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, Tait D. Shanafelt

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)78269-78280
Number of pages12
JournalOncotarget
Volume7
Issue number48
DOIs
StatePublished - 2016

Keywords

  • Bevacizumab
  • CLL
  • Chemoimmunotherapy

ASJC Scopus subject areas

  • Oncology

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    Kay, N. E., Strati, P., LaPlant, B. R., Leis, J. F., Nikcevich, D., Call, T. G., Pettinger, A. M., Lesnick, C. E., Hanson, C. A., & Shanafelt, T. D. (2016). A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia. Oncotarget, 7(48), 78269-78280. https://doi.org/10.18632/oncotarget.13412