Addition of granulocyte macrophage colony stimulating factor does not improve response to early treatment of high-risk chronic lymphocytic leukemia with alemtuzumab and rituximab

Leuk Lymphoma. 2013 Mar;54(3):476-82. doi: 10.3109/10428194.2012.717276. Epub 2012 Aug 22.

Abstract

Thirty-three previously untreated patients with high-risk chronic lymphocytic leukemia (CLL) were treated before meeting standard criteria with alemtuzumab and rituximab. Granulocyte macrophage colony stimulating factor (GM-CSF) was added to the regimen to determine whether it would improve treatment efficacy without increasing toxicity. High risk was defined as at least one of the following: 17p13-; 11q22.3-; unmutated IGHV (or use of VH3-21) together with elevated expression of ZAP-70 and/or CD38. Treatment was subcutaneous GM-CSF 250 μg Monday-Wednesday-Friday for 6 weeks from day 1, subcutaneous alemtuzumab 3 mg-10 mg-30 mg from day 3 and then 30 mg Monday-Wednesday-Friday for 4 weeks, and intravenous rituximab (375 mg/m(2)/week) for 4 weeks from day 8. Patients received standard supportive care and were monitored weekly for cytomegalovirus (CMV) reactivation. Using standard criteria, 31 (94%) patients responded to treatment, with nine (27%) complete responses (one with persistent cytopenia) and nine (27%) nodular partial responses. Median progression-free survival was 13.0 months and time to next treatment was 33.5 months. No patient died during treatment, seven (21%) had grade 3-4 toxicities attributable to treatment, and 10 (30%) had CMV viremia. Addition of GM-CSF to therapy with alemtuzumab and rituximab decreased treatment efficacy and increased the rate of CMV reactivation compared to a historical control.

Trial registration: ClinicalTrials.gov NCT00562328.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cytomegalovirus / physiology
  • Cytomegalovirus Infections / diagnosis
  • Cytomegalovirus Infections / virology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Remission Induction
  • Risk Factors
  • Rituximab
  • Time Factors
  • Treatment Outcome
  • Virus Activation

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Monoclonal, Murine-Derived
  • Alemtuzumab
  • Rituximab
  • Granulocyte-Macrophage Colony-Stimulating Factor

Associated data

  • ClinicalTrials.gov/NCT00562328