1000/mm3 and PLT to 75 000/mm3 were required before the start of each cyc; treatment delays >2 weeks resulted in discontinuation. The primary end point was overall response rate (ORR); secondary end points included complete response (CR) rate, progression-free survival (PFS), and safety. Results A total of 63 patients were enrolled; data from 59 patients were available. Median age was 67 years with 37 patients over 65 years. The majority of patients (64.4%) had one prior therapy; 57 patients (96.6%) were previously treated with R-containing chemotherapy and 8 (13.6%) had prior auto-PBSCT. Patients received a median of 4 (range, 1–6) cycs. Sixteen (27.1%) patients completed 6 cycs; most common reasons for early discontinuation were disease progression (n = 15) and failure to meet criteria to start the next cyc (n = 13). Among 59 patients evaluable for response, ORR was 62.7% with a 37.3% CR rate. The median PFS was 200 days (95% CI, 109–410). Most common grade 3/4 adverse events (AEs) included CD4 decreased (66.1%), neutropenia (54.2%) and thrombocytopenia (10.2%). Four (6.8%) patients discontinued due to serious AEs. Conclusions B-R demonstrated promising activity in patients with r/r DLBCL. Toxicity was primarily hematologic and generally manageable. These results suggest that B-R is a promising salvage regimen for patients with r/r DLBCL after R-CHOP.