Chemoimmunotherapy With Fludarabine, Cyclophosphamide, and Rituximab for Relapsed and Refractory Chronic Lymphocytic Leukemia

TLDR

The study evaluated the efficacy, toxicity, and tolerability of fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in 177 previously treated chronic lymphocytic leukemia patients, aiming to improve complete remission rates and bone marrow response quality. Patients received rituximab 375 mg/m² on day 1 of cycle 1 and 500 mg/m² thereafter, fludarabine 25 mg/m²/day on days 2–4 of cycle 1 and 1–3 of cycles 2–6, and cyclophosphamide 250 mg/m²/day on days 2–4 of cycle 1 and 1–3 of cycles 2–6, with six 4‑week courses administered. The regimen yielded a 25 % complete remission rate, a 73 % overall response rate, 32 % of CRs achieved molecular remission, and myelosuppression was the most common toxicity, representing the highest CR rate reported for previously treated CLL.

Abstract

The efficacy, toxicity, and tolerability of chemoimmunotherapy with the combination of fludarabine, cyclophosphamide, and rituximab (FCR) were evaluated in previously treated patients with chronic lymphocytic leukemia (CLL). The purpose of this study was to improve the complete remission (CR) rate for previously treated patients and evaluate the quality of bone marrow response.One hundred seventy-seven previously treated patients with CLL were evaluated. Treatment consisted of rituximab 375 mg/m(2) day 1 of course 1 and 500 mg/m(2) day 1 of courses 2 to 6; fludarabine 25 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6; and cyclophosphamide 250 mg/m(2)/d days 2 to 4 of course 1 and days 1 to 3 of courses 2 to 6. Courses were repeated every 4 weeks.CR was achieved in 25% of 177 patients, and nodular partial remission and partial remission were achieved in 16% and 32% of patients, respectively; the overall response rate was 73%. Twelve (32%) of 37 complete responders tested achieved molecular remission in bone marrow. Univariate and multivariate analyses were used to identify pretreatment patient characteristics associated with CR and overall remission, longer time to progression, and overall survival.The FCR regimen was an active and well-tolerated treatment for previously treated patients with CLL. Myelosuppression was the most common toxicity. FCR induced the highest CR rate reported in a clinical trial of previously treated patients with CLL. Furthermore, molecular remissions were achieved in a third of patients achieving CR.