Fludarabine, cyclophosphamide, and rituximab (FCR) was associated with improved progression-free survival compared with bendamustine plus rituximab in fit patients with chronic lymphocytic leukemia (CLL), but the latter regimen was associated with less toxic effects, a study published in The Lancet Oncology has shown.1
Although chemoimmunotherapy with FCR is the standard treatment modality for physically fit patients with advanced CLL, it is associated with various toxicities. Therefore, researchers sought to compare the efficacy and tolerability of standard FCR vs bendamustine plus rituximab, a potentially less toxic combination.
For the phase 3 study, researchers enrolled 564 treatment-naïve fit patients with CLL aged 33 to 81 years without del(17p). Participants were randomly assigned to receive 6 cycles of fludarabine 25 mg/m2/day IV and cyclophosphamide 250 mg/m2/day IV for the first 3 days or to bendamustine 90 mg/m2/day for the first 2 days of each cycle. Patients in both arms received rituximab 375 mg/m2 IV on day 0 of cycle 1 and subsequently at a dose of 500 mg/m2 on day 1 during the next 5 cycles.
Results showed that after a median follow-up of 37.1 months, median progression-free survival was 41.7 months (95% CI, 34.9-45.3) with bendamustine plus rituximab compared with 55.2 months (95% CI not evaluable) with FCR (HR, 1.643; 90.4% CI, 1.308-2.064).
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In regard to safety, patients in the FCR group were more likely to experience severe neutropenia and infections than those in the bendamustine-rituximab group. Patients who were older than 65 years had an increased frequency of infectious complications with FCR.
The findings ultimately suggest that FCR should remain the standard- frontline therapy in treatment-naïve fit patients with advanced CLL despite bendamustine plus rituximab being associated with fewer toxicities.
- Eichhorst B, Fink A-M, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial [published online ahead of print May 20, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)30051-1.