ORLANDO, Fla.Bendamustine (BEN) should be considered a “backbone” drug in first-line chemotherapy of patients with advanced chronic lymphocytic leukemia (CLL) due to its significantly greater efficacy compared with chlorambucil (CLB) with no compromise to quality of life (QoL) in this older and potentially comorbid population, follow-up data from the registration trial has found.

In 2008, BEN received US Food and Drug Administration approval for the treatment of CLL based on the results of a prospective, randomized, open-label phase 3 trial (Knauf et al., J Clin Oncol. 2009;27:4378-84) comparing BEN with CLB in patients with previously untreated advanced (Binet stage B/C) CLL. Patients were randomized to either BEN 100 mg/m2 on days 1 and 2 (n=162) or CLB 0.8 mg/kg on days 1 and 15 (n=157) for up to 6 treatment cycles.

The primary end points were overall response rate (complete response plus partial response) and progression-free survival. Overall survival and QoL were secondary end points; QoL was analyzed using EORTC questionnaires QLQ C30 and QLQ-CLL25. The investigators also examined time to next treatment and efficacy of second-line regimens.

This follow-up study in 319 patients found BEN offered significantly greater response rates as well as prolonged progression-free survival, and resulted in a much longer time to treatment compared with CLB. Overall survival was significantly prolonged in all survivors, especially those who achieved a complete response after treatment with BEN, Wolfgang Ulrich Knauf, MD, Krankenhaus Bethanien Department of Hematology/Oncology, Frankfurt, Germany, and colleagues reported during the 52nd American Society of Hematology Annual Meeting and Exposition.

Median age of the patients was 64 years (range, 35 to 75 years). In both study arms, mean number of treatment cycles was 6. Median observation time was 54 months. Overall response rate was 68% with BEN vs 31% with CLB (P<0.0001). In the BEN arm, 31% of patients had a complete response vs 2% of patients with CLB (P<0.0001). In the intent-to-treat population, median progression-free survival was 21.2 months in the BEN arm vs 8.8 months with CLB (P<0.0001).

As of this analysis, 59 patients in the BEN-treated group and 34 in the CLB-treated group had not received any second-line treatment (P<0.004). Median time to next treatment in the intent-to-treat population was 31.7 months with BEN group and 10.1 months with CLB (P<0.001). After second-line therapy of any type, overall response rate was 36.9% in patients who had received BEN first-line and 48% for those who had received CLB first-line (P=0.106).

As of October 2010, no difference has been observed in overall survival among the intent-to-treat population (P=0.257). However, those patients who did achieve a complete response—almost exclusively after treatment with BEN—experienced a longer overall survival that those who did not (median not reached vs 75.9 months; P=0.0018). In addition, patients who achieved any response (complete response plus partial response) after either BEN or CLB had a longer overall survival than nonresponders (median not reached vs 68.3 months; P<0.001).

Among the 319 patients evaluable for QoL analysis (162 in the BEN group and 157 in the CLB group), there was no difference between groups in baseline scores for QoL parameters and no difference after completion of study treatment (ie, a mean of 6 cycles administered), in physical, social, emotional, or cognitive function. Self-assessment of global health status also revealed no difference, the investigators concluded.

BEN is also approved for the treatment of indolent B-cell non-Hodgkin’s lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab–containing regimen.