Alemtuzumab as Treatment for Residual Disease after Chemotherapy in Patients with Chronic Lymphocytic Leukemia

Susan M. O'Brien, Hagop M. Kantarjian, Deborah A. Thomas, Jorge Cortes, Francis J. Giles, William G. Wierda, Charles A. Koller, Alessandra Ferrajoli, Mary Browning, Susan Lerner, Maher Albitar, Michael J. Keating

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202 Scopus citations

Abstract

BACKGROUND. The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy. METHODS. Forty-one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment. RESULTS. The overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow-up of 18 months. Six patients remained in disease remission between 24-38 months after therapy. Infusion-related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1-2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein-Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin. CONCLUSIONS. Alemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated.

Original languageEnglish (US)
Pages (from-to)2657-2663
Number of pages7
JournalCancer
Volume98
Issue number12
DOIs
Publication statusPublished - Dec 15 2003
Externally publishedYes

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Keywords

  • Alemtuzumab
  • CD52
  • CLL
  • Cytomegalovirus
  • Epstein-Barr virus
  • Large cell lymphoma
  • Overall response
  • Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

O'Brien, S. M., Kantarjian, H. M., Thomas, D. A., Cortes, J., Giles, F. J., Wierda, W. G., ... Keating, M. J. (2003). Alemtuzumab as Treatment for Residual Disease after Chemotherapy in Patients with Chronic Lymphocytic Leukemia. Cancer, 98(12), 2657-2663. https://doi.org/10.1002/cncr.11871