Fludarabine, Cyclophosphamide, Rituximab Remain Standard of Care in Very Fit Patients with Leukemia

SAN FRANCISCO—Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) remains standard of care in very fit patients with advanced chronic lymphocytic leukemia (CLL), yielding higher complete response rates and minimal residual disease negativity and longer progression-free survival (PFS) compared with bendamustine and rituximab (BR), final analysis of the German CLL Study Group CLL10 study (Abstract 19) presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition has shown.

However, in patients who were fit and elderly, high rates of toxicity and infection led to dose reductions and similar efficacy between the two arms, suggesting this population or those with previous infections might benefit from BR as an alternative regimen, said Barbara Eichhorst, MD, of the Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University Hospital in Cologne, Germany.

The phase 3 study CLL10 study evaluated the efficacy and tolerance of the two regimens in fit patients without del(17p). Research was conducted at 158 sites in Germany, Austria, Switzerland, Denmark, and the Czech Republic. A total of 564 patients were randomly assigned 1:1 to receive 6 courses of FCR (n=284; fludarabine 25 mg/m² IV d1-3, cyclophosphamide 250 mg/m² IV d1-3, rituximab 375 mg/m² IV d0 at first cycle and 500 mg/m² d1 all subsequent cycles; q 28 days) or BR (n=280; bendamustine 90 mg/m² IV d1+2, rituximab 375 mg/m² IV d0 at first cycle and 500 mg/m² d1 all subsequent cycles; q 28 days).

At a median observation time of 37.1 months, overall response rate was 95.4% in the FCR arm and 95.7% in the BR arm (P=1.0). Complete response was 39.7% with FCR compared with 30.8% with BR (P=0.034)

Median PFS was 55.2 months in patients receiving FCR and 41.7 months in patients receiving BR (hazard ratio=1.626; P<0.001)..

The BR regimen was associated with lower rates of neotropenias and severe infections in patients who were elderly, Dr. Eichhorst concluded.

Reference

1. Eichhorst, Barbara, MD. “19 Frontline Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Shows Superior Efficacy in Comparison to  Bendamustine (B) and Rituximab (BR) in Previously Untreated and Physically Fit Patients (pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Final Analysis of an International, Randomized Study of the German CLL Study Group (GCLLSG) (CLL10 Study).” ASH 2014. Oral Presentation. December 6, 2014.