Originally published as JCO Early Release 10.1200/JCO.2007.12.9098 on November 5 2007

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Alemtuzumab Compared With Chlorambucil As First-Line Therapy for Chronic Lymphocytic Leukemia

Peter Hillmen, Aleksander B. Skotnicki, Tadeusz Robak, Branimir Jaksic, Anna Dmoszynska, Jingyang Wu, Cynthia Sirard, Jiri Mayer

From the Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom; Jagiellionian University Collegium Medicum, Krakow; Kopernik Memorial Hospital, Lodz; Clinical Hospital No 1, Lublin, Poland; Clinical Hospital Merkur, Zagreb, Croatia; Genzyme Corp, Cambridge, MA; and the University Hospital Brno, Brno, Czech Republic

Address reprint requests to Peter Hillmen, MD, PhD, Leeds Teaching Hospitals National Health Service Trust, Leeds General Infirmary, Leeds, United Kingdom; e-mail: peter.hillmen{at}nhs.net

Purpose: We conducted a randomized trial to evaluate the efficacy and safety of intravenous alemtuzumab compared with chlorambucil in first-line treatment of chronic lymphocytic leukemia (CLL).

Patients and Methods: Patients received alemtuzumab (30 mg three times per week, for up to 12 weeks) or chlorambucil (40 mg/m² every 28 days, for up to 12 months). The primary end point was progression-free survival (PFS). Secondary end points included overall response rate (ORR), complete response (CR), time to alternative therapy, safety, and overall survival.

Results: We randomly assigned 297 patients, 149 to alemtuzumab and 148 to chlorambucil. Alemtuzumab had superior PFS, with a 42% reduction in risk of progression or death (hazard ratio [HR] = 0.58; P = .0001), and a median time to alternative treatment of 23.3 versus 14.7 months for chlorambucil (HR = 0.54; P = .0001). The ORR was 83% with alemtuzumab (24% CR) versus 55% with chlorambucil (2% CR); differences in ORR and CR were highly statistically significant (P < .0001). Elimination of minimal residual disease occurred in 11 of 36 complete responders to alemtuzumab versus none to chlorambucil. Adverse events profiles were similar, except for more infusion-related and cytomegalovirus (CMV) events with alemtuzumab and more nausea and vomiting with chlorambucil. CMV events had no apparent impact on efficacy.

Conclusion: As first-line treatment for patients with CLL, alemtuzumab demonstrated significantly improved PFS, time to alternative treatment, ORR and CR, and minimal residual disease–negative remissions compared with chlorambucil, with predictable and manageable toxicity.

published online ahead of print at www.jco.org on November 5, 2007.

Supported by Genzyme Corp, Cambridge, MA.

Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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