Comparison of Different Schedules of Rituximab and Chlorambucil in Previously Untreated Chronic Lymphocytic Leukemia: A Retrospective Study of Krohem

Abstract

Due to age and comorbidities many patients with CLL receive chlorambucil as front-line treatment. Doses and schedules of this drug vary widely but it is not clear whether this affects outcomes. We performed this retrospective analysis to compare the efficacy and toxicity of continuous high-dose chlorambucil (12-20 mg daily until response or toxicity) (cHD-Clb-R) and intermittent high dose chlorambucil (8-10 mg/m2 daily for 7 days q 4 wk) (iClb-R) in combination with rituximab (375 mg/m2/cycle for 8 cycles) in previously untreated CLL patients. Thirtysix patients received cHD-Clb-R and 32 iClb-R. Median age was 66 years (range 41-80); 24 were women and 44 men; 24 had Binet stage A, 27 B and 17 C; 5 had del(17p). Most common severe adverse events were granulocytopenia, occurring in 14; and infections in 7 patients, one of whom died. One patient stopped treatment due to hepatotoxicity. Both schedules resulted in similar toxicity and efficacy (cHD-Clb-R vs. iClb-R overall survival, progression-free survival and survival without next treatment at 30 mo. 70% vs. 83%, 49% vs. 55% and 67% vs. 75% respectively). Combinations of rituximab and chlorambucil are well tolerated and effective treatments for patients ineligible for fludarabine-based regimens. Outcomes seem to be related more to total drug doses than schedules.