FCR for Advanced Chronic Lymphocytic Leukemia: Real Life Results from a Series of 50 Patients Treated at a Single Institution
Authors: Gravetti Angela , Monaco Giuseppe , Copia Carolina , Palmieri Salvatore , Ronconi Fioravante , Rocco Stefano , Ferrara Felicetto 
Published: October 2019

Abstract
Introduction: The combination of fludarabine, cyclophoshamide and rituximab (FCR) represents the current standard of treatment of fit patients with chronic lymphocytic leukemia (CLL). However, despite the success of the FCR regimen, a number of questions exist on its optimal administration as well as on its short and long term toxicity. As a consequence, in the daily practice (Knauf et al, Hematological Oncology, 2015) less intensive regimens such as bendamustine plus rituximab (BR) are often adopted also in fit patients. Most data on the FCR regimen derive from clinical trials, while data from real life are poor.
Methods: Here we report our experience on a series of 50 previously untreated patients with CLL, managed with FCR at a single institution in Italy. Patients were programmed to receive 6 courses plus 2 additional rituximab infusions. The median age of the whole patient population was 60 years (range 41-75), there were 29 males (58%) and 21 females (42%). 44 patients (88 %) received the classical schedule (Fludarabine 25 mg/sqm and Cyclophosphamide 250 mg/sqm, on days 1-3) , while 6 patients (12%), all aged over 70 years, were given FCR-lite (Fludarabine 15 mg/sqm and Cyclophosphamide 200 mg/sqm). In all patients Rituximab was given at 375 mg/sqm on course 1, and 500 mg/sqm infusions 2 to 6. According to Binet staging system, 20 patients were in stage B and 30 in stage C. Patients were carefully selected according to the absence of hepatic, cardiac, renal and respiratory comorbidity and medical judgment (go patients). 40 patients were evaluable for cytogenetic examination (FISH) and none of them had 17 p abnormality.
Results: Overall, 46 patients (92%) received the 6 programmed FCR courses, while in four patients therapy was stopped after 1, 2, 4 and 5 courses due to unexplained cytopenia, while CLL cells were undetectable in the bone marrow. Overall response rate was 90 % (74 % CR, 16 % PR) The median duration of response was 30 months, after a median follow up of 38 months. 8 patients have relapsed from CR achievement and 2 of them achieved sustained response with BR, one is on treatment with ibrutinib, while 5 were refractory to salvage therapy. 5 patients died in the setting of refractory disease, 44 are alive and one has been lost to follow-up. Major toxicities (grade 3-4) included: neutropenia registered in 25 patients (50 %), needing G-CSF administration in all cases and producing delay in the administration in 35 % of patients; anemia requiring blood transfusions was registered in 10% of the cases, while no patient required platelet units. Hepatitis B and Herpes Zoster virus reactivation occurred in 1 (2%) and 2 patients (4%), respectively. Overall, 5 patients were hospitalized, all because of febrile neutropenia successfully managed with antibiotic therapy and G-CSF.
Conclusions: We conclude that FCR in the "real life" is effective and well tolerated in patients with advanced CLL, provided that a careful evaluation of is made as to eligibility to therapy, mainly in terms of absence of comorbidities.
This work was supported by AIL Napoli, "Sezione Bruno Rotoli".

Disclosures
No relevant conflicts of interest to declare.