Chlorambucil Effective for CLL in Elderly
Will Boggs, M.D.
Chlorambucil is safe and effective for chronic lymphocytic leukemia (CLL) in older patients, according to data from sequential Cancer and Leukemia Group B (CALGB) studies.
Limited enrollment of older patients in pivotal trials of chemoimmunotherapy for CLL leaves open the question of what the best treatment is for these patients. Standard therapy for younger patients includes fludarabine and rituximab or fludarabine, cyclophosphamide, and rituximab, but two studies have suggested that chlorambucil plus rituximab is safe and effective in older CLL patients.
Dr. John C. Byrd from Ohio State University in Columbus and colleagues used data from four CALGB studies to examine the effects of chlorambucil, fludarabine, fludarabine plus rituximab, fludarabine with alemtuzumab consolidation, and fludarabine/rituximab with alemtuzumab consolidation on outcomes in patients aged 70 years and older.
In multivariable models, the estimated risk of progression did not differ significantly between chlorambucil and fludarabine for older patients. This was in contrast to the 40% decrease in the risk of progression when younger patients were treated with fludarabine.
Adding rituximab to fludarabine cut the risk of progression by 44% relative to fludarabine alone, and this effect was consistent across age groups. Adding alemtuzumab, however, did not improve progression-free survival over similar regimens without alemtuzumab, the researchers reported online December 10th in the Journal of Clinical Oncology.
Overall survival for patients 70 and older did not vary significantly across the treatment regimens.
The risk of death among older patients was estimated to be 45% higher with fludarabine than with chlorambucil, but this difference fell short of statistical significance.
As with progression-free survival, overall survival improved with the addition of rituximab to fludarabine, regardless of age, and there was little overall survival benefit with the addition of alemtuzumab consolidation.
"Chlorambucil is a reasonable chemotherapeutic backbone on which to design new combination regimens in this age group," the researchers conclude. "With recent data regarding the combination of chlorambucil and rituximab in older patients, this combination is certainly a standard therapeutic option for older patients and may be an ideal platform on which to add new targeted agents to improve efficacy."
Dr. Barbara F. Eichhorst from Uniklinik Koln, Koln, Germany was lead author of the report of the German CLL5 study but was not involved in this new analysis. She told Reuters Health in an email, "Chlorambucil is better than fludarabine in elderly patients. Fludarabine plus rituximab was better in comparison to fludarabine alone in both age groups. Because chemoimmunotherapies might be too toxic in elderly patients with comorbidity burden, results from studies for patients with higher comorbidity will show if less toxic chemoimmunotherapies are the new standard in this patients group as well."
"In Germany," she continued, "we favor (chlorambucil monotherapy) for patients with a high comorbidity burden, defined as a cumulative illness rating scale score >6. But based on the data of two phase II studies chlorambucil plus rituximab would be another option. We expect as new standard therapy in 2013 chlorambucil plus anti-CD20 antibody."
Chlorambucil Effective for Chronic Lymphocytic Leukemia in Elderly. Medscape. Dec 13, 2012.
J Clin Oncol 2012.
Gregory D. Pawelski