Study Suggests Patient Age Should Factor Into CLL Treatment Selection

Jennifer Woyach, MD

Patients with chronic lymphocytic leukemia (CLL) will benefit from different therapies based on their age, according to new research from the Ohio State University Comprehensive Cancer Center (OSUCCC). The findings suggest that chlorambucil may be better than fludarabine in treating older patients with CLL, and that rituximab therapy is beneficial regardless of age.

For this study, first author Jennifer Woyach, MD, assistant professor of Hematology at the OSUCCC Arthur G. James Cancer Hospital (OSUCCC-James), and colleagues evaluated 663 patients enrolled in four successive Cancer and Leukemia Group B trials in an effort to determine the best frontline therapy for older patients with CLL.

In patients >69 years of age, limited outcome analysis of treatment with the current standard chemoimmunotherapy used in younger patients—fludarabine plus rituximab or fludarabine, cyclophosphamide, and rituximab—has indicated lower response rates and greater toxicity.

Woyach et al examined overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in patients <70 years of age and those ≥70 for five treatment regimens: chlorambucil; fludarabine; fludarabine with consolidation alemtuzumab; fludarabine plus rituximab; and fludarabine plus rituximab with consolidation alemtuzumab.

Although a significant difference in ORR was found among the treatment regimens, age was not a factor in the variance. The lowest ORR was seen in the chlorambucil group (37%; 95% CI, 0.30-0.44). Patients treated with fludarabine had an improved ORR (60%; 95% CI, 0.53-0.68), and ORR was even better with the fludarabine-plus-rituximab combination (84%; 95% CI, 0.75-0.90).

The investigators did note age group differences in PFS and OS among the regimens. Patients aged <70 years being treated with fludarabine had a 40% reduced risk of progression compared with patients receiving chlorambucil (HR = 0.60; 95% CI, 0.46-0.78); however, for patients in the older group, risk of progression did not differ for the two therapies (HR = 1.04; 95% CI, 0.65-1.65). With OS, fludarabine decreased the risk of death by 31% versus chlorambucil in patients aged <70 years (HR = 0.69; 95% CI, 0.53-0.90). In contrast, the risk of death with fludarabine versus chlorambucil was 45% higher for patients aged ≥70 years, although this finding did not reach statistical significance (HR = 1.45; 95% CI, 0.92-2.28).

Adding rituximab to fludarabine improved PFS (HR = 0.56) and OS (HR = .65) among all patients, regardless of age. Also independent of age, adding alemtuzumab did not significantly improve ORR, PFS, or OS versus regimens administered without alemtuzumab consolidation.

“Our findings apply to both routine care of CLL patients 70 years and older and to future CLL trials,” principal investigator John Byrd, MD, professor of Medicine, Medicinal Chemistry, and Veterinary Biosciences at the OSUCCC-James, said in a statement. “The study suggests that chlorambucil is superior to fludarabine in older patients, and that CD20 antibody therapies such as rituximab are beneficial as front-line therapy for all CLL patients, regardless of age.”

The study authors wrote that their findings point toward a need for future studies with a specific focus on older CLL patients, noting that the combination of chlorambucil and rituximab “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.”

Woyach JA, Ruppert AS, Rai K, et al. Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential Cancer and Leukemia Group B studies [published online ahead of print December 10, 2012]. J Clin Oncol. doi: 10.1200/JCO.2011.41.5646.