Early treatment of high‐risk chronic lymphocytic leukemia with alemtuzumab and rituximab

• Published in: Cancer 2008-10, Vol.113 (8), p.2110-2118
• Main Authors: Zent, Clive S., Call, Timothy G., Shanafelt, Tait D., Tschumper, Renee C., Jelinek, Diane F., Bowen, Deborah A., Secreto, Charla R., LaPlant, Betsy R., Kabat, Brian F., Kay, Neil E.
• Format: Article
• Language: English
• Subjects: Aged; Alemtuzumab; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm - administration & dosage; Antibodies, Neoplasm - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biological and medical sciences; Bone Marrow - pathology; chronic lymphocytic leukemia; Disease Progression; early stage; Female; Flow Cytometry; Hematologic and hematopoietic diseases; high risk; Humans; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemia, Lymphocytic, Chronic, B-Cell - genetics; Leukemia, Lymphocytic, Chronic, B-Cell - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Risk; Rituximab; Time; Tumors
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.23824

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 high‐risk CLL using alemtuzumab and rituximab. METHODS. Patients were eligible for treatment if they were 1) previously untreated, 2) had no National Cancer Institute‐Working Group 1996 criteria for treatment, and 3) had at least 1 marker of high‐risk disease 17p13−, 11q22−, 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/m2 per week ×4 doses). All patients received Pneumocystis pneumonia and herpes virus prophylaxis and were monitored for cytomegalovirus reactivation. RESULTS. Twenty‐seven 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 follow‐up, 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 high‐risk CLL. Further studies will be required to determine whether this early treatment strategy decreases morbidity and mortality for high‐risk CLL. Cancer 2008. © 2008 American Cancer Society. Early treatment of patients with high‐risk chronic lymphocytic leukemia, as defined by fluorescence in situ hybridization abnormalities (17p13− or 11q22−) or by the presence of the unmutated immunoglobulin heavy‐chain variable gene IgVH together with the expression of either CD38 or the zeta chain‐associated protein kinase ZAP‐70, resulted in high response rates with low toxicity. Responses were most durable in patients who had a complete response and a negative test for minimal residual disease.