FCR and bevacizumab treatment in patients with relapsed chronic lymphocytic leukemia

Abstract

Background: Patients with relapsed chronic lymphocytic leukemia (CLL) often achieve response with chemoimmunotherapy but have short remission durations. Studies have shown that patients with CLL have increased angiogenesis in the microenvironment; levels of proangiogenic growth factors such as VEGF and/or angiopoietin-2 are also elevated. Increased angiogenesis correlates with poor outcome in CLL. Bevacizumab (B) is a humanized monoclonal antibody targeting VEGF-A.

Methods: In this study, we analyzed whether a combination of bevacizumab with fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy (FCR-B) could improve outcomes in patients with relapsed CLL. Sixty-two patients were enrolled. The median age of the patients was 60 years (range, 31-84 years) and 40% had received >1 prior therapy for CLL. Sixty-one patients were evaluable for toxicity, and 57 were evaluable for response. Six cycles were planned; 36 patients (59%) completed ≥4-6 cycles of the regimen.

Results: The overall response rate was 79%, with 13 (23%) complete remissions (CRs), 8 nodular partial remissions (14%), and 24 partial remissions (43%). The median progression-free survival and overall survival rates were 13.5 and 45 months, respectively. Grade 3 or 4 toxicities included febrile neutropenia (n = 40), infections (n = 21), thrombocytopenia (n = 18) and anemia (n = 9).

Conclusions: Results with FCR-B were similar to those observed with an historical cohort of relapsed patients treated with FCR.

Keywords: FCR; anti-angiogenic therapy; bevacizumab; chemoimmunotherapy; chronic lymphocytic leukemia, CLL.

Conflict of interest statement

Conflicts of Interests - The authors report no competing conflicts of interest.

© 2014 American Cancer Society.

Figures

Figure 1. Progression free survival (PFS) by therapy in patients receiving FCR-B and FCR

Shows comparison of FCR-B with the historical cohort of patients who were treated with salvage FCR (P=0.05).

Figure 2

Progression free survival (PFS) by different FISH (Fluorescent in-situ hybridization) cytogenetic categories (del17p, del11q, negative FISH, trisomy 12 and del13q) in patients receiving FCR-B (P=0.037).

Figure 3. Overall survival (OS) by therapy in patients receiving FCR-B and FCR

Shows comparison of FCR-B with the historical cohort of patients who were treated with salvage FCR (P=0.48).

Figure 4

Overall survival (OS) by different FISH (Fluorescent in-situ hybridization) cytogenetic categories (del17p, del11q, negative FISH, trisomy 12 and del13q) in patients receiving FCR-B (P=0.0015).