Abstract
BACKGROUND.
Patients with chronic lymphocytic leukemia (CLL) usually are treated only for progressive disease. However, the discovery of biologic predictors of a high risk of disease progression, together with the development of newer, more targeted therapies, could change this paradigm. In this phase 2 study, the authors tested the safety and efficacy of early treatment for patients with highโrisk CLL using alemtuzumab and rituximab.
METHODS.
Patients were eligible for treatment if they were 1) previously untreated, 2) had no National Cancer InstituteโWorking Group 1996 criteria for treatment, and 3) had at least 1 marker of highโrisk disease 17p13โ, 11q22โ, or a combination of unmutated IgVH and CD38+/ZAP70+). Treatment consisted of subcutaneous alemtuzumab (initial dose escalation followed by 30 mg on Monday, Wednesday, and Friday for 4 weeks) and intravenous rituximab (375 mg/m^2^ per week ร4 doses). All patients received Pneumocystis pneumonia and herpes virus prophylaxis and were monitored for cytomegalovirus reactivation.
RESULTS.
Twentyโseven of 30 patients (90%) responded to therapy with 11 (37%) complete responses (CRs). Five patients (17%) patients who had a CR had no detectable minimal residual disease. The median response duration was 14.4 months, and only 9 patients required retreatment for progressive disease at the time of the current report (median followโup, 17.6 months). Study patients had a significantly longer time from diagnosis to first treatment for CLL according to conventional indications than a comparison cohort with similar biologic risk profiles.
CONCLUSIONS.
The therapy regimen used was safe and effective for early treatment of patients with highโrisk CLL. Further studies will be required to determine whether this early treatment strategy decreases morbidity and mortality for highโrisk CLL. Cancer 2008. ยฉ 2008 American Cancer Society.