Alemtuzumab treatment of intermediate-1 myelodysplasia patients is associated with sustained improvement in blood counts and cytogenetic remissions.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Alemtuzumab is safe and active in MDS and may be an attractive alternative to ATG in selected patients likely to respond to IST.
Hematology Branch, National Heart, Lung, and Blood Institute, Bldg 10 CRC 4-5230, Bethesda, MD 20892, USA. sloande@nhlbi.nih.gov
Elaine M
EM
Sloand
Matthew J
MJ
Olnes
Aarthie
A
Shenoy
Barbara
B
Weinstein
Carol
C
Boss
Kelsey
K
Loeliger
Colin O
CO
Wu
Kenneth
K
More
A John
AJ
Barrett
Phillip
P
Scheinberg
Neal S
NS
Young
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality; D056687:Off-Label Use; D010865:Pilot Projects; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab