Alemtuzumab As Consolidation After a Response to Fludarabine Is Effective in Purging Residual Disease in Patients With Chronic Lymphocytic Leukemia Marco Montillo, Alessandra Tedeschi, Sara Miqueleiz, Silvio Veronese, Roberto Cairoli, Liliana Intropido, Francesca Ricci, Anna Colosimo, Barbara Scarpati, Michela Montagna, Michele Nichelatti, Mario Regazzi, and Enrica Morra A B S T R A C T Purpose Treatment with alemtuzumab has resulted in negative responses for minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL). In a prior analysis we demonstrated that it is possible to achieved MRD negativity, as assessed by polyclonality of immunoglobulin heavy chain after consolidation with alemtuzumab. This phase II study evaluated 34 patients with CLL who received alemtuzumab consolidation in an effort to improve the quality of their response to fludarabine-based induction. Subsequent peripheral blood stem-cell (PBSC) collection and transplantation, tolerability, and pharmacokinetics also were assessed. Patients and Methods Thirty-four patients younger than 65 years who had a clinical response to fludarabine-based induction therapy received alemtuzumab 10 mg subcutaneously three times per week for 6 weeks. PBSCs were collected after mobilization with cytarabine and granulocyte colony- stimulating factor. Blood samples for pharmacokinetics study were taken between days 1 and 31. Results The complete response rate improved from 35% after fludarabine induction to 79.4% after alemtuzumab consolidation, including 19 patients (56%) who achieved MRD negativity. The most common adverse events were injection-site reactions and fever. Cytomegalovirus reactivation occurred in 18 patients, all of whom were successfully treated with oral ganciclovir. PBSC collection was successful in 24 (92%) of 26 patients, and 18 patients underwent autologous PBSC transplantation. Alemtuzumab plasma concentrations increased gradually during the first 2 weeks and accumulated more rapidly thereafter. Conclusion Subcutaneously administered alemtuzumab was effective, safe, and well tolerated as consolida- tion therapy in patients with CLL who responded to fludarabine induction therapy. Subsequent PBSCT was feasible thereafter. J Clin Oncol 24:2337-2342. © 2006 by American Society of Clinical Oncology INTRODUCTION Chronic lymphocytic leukemia (CLL) is a B-cell he- matologic malignancy that affects approximately 120,000 persons in the United States, Europe, and Australia each year. 1 Although CLL traditionally has been perceived as a disease of the elderly, with fewer than 25% of cases occurring in individuals younger than age 65 years, 2 the rate of diagnosis among younger patients is increasing as a result of more prevalent use of routine blood testing. 3 Because early therapeutic interventions for asymptomatic CLL have not been shown to improve survival, therapy is generally reserved for patients with symptomatic disease. 4 Fludarabine, the current standard first-line therapy for CLL, is associated with substantially better clinical response rates com- pared with previous alkylating agent– based thera- pies. Despite the improved response rate, the duration of overall survival or quality of life–ad- justed survival has been only moderately prolonged at best. 5 The existence and level of minimal residual dis- ease (MRD) is a powerful prognostic factor for re- lapse, and elimination of MRD in the bone marrow correlates well with longer overall survival com- pared with patients who do not achieve MRD nega- tivity. 6 Consequently, new treatment approaches for From the Department of Hematology, Department of Pathology, Laboratory of Flow Cytometry, Transfusion Medicine Service, Niguarda Ca’Granda Hospital, Milano; and the Department of Pharma- cology IRCCS, Istituto di Ricovero e Cura a Carattere Scientifico-Policlinico S. Matteo, Pavia, Italy. Submitted October 13, 2005; accepted March 3, 2006. Authors’ disclosures of potential con- flicts of interest and author contribu- tions are found at the end of this article. Address reprint requests to Marco Montillo, MD, Dipartimento di On colo- gia Ematologia, Divisione di Ematologia, Ospedale Niguarda Ca’Granda, Piazza Ospedale Maggiore 3, 20162, Milan, Italy; e-mail: marco.montillo@ ospedaleniguarda.it. © 2006 by American Society of Clinical Oncology 0732-183X/06/2415-2337/$20.00 DOI: 10.1200/JCO.2005.04.6037 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 24  NUMBER 15  MAY 20 2006 2337 Downloaded from jco.ascopubs.org on February 23, 2016. For personal use only. No other uses without permission. Copyright © 2006 American Society of Clinical Oncology. All rights reserved.