Bendamustine in Monotherapy and in Combination Regimens in the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma – a Retrospective Analysis

In this study, we carried out a retrospective analysis of the efficacy and toxicity of bendamustine in patients with B-cell lymphoproliferative diseases.

Bendamustine was administered both in monotherapy and combined protocols in 111 patients, including 81 patients with chronic lymphocytic leukaemia (CLL), 20 patients with indolent lymphoma, and 10 patients with aggressive lymphoma (8 mantle cell lymphoma and 2 diffuse large B-cell lymphoma). Median age of patients was 61 years (range: 44 – 87 years). Almost all patients, except 3 previously untreated patients with CLL had relapsed (78 patients) or refractory disease (30 patients). 60.4% of patients were treated with bendamustine plus rituximab, while 28.2% received bendamustine in monotherapy, and 31.4% received other combined regimens.

Overall response rate (ORR) was 65.8%, including 20.7% of complete response (CR) and 45.1% of partial response (PR). In CLL patients, ORR was 59.3% with 16% of CR and 43.2% of PR. In patients with indolent NHL, ORR was 80%, including 30% of CR and 50% of PR. In patients with aggressive lymphoma, OR and CR rates were respectively: 90% and 40%. In patients with CLL, a likelihood of response was significantly lower in patients with ZAP-70 expression (p=0.006) and 17p deletion (p=0.009). Median overall survival (OS) for all patients was 11.5 months (range 1–40). For CLL patients, median OS was 11 months (range 1–40), for patients with indolent lymphoma 15.5 months (range 5–29 ) and for patients with aggressive lymphoma - 10 months (6–38). Median OS was significantly longer in patients responding to therapy as compared to non-responders (15 months vs. 8 months; p=0.0001). Median progression-free survival (PFS) in all patients was 6 months (0–38), including 4 months (0–38) for CLL patients, and 8.5 months (0–33) for patients with both aggressive and indolent lymphoma. Among pre-treatment parameters, β₂-microglobulin (RR=1.234; p=0.002), haemoglobin level (RR=0.803; p=0.03) and PLT count (RR=1.005; p=0.03) significantly influenced survival. Also, the higher number of bendamustine cycles was associated with longer overall survival (RR=0.715; p=0.003). In patients with CLL, 17p deletion was associated with reduced overall survival (p=0.021; log-rank test). OS was significantly longer in patients who received ≤ 2 lines of previous therapies as compared to > 3 lines (p=0.018; log-rank test), and who received ≥ 4 courses of therapy (p=0.02; log-rank test). In patients with NHL, both OS and PFS were significantly longer in patients with lactate dehydrogenase level <250 U/l (p= 0.01; p=0.02; respectively), and who received ≥ 4 cycles of treatment (P= 0.03). Toxicity was predominantly haematological, including grade III/IV neutropenia in 32%, thrombocytopenia in 15% and anaemia in 16% of patients.

Bendamustine, both in monotherapy and combination regimens, is an effective therapy with a favourable toxicity profile even in heavily pretreated patients.

Hus:Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Glaxosmithkline: Consultancy. Off Label Use: In Europe bendamustine is indicated for first-line treatment of chronic lymphocytic leukaemia (Binet stage B or C) in patients for whom fludarabine combination chemotherapy is not appropriate and indolent non-Hodgkin's lymphomas as monotherapy in patients who have progressed during or within 6 months following treatment with rituximab or a rituximab containing regimen. Wiktor-Jedrzejczak:Genzyme: Speakers Bureau; Celgene: Speakers Bureau; Genopharm: Speakers Bureau; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy; Janssen-Cilag: Consultancy; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Walewski:Roche: Honoraria, Speakers Bureau; GSK: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees; Cephalon: Research Funding; Mundipharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Dmoszynska:Millenium Pharmaceuticals: Consultancy; Celgene: Consultancy; Mundipharma: Consultancy, Membership on an entity's Board of Directors or advisory committees.