Barbara Eichhorst, MD, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, Cologne, Germany, described the confirmation of the superiority of a frontline chemotherapy with a regimen involving fludarabine plus cyclophosphamide plus rituximab (FCR) compared with bendamustine plus rituximab (BR) in previously untreated, physically fit patients with advanced chronic lymphocyte leukemia (CLL).

The study was prompted by results from the researchers’ previous demonstration of significantly better overall survival in CLL patients treated with FCR compared with BR. Presently, 564 physically fit patients with untreated and active CLL, and no deletions in chromosome 17p were randomized to receive FCR intravenously (n = 284; fludarabine 25 mg/m², days 1–3; cyclophosphamide 250 mg/m², days 1–3; and rituximab 375 mg/m², day 0 in cycle 1 and 500 mg/m², day 1 during cycles 2-6) or BR intravenously (n = 280; bendamustine 90 mg/m², days 1–2; rituximab 375 mg/m², day 0 in cycle 1 and 500 mg/m², day 1 during cycles 2-6).

The study arms were comparable at baseline with the exceptions of a greater proportion of patients aged > 65 years (30.5% vs 38.7%; P = .042), greater mean number of cycles (5.27 vs 5.41; P = .022), and prevalence of immunoglobulin heavy chain variable (IGHV) mutations (55.3% vs 67.8%; P = .003) for the BR arm.

The intention-to-treat population received FCR (n = 282) and BR (n = 279). The primary end point of progression-free survival (PFS) in the intention-to-treat population during the follow-up observation time was reached, with a hazard ration of 1.6 that was statistically significant.

During a median observation time of 37.1 months (range, 0-59.9 months), complete response was observed in 39.7% and 30.8% of patients in the FCR and BR arms, respectively (P = .034). The overall response rate was comparable in the FCR and BR arms (95.4% and 95.7%, respectively; P = 1.0). Those treated with FCR achieved higher rates of minimal residual disease at all time points (Table 1).

The FCR regimen produced significantly better PFS in patients treated with unmutated IGHV than the BR regimen (42.7 vs 33.6 months; P = .017), but not in patients with mutated IGHV (not reached vs 52.0 months; P = .153). The FCR regimen was significantly more beneficial than the BR regimen in terms of PFS in patients aged ≤ 65 years (53.6 vs 38.5 months; P < .001) but not in older patients (not reached vs 48.5 months; P = .170). Overall survival was similar (FCR, 90.6%; BR, 92.2%; P = .897).

Neutropenia was more frequent in the FCR arm (84.2% vs 59.0%; P < .001), as was thrombocytopenia (21.5% vs 14.4%; P = .03), all infections (39.1% vs 26.8%; P < .001), and infections during the first 5 months after therapy (11.8% vs 3.6%; P < .001). Those aged > 65 years treated with FCR were significantly more likely to experience infection (47.7% vs 20.6%; P < .001).

The data demonstrate the inferiority of BR vs FCR with respect to PFS and complete response rate and the association of FCR with higher rates of neutropenia and severe infection. The researchers concluded that FCR remains as the standard therapy in fit patients, with BR considered as alternative treatment in fit, but elderly, patients.