Safety and efficacy of Combination of Fludarabine, Cyclophosphamide, and Rituximab compared to Chemotherapy alone in Chronic Lymphocytic Leukemia Patients

Background: Chronic lymphocytic leukemia, one of the most common hematological malignancies, has been treated with several treatment regimens. Recently chemoimmunotherapy with Fludarabine, Cyclophosphamide, and Rituximab (FCR) regimen have shown significant success in treating these patients. Aim: This systematic review aims compare the efficacy and safety of chemoimmunotherapy combination (FCR) to chemotherapy alone (FC) in chronic lymphocytic leukemia patients. Methods: Three healthcare related databases were systematically searched: PubMed, Cochrane registry for clinical trials, and cumulative index for nursing and allied health literature (CINAHL) with appropriate combination of keywords and medical subject headings (MeSH). Then, duplicate citations were removed from the search result followed by Title/Abstract screening. After that, these are articles underwent full text screening based on the inclusion and exclusion criteria. Data were extracted regarding overall survival (OS), progression free survival (PFS), objective response rate (ORR), and serious adverse effects. For risk of bias analysis JADAD score was utilized. Results: Total number six clinical trials were involved with total 3433 patients, 1723 patients in the experimental arm and 1710 patients in the control arm. Five out of six clinical trials reported higher progression free survival (PFS) in the experimental arm, four out of five clinical trials reported higher overall survival (OS) in the experimental arm, and four out of five clinical trials reported higher objective response rate (ORR) in the experimental arm. Majority of the clinical trials of good quality with JADAD score 3 or more for five clinical trials. Conclusion: Chemoimmunotherapy with FCR is more effective than chemotherapy alone with FC regimen, however, toxicity is higher in the experimental arm. Future trials should focus on adverse effects