Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: Final analysis of an open-label phase II study.

Abstract

PURPOSE:

Most patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL.

PATIENTS AND METHODS:

Patients with first-line CLL were treated with rituximab (375 mg/m(2) on day 1, cycle one, and 500 mg/m(2) thereafter) plus chlorambucil (10 mg/m(2)/d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety.

RESULTS:

A total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (range, 43 to 86 years), with patients having a median of seven comorbidities. Hematologic toxicities accounted for most grade 3/4 adverse events reported, with neutropenia and lymphopenia both occurring in 41% of patients and leukopenia in 23%. Overall response rates were 84%, with CR achieved in 10% of patients. Median progression-free survival was 23.5 months; median overall survival was not reached.

CONCLUSION:

These results compare favorably with previously published results for chlorambucil monotherapy, suggesting that the addition of rituximab to chlorambucil may improve efficacy with no unexpected adverse events. R-chlorambucil may improve outcome for patients who are ineligible for fludarabine-based treatments.

• Authors: Peter Hillmen, John G Gribben, George A Follows, Donald Milligan, Hazem A Sayala, Paul Moreton, David G Oscier, Claire E Dearden, Daniel B Kennedy, Andrew R Pettitt, Amit Nathwani, Abraham Varghese, Dena Cohen, Andy Rawstron, Stephan Oertel, Christopher F E Pocock
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 12 Pg. 1236-41 (Apr 20 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 24638012 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Chlorambucil
• Rituximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Chlorambucil (administration & dosage, adverse effects)
• Comorbidity
• Female
• Humans
• Leukemia, Lymphocytic, Chronic, B-Cell (drug therapy)
• Male
• Middle Aged
• Rituximab
• Treatment Outcome