Durable hematologic complete response and suppression of HTLV-1 viral load following alemtuzumab in zidovudine/IFN-{alpha}-refractory adult T-cell leukemia.
Adult T-cell leukemia (ATL) is a highly chemoresistant and usually fatal T-cell malignancy due to the human T-cell lymphotropic virus-1 (HTLV-1). After chemotherapy failure, antiretrovirals and interferon-alpha (IFN-alpha) produce brief responses followed by progression and death. More effective agents and new approaches to detect and treat minimal residual disease are needed. ATL cells express CD52, the target of the antibody alemtuzumab, which is active in a preclinical model of ATL and is cytotoxic for p53-deficient cells. A patient with refractory chronic ATL in transformation achieved longer than a 1-year complete hematologic response following 12 weeks of outpatient subcutaneous alemtuzumab. Persistent suppression of HTLV-1 viral load, even at recovery of T cells, after alemtuzumab and efficient in vitro complement-mediated cytotoxicity of primary ATL cells with mutated TP53 were observed. The unprecedented response and the profound suppression of HTLV-1 viral load observed in this patient suggest that further clinical investigation of alemtuzumab in ATL is warranted.
Mone
Andrew
A
Division of Hematology-Oncology, Department of Internal Medicine, The Comprehensive Cancer Center, The Ohio State University, Columbus, 43210, USA.
Puhalla
Shannon
S
Whitman
Susan
S
Baiocchi
Robert A
RA
Cruz
Julio
J
Vukosavljevic
Tamara
T
Banks
Amy
A
Eisenbeis
Charles F
CF
Byrd
John C
JC
Caligiuri
Michael A
MA
Porcu
Pierluigi
P
D000074323:Alemtuzumab; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000074301:CD52 Antigen; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D015368:Human T-lymphotropic virus 1; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage*; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D008875:Middle Aged; D020127:Recovery of Function / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000378:metabolism; D019562:Viral Load / Q000379:methods; D015215:Zidovudine / Q000008:administration & dosage*
D019380:Anti-HIV Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D016898:Interferon-alpha; D016159:Tumor Suppressor Protein p53; D000074323:Alemtuzumab; D015215:Zidovudine