Bendamustine combined with rituximab for patients with relapsed or refractory diffuse large B cell lymphoma

Abstract

Patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) are treated with salvage regimens and may be considered for high-dose chemotherapy and autologous stem cell transplantation if disease is chemosensitive. Bendamustine is active in indolent B cell lymphomas and chronic lymphocytic leukemia but has not been extensively studied in aggressive lymphomas. This trial examines the combination of bendamustine and rituximab in patients with relapsed and refractory DLBCL. Patients received bendamustine at 90 mg/m2 (n = 2) or 120 mg/m2 (n = 57) on days 1 and 2 and rituximab at 375 mg/m2 on day 1 every 28 days for up to 6 cycles. The study evaluated objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and treatment safety. Fifty-nine patients were treated, and 48 were evaluable for response. Median age was 74; 89 % had stage III or IV disease, and 63 % had high revised International Prognostic Index scores; the median number of prior therapies was 1. Based on analysis using the intent-to-treat population, the ORR was 45.8 % (complete response, 15.3 %; partial response, 30.5 %). The median DOR was 17.3 months, and the median PFS was 3.6 months. Grade 3 or 4 hematological toxicities included neutropenia (36 %), leukopenia (29 %), thrombocytopenia (22 %), and anemia (12 %). The combination of bendamustine and rituximab showed modest activity in patients with relapsed and refractory DLBCL and has an acceptable toxicity profile.

Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression

“…One limitation of that study, similar to limitations in our study, is that responses were not analyzed by cell of origin. 32 Assessing responses to brentuximab vedotin by cell of origin of DLBCL would be an interesting exploratory analysis, although CD30 expression does not clearly correspond to the GCB or the ABC subtype of DLBCL. [15][16][17][18] Other limitations of this study are the lack of a comparator arm, absence of central review of response, and lack of analysis of response by other potentially important prognostic markers, such as Bcl-2 or c-Myc.…”

Follicular dendritic cell sarcoma treated with a variety of chemotherapy

“…In addition, clinical trials evaluating the use of bendamustine in diffuse large B‐cell lymphoma, an intermediate grade lymphoma, are under way. The result of a phase II clinical trial to evaluate the effectiveness of bendamustine in previously treated diffuse large B‐cell lymphoma reported that the overall response rate was 62.7%, the complete response rate was 37.3%, and the progression‐free survival was 6.7 months 17. Bendamustine is expected to become a key drug for the treatment of intermediate grade lymphoma.…”

R-ICE Chemotherapy with or without Autologous Transplantation for Elderly Patients with Relapsed or Refractory Aggressive B-Cell Lymphomas

“…Previously-reported treatments for elderly patients with relapsed aggressive B-cell lymphomas ineligible for autologous transplantation included the rituximab-gemcitabine-oxaliplatin protocol with a 5-year PFS and OS rate of 14% [10], the rituximab-bendamustine protocol, which resulted in a median PFS time of 4 months in 1 study [11] and of 8 months in another [12], and the R-DHAP protocol, which was associated with a median OS of 28 months in a study that also included other entities [13]. With the R-ICE protocol, the 3-year PFS and OS rates were 32 and 35%, respectively, and the median PFS and OS times were 9 and 12 months, respectively.…”