title: A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia.
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.
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Paolo
authors.initials: P
authors.lastname: Strati
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Betsy R
authors.initials: BR
authors.lastname: LaPlant
authors.affiliation: Mayo Clinic College of Medicine, Scottsdale, AZ, USA.
authors.forename: Jose F
authors.initials: JF
authors.lastname: Leis
authors.affiliation: Essentia Health's East Region, Duluth, MN, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nikcevich
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Call
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Pettinger
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Connie E
authors.initials: CE
authors.lastname: Lesnick
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Curtis A
authors.initials: CA
authors.lastname: Hanson
authors.affiliation: Mayo Clinic College of Medicine, Rochester, MN, USA.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D016207:Cytokines / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D006801:Humans; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015649:Pentostatin / Q000008:administration & dosage; D012074:Remission Induction; D000069283:Rituximab / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D000074322:Antineoplastic Agents, Immunological; D016207:Cytokines; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D015649:Pentostatin; D000069283:Rituximab; D003520:Cyclophosphamide
keywords: CLL; bevacizumab; chemoimmunotherapy