Fludarabine-Cyclophosphamide-Rituximab Treatment in Chronic Lymphocytic Leukemia, Focusing on Long Term Cytopenias Before and After the Era of Targeted Therapies

Abstract

The widespread application of fludarabine, cyclophosphamide, and rituximab combination is limited due to its toxicity, particularly the prolonged cytopenias. The study aimed to compare the prolonged cytopenias depending on fitness and report real-life data on dose reduction measures and efficacy. According to our database, 120 and 14 patients were treated with FCR between 2011 and 2015 and between 2016 and 2019. Out of the first cohort, 34 patients were treated in subsequent lines. The complete and partial remission rate after first-line treatment was 79%, 16% in the first cohort and 86%, 14% in the second cohort, respectively; and 47%, 35% after non first-line treatment. Based on today’s standards, only 37.5% of the patients were fit for FCR. The frequency of persistent cytopenia was 14%, and it was significantly associated with fitness (χ2 (1) = 6.001, p = 0.014 for all patients). The small number of FCR treated patients after 2016 shows how the availability of targeted therapies, mostly ibrutinib, in later lines changed the first-line choice. Recently, it is recommended first-line for fit patients with mutated IGHV and no TP53 aberrations. With this narrow indication, a decrease in the frequency of persistent cytopenias is predicted.