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Originally published as JCO Early Release 10.1200/JCO.2005.04.021 on February 28 2005

Journal of Clinical Oncology, Vol 23, No 13 (May 1), 2005: pp. 2971-2979
© 2005 American Society of Clinical Oncology.
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Eradication of Minimal Residual Disease in B-Cell Chronic Lymphocytic Leukemia After Alemtuzumab Therapy Is Associated With Prolonged Survival

Paul Moreton, Ben Kennedy, Guy Lucas, Michael Leach, Saad M.B. Rassam, Andrew Haynes, Jane Tighe, David Oscier, Christopher Fegan, Andy Rawstron, Peter Hillmen

From the Leeds General Infirmary, Leeds; Birmingham Heartlands Hospitals, Birmingham; Nottingham City Hospital, Nottingham; Stobhill Hospital, Glasgow; Manchester Royal Infirmary, Manchester; Bournemouth Hosp, Bournemouth; Queen Mary's Hospital, Sidcup; Aberdeen Royal Infirmary, Aberdeen, United Kingdom; and Ilex Oncology, San Antonio, TX

Address reprint requests to Haematological Malignancy Diagnostic Service, Leeds Teaching Hospitals, NHS Trust, Great George St, Leeds, LS1 3EX United Kingdom; e-mail: paul-moreton{at}ntlworld.com

PURPOSE: To test whether eradication of minimal residual disease (MRD) in B-cell chronic lymphocytic leukemia (CLL) by alemtuzumab is associated with a prolongation of treatment-free and overall survival.

PATIENTS AND METHODS: Ninety-one previously treated patients with CLL (74 men and 17 women; median age, 58 years [range, 32 to 75 years]; 44 were refractory to purine analogs) received a median of 9 weeks of alemtuzumab treatment between 1996 and 2003. Regular bone marrow assessments by MRD flow cytometry were performed with the aim of eradicating detectable MRD (< 1 CLL cell in 105 normal cells).

RESULTS: Responses according to National Cancer Institute-sponsored working group response criteria were complete remission (CR) in 32 patients (36%), partial remission (PR) in 17 patients (19%), and no response (NR) in 42 patients (46%). Twenty-two (50%) of 44 purine analog-refractory patients responded to alemtuzumab. Detectable CLL was eradicated from the blood and marrow in 18 patients (20%). Median survival was significantly longer in MRD-negative patients compared with those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative CR had a longer treatment-free survival than patients with MRD-positive CRs, PR, or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13 months; NR, 6 months (P < .0001). Overall survival for the 18 patients with MRD-negative remissions was 84% at 60 months. Eight (47%) of the MRD-negative patients converted to MRD positivity at a median of 28 months.

CONCLUSION: MRD-negative remission in CLL is achievable with alemtuzumab, leading to an improved overall and treatment-free survival.

Supported by Ilex Oncology, the Leukaemia Research Fund, and Yorkshire Cancer Research.

Patients have previously been included in the following publications in a minority and with very limited, if any, survival data: Rawstron AC et al4 (18 patients); Kennedy et al14 (six patients); Keating et al13 (three patients); and Rawstron AC, Kennedy B, Moreton P, et al: Early prediction of outcome and response to alemtuzumab therapy in chronic lymphocytic leukaemia. Blood 103:2027-2031, 2004 (43 patients but no follow-up or survival data).

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


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