Alemtuzumab May Lead to Longer Overall Survival in CLL Patients With Poor Prognostic Factors

Results from three studies presented at the ASH meeting showed that treatment with alemtuzumab (Campath) had activity in high-risk chronic lymphocytic leukemia (CLL) patients who have poor prognostic indicators.

Treatment for CLL can be complicated by genetic risk factors. In some cases of CLL, at least one of the 23 pairs of chromosomes in a cell is found to be either deleted or part of it is lost. One deletion that is occasionally seen in CLL patients is the loss of the short arm of chromosome 17 (17p deletion), which may indicate a poor prognosis including significantly inferior survival compared to other CLL patients. Past studies have shown that treatment-­naive CLL patients were less likely to have 17p deletions than previously treated patients with CLL, indicating that cytogenetic abnormalities may be acquired during the course of treatment. Effective CLL therapies for patients with 17p deletion are limited.

Alemtuzumab Monotherapy
In one analysis of high-risk patients (abstract 3164), authors used the largest database available on the efficacy of alemtuzumab monotherapy to conduct a retrospective analysis of treatment with the drug in 138 patients with advanced CLL, stratified according to cytogenetics. Of these patients, 33% had the 17p deleted cytogenetic abnormality. Alemtuzumab administration was found to provide an overall response rate of 38% in the total cohort, and an overall response rate of 44% in patients with 17p deletion. Additionally, in patients with 17p deletion, treatment with alemtuzumab resulted in progression-free and overall survival durations of 7.1 and 19.1 months, respectively.

“Data show that some people with CLL who have 17p abnormalities may have poor outcomes and may not respond as well to standard chemotherapeutic agents,” said lead investigator Michael Fiegl, md, department of internal medicine, Academic Natters Hospital, Natters, Austria. “This analysis showed activity in patients across all cytogenetic categories-including high-risk patients with 17p deletion and in patients where conventional chemotherapy has failed. The results of this analysis warrant further prospective, clinical studies in patients with 17p deletion.”

Combination Therapy
A second study (abstract 2095) evaluated combination therapy with CFAR (cyclophosphamide, fludarabine, alemtuzumab, and rituximab [Rituxan]) as a front-line therapy in high-risk CLL patients. Of the 48 patients evaluated in this ongoing trial, 28% had 17p deletion. In the total cohort, treatment with the CFAR regimen resulted in an overall response rate of 94% and a complete response rate of 69%. In patients with 17p deletion, treatment with the CFAR regimen resulted in an overall response rate of 77% and a complete response rate of 54%.

“Patients with 17p deletion who have active disease and need treatment are at high risk for lower complete and overall remission rate, shorter progression-free and overall survival,” said lead investigator William G. Wierda, md, phd, assistant professor of medicine, M.D. Anderson Cancer Center, Houston. “In this analysis, Campath in combination with the FCR regimen showed activity in previously untreated patients with 17p deletion. The CFAR regimen may be a viable first-line therapy for patients in this population, although further study is warranted.”

Fludarabine-Refractory Patients
In a third multicenter study (abstract 329) of 103 CLL patients who were fludarabine-refractory, unfavorable genetics were frequent (17p deletion: 29%, 11q deletion: 19%, unmutated IgVH: 68%, TP53 mutation: 34%). In this study, patients received doses of alemtuzumab three times per week. After a median follow-up of 37.9 months, the study found an overall response rate of 34%, a complete response rate of 4%, and a partial response rate of 30% among the total patient population. Median progression-free survival time was 7.7 months, and median overall survival time was 19.1 months.