Activity of alemtuzumab in patients with CD52-positive acute leukemia

Raoul Tibes, Michael J. Keating, Alessandra Ferrajoli, William Wierda, Farhad Ravandi, Guillermo Garcia-Manero, Susan O'Brien, Jorge Cortes, Srdan Verstovsek, Mary L. Browning, Stefan Faderl

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Alemtuzumab is a humanized monoclonal antibody directed against the cell surface antigen CD52 and has demonstrated activity in chronic lymphocytic leukemia and other CD52-positive lymphoproliferative disorders. Because CD52 also is expressed on acute leukemic blasts, the authors investigated the safety and efficacy of alemtuzumab in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS. Fifteen patients with CD52-positive (≥20%), recurrent or refractory acute leukemia (9 patients with AML and 6 patients with ALL) received alemtuzumab at a dose of 30 mg intravenously given 3 times a week (dose escalation during Week 1) for a total of 4 to 12 weeks. RESULTS. The median age of the patients was 39 years (range, 18-71 years). Patients had received a median of 3 prior therapies (range, 1-5 prior therapies). Two patients (13%) achieved a bone marrow complete response and 1 patient achieved a substantial reduction in bone marrow blasts. No complete remissions were observed. Ten patients developed disease progression while on study. Alemtuzumab was myelosuppressive in nearly all patients. Infusion-related toxicities were common, but usually did not exceed Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Infectious episodes occurred in 13 patients (87%) and included pneumonia (6 patients), bacteremia (11 patients), fungemia (2 patients), and cytomegalovirus reactivation (2 patients). CONCLUSIONS. Single-agent alemtuzumab was found to have limited activity in recurrent or refractory acute leukemia. An evaluation in patients with a better prognosis, in combination with other agents or as part of consolidation therapy, is warranted.

Original languageEnglish (US)
Pages (from-to)2645-2651
Number of pages7
JournalCancer
Volume106
Issue number12
DOIs
StatePublished - Jun 15 2006
Externally publishedYes

Fingerprint

Leukemia
alemtuzumab
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Acute Myeloid Leukemia
Bone Marrow
Fungemia
Antibodies, Monoclonal, Humanized
Lymphoproliferative Disorders
National Cancer Institute (U.S.)
B-Cell Chronic Lymphocytic Leukemia
Surface Antigens
Bacteremia
Cytomegalovirus
Disease Progression
Pneumonia
Therapeutics
Safety

Keywords

  • Acute lymphoblastic leukemia
  • Acute myeloid leukemia
  • Alemtuzumab
  • Monoclonal antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tibes, R., Keating, M. J., Ferrajoli, A., Wierda, W., Ravandi, F., Garcia-Manero, G., ... Faderl, S. (2006). Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer, 106(12), 2645-2651. https://doi.org/10.1002/cncr.21901

Activity of alemtuzumab in patients with CD52-positive acute leukemia. / Tibes, Raoul; Keating, Michael J.; Ferrajoli, Alessandra; Wierda, William; Ravandi, Farhad; Garcia-Manero, Guillermo; O'Brien, Susan; Cortes, Jorge; Verstovsek, Srdan; Browning, Mary L.; Faderl, Stefan.

In: Cancer, Vol. 106, No. 12, 15.06.2006, p. 2645-2651.

Research output: Contribution to journalArticle

Tibes, R, Keating, MJ, Ferrajoli, A, Wierda, W, Ravandi, F, Garcia-Manero, G, O'Brien, S, Cortes, J, Verstovsek, S, Browning, ML & Faderl, S 2006, 'Activity of alemtuzumab in patients with CD52-positive acute leukemia', Cancer, vol. 106, no. 12, pp. 2645-2651. https://doi.org/10.1002/cncr.21901
Tibes R, Keating MJ, Ferrajoli A, Wierda W, Ravandi F, Garcia-Manero G et al. Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer. 2006 Jun 15;106(12):2645-2651. https://doi.org/10.1002/cncr.21901
Tibes, Raoul ; Keating, Michael J. ; Ferrajoli, Alessandra ; Wierda, William ; Ravandi, Farhad ; Garcia-Manero, Guillermo ; O'Brien, Susan ; Cortes, Jorge ; Verstovsek, Srdan ; Browning, Mary L. ; Faderl, Stefan. / Activity of alemtuzumab in patients with CD52-positive acute leukemia. In: Cancer. 2006 ; Vol. 106, No. 12. pp. 2645-2651.
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abstract = "BACKGROUND. Alemtuzumab is a humanized monoclonal antibody directed against the cell surface antigen CD52 and has demonstrated activity in chronic lymphocytic leukemia and other CD52-positive lymphoproliferative disorders. Because CD52 also is expressed on acute leukemic blasts, the authors investigated the safety and efficacy of alemtuzumab in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS. Fifteen patients with CD52-positive (≥20{\%}), recurrent or refractory acute leukemia (9 patients with AML and 6 patients with ALL) received alemtuzumab at a dose of 30 mg intravenously given 3 times a week (dose escalation during Week 1) for a total of 4 to 12 weeks. RESULTS. The median age of the patients was 39 years (range, 18-71 years). Patients had received a median of 3 prior therapies (range, 1-5 prior therapies). Two patients (13{\%}) achieved a bone marrow complete response and 1 patient achieved a substantial reduction in bone marrow blasts. No complete remissions were observed. Ten patients developed disease progression while on study. Alemtuzumab was myelosuppressive in nearly all patients. Infusion-related toxicities were common, but usually did not exceed Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Infectious episodes occurred in 13 patients (87{\%}) and included pneumonia (6 patients), bacteremia (11 patients), fungemia (2 patients), and cytomegalovirus reactivation (2 patients). CONCLUSIONS. Single-agent alemtuzumab was found to have limited activity in recurrent or refractory acute leukemia. An evaluation in patients with a better prognosis, in combination with other agents or as part of consolidation therapy, is warranted.",
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AU - Tibes, Raoul

AU - Keating, Michael J.

AU - Ferrajoli, Alessandra

AU - Wierda, William

AU - Ravandi, Farhad

AU - Garcia-Manero, Guillermo

AU - O'Brien, Susan

AU - Cortes, Jorge

AU - Verstovsek, Srdan

AU - Browning, Mary L.

AU - Faderl, Stefan

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N2 - BACKGROUND. Alemtuzumab is a humanized monoclonal antibody directed against the cell surface antigen CD52 and has demonstrated activity in chronic lymphocytic leukemia and other CD52-positive lymphoproliferative disorders. Because CD52 also is expressed on acute leukemic blasts, the authors investigated the safety and efficacy of alemtuzumab in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS. Fifteen patients with CD52-positive (≥20%), recurrent or refractory acute leukemia (9 patients with AML and 6 patients with ALL) received alemtuzumab at a dose of 30 mg intravenously given 3 times a week (dose escalation during Week 1) for a total of 4 to 12 weeks. RESULTS. The median age of the patients was 39 years (range, 18-71 years). Patients had received a median of 3 prior therapies (range, 1-5 prior therapies). Two patients (13%) achieved a bone marrow complete response and 1 patient achieved a substantial reduction in bone marrow blasts. No complete remissions were observed. Ten patients developed disease progression while on study. Alemtuzumab was myelosuppressive in nearly all patients. Infusion-related toxicities were common, but usually did not exceed Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Infectious episodes occurred in 13 patients (87%) and included pneumonia (6 patients), bacteremia (11 patients), fungemia (2 patients), and cytomegalovirus reactivation (2 patients). CONCLUSIONS. Single-agent alemtuzumab was found to have limited activity in recurrent or refractory acute leukemia. An evaluation in patients with a better prognosis, in combination with other agents or as part of consolidation therapy, is warranted.

AB - BACKGROUND. Alemtuzumab is a humanized monoclonal antibody directed against the cell surface antigen CD52 and has demonstrated activity in chronic lymphocytic leukemia and other CD52-positive lymphoproliferative disorders. Because CD52 also is expressed on acute leukemic blasts, the authors investigated the safety and efficacy of alemtuzumab in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). METHODS. Fifteen patients with CD52-positive (≥20%), recurrent or refractory acute leukemia (9 patients with AML and 6 patients with ALL) received alemtuzumab at a dose of 30 mg intravenously given 3 times a week (dose escalation during Week 1) for a total of 4 to 12 weeks. RESULTS. The median age of the patients was 39 years (range, 18-71 years). Patients had received a median of 3 prior therapies (range, 1-5 prior therapies). Two patients (13%) achieved a bone marrow complete response and 1 patient achieved a substantial reduction in bone marrow blasts. No complete remissions were observed. Ten patients developed disease progression while on study. Alemtuzumab was myelosuppressive in nearly all patients. Infusion-related toxicities were common, but usually did not exceed Grade 2 (according to the National Cancer Institute Common Toxicity Criteria). Infectious episodes occurred in 13 patients (87%) and included pneumonia (6 patients), bacteremia (11 patients), fungemia (2 patients), and cytomegalovirus reactivation (2 patients). CONCLUSIONS. Single-agent alemtuzumab was found to have limited activity in recurrent or refractory acute leukemia. An evaluation in patients with a better prognosis, in combination with other agents or as part of consolidation therapy, is warranted.

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KW - Acute myeloid leukemia

KW - Alemtuzumab

KW - Monoclonal antibodies

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