Alemtuzumab Treatment of Intermediate-1 Myelodysplasia Patients Is Associated With Sustained Improvement in Blood Counts and Cytogenetic Remissions

• Published in: Journal of clinical oncology Vol. 28; no. 35; pp. 5166 - 5173
• Main Authors: SLOAND, Elaine M, OLNES, Matthew J, YOUNG, Neal S, SHENOY, Aarthie, WEINSTEIN, Barbara, BOSS, Carol, LOELIGER, Kelsey, WU, Colin O, MORE, Kenneth, BARRETT, A. John, SCHEINBERG, Phillip
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 10-12-2010
• Subjects: Adult; Aged; Alemtuzumab; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - therapeutic use; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Female; Hematologic and hematopoietic diseases; Humans; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - mortality; Off-Label Use; Original Reports; Pilot Projects; Treatment Outcome; Tumors; Young Adult; Antineoplastic agent; Human; Cancerology; Treatment; Cytogenetics; Remission; Malignant hemopathy; Alemtuzumab; Monoclonal antibody; Blood cell count; Myelodysplastic syndrome; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2010.29.7010

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and progression to leukemia. Clinical and experimental evidence suggests an immune-mediated pathophysiology in some patients, in whom immunosuppressive therapy (IST) with horse antithymocyte globulin (h-ATG) and cyclosporine (CsA) can be effective. Because of the toxicities associated with h-ATG/CsA, we investigated an alternative regimen with alemtuzumab in MDS.
We conducted a nonrandomized, off-label, pilot, phase I/II study of alemtuzumab monotherapy in patients with MDS who were judged likely to respond to IST based on the following criteria: HLA-DR15-negative patients whose age plus the number of months of RBC transfusion dependence (RCTD) was less than 58; and HLA-DR15-positive patients whose age plus RCTD was less than 72. In total, 121 patients with MDS were screened, of whom 32 met eligibility criteria to receive alemtuzumab 10 mg/d intravenously for 10 days. Primary end points were hematologic responses at 3, 6, and 12 months after alemtuzumab.
Seventeen (77%) of 22 evaluable intermediate-1 patients and four (57%) of seven evaluable intermediate-2 patients responded to treatment with a median time to response of 3 months. Four of seven evaluable responders with cytogenetic abnormalities before treatment had normal cytogenetics by 1 year after treatment. Five (56%) of nine responding patients evaluable at 12 months had normal blood counts, and seven (78%) of nine patients were transfusion independent.
Alemtuzumab is safe and active in MDS and may be an attractive alternative to ATG in selected patients likely to respond to IST.