Priority Research Papers:

A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia

Neil E. Kay _, Paolo Strati, Betsy R. LaPlant, Jose F. Leis, Daniel Nikcevich, Timothy G. Call, Adam M. Pettinger, Connie E. Lesnick, Curtis A. Hanson and Tait D. Shanafelt

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Oncotarget. 2016; 7:78269-78280. https://doi.org/10.18632/oncotarget.13412

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Neil E. Kay1, Paolo Strati1, Betsy R. LaPlant1, Jose F. Leis2, Daniel Nikcevich3, Timothy G. Call1, Adam M. Pettinger1, Connie E. Lesnick1, Curtis A. Hanson1 and Tait D. Shanafelt1

1 Mayo Clinic College of Medicine, Rochester, MN, USA

2 Mayo Clinic College of Medicine, Scottsdale, AZ, USA

3 Essentia Health’s East Region, Duluth, MN, USA

Correspondence to:

Neil E. Kay, email:

Keywords: CLL, chemoimmunotherapy, bevacizumab

Received: October 15, 2016 Accepted: November 09, 2016 Published: November 16, 2016


Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF) with in vitro pro-apoptotic and antiangiogenic effects on chronic lymphocytic leukemia (CLL) cells. As monotherapy in patients with CLL, it has no clinical activity. Here we report the results of an open-label, randomized phase II trial comparing the combination of pentostatin, cyclophosphamide and rituximab (PCR) either without or with bevacizumab (PCR-B) in previously untreated CLL patients. A total of 65 evaluable patients were enrolled, 32 receiving PCR and 33 PCR-B. A higher rate of grade 3-4 cardiovascular toxicity was observed with PCR-B (33% vs. 3%, p < 0.003). Patients treated with PCR-B had a trend for a higher complete remission (CR) rate (54.5% vs 31.3%; p = 0.08), longer progression-free survival (PFS)(p = 0.06) and treatment-free survival (TFS)(p = 0.09). No differences in PFS and TFS by IGHV mutational status were observed with the addition of bevacizumab. A significant post-treatment increase in VEGF levels was observed in the PCR-B arm (29.77 to 57.05 pg/mL); in the PCR-B arm, lower baseline CCL-3 levels were significantly associated with achievement of CR (p = 0.01). In conclusion, the addition of bevacizumab to chemoimmunotherapy in CLL is generally well-tolerated and appears to prolong PFS and TFS.

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