Alemtuzumab as consolidation after a response to fludarabine is effective in purging residual disease in patients with chronic lymphocytic leukemia.
OBJECTIVE
Treatment with alemtuzumab has resulted in negative responses for minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL). In a prior analysis we demonstrated that it is possible to achieved MRD negativity, as assessed by polyclonality of immunoglobulin heavy chain after consolidation with alemtuzumab. This phase II study evaluated 34 patients with CLL who received alemtuzumab consolidation in an effort to improve the quality of their response to fludarabine-based induction. Subsequent peripheral blood stem-cell (PBSC) collection and transplantation, tolerability, and pharmacokinetics also were assessed.


METHODS
Thirty-four patients younger than 65 years who had a clinical response to fludarabine-based induction therapy received alemtuzumab 10 mg subcutaneously three times per week for 6 weeks. PBSCs were collected after mobilization with cytarabine and granulocyte colony-stimulating factor. Blood samples for pharmacokinetics study were taken between days 1 and 31.


RESULTS
The complete response rate improved from 35% after fludarabine induction to 79.4% after alemtuzumab consolidation, including 19 patients (56%) who achieved MRD negativity. The most common adverse events were injection-site reactions and fever. Cytomegalovirus reactivation occurred in 18 patients, all of whom were successfully treated with oral ganciclovir. PBSC collection was successful in 24 (92%) of 26 patients, and 18 patients underwent autologous PBSC transplantation. Alemtuzumab plasma concentrations increased gradually during the first 2 weeks and accumulated more rapidly thereafter.


CONCLUSIONS
Subcutaneously administered alemtuzumab was effective, safe, and well tolerated as consolidation therapy in patients with CLL who responded to fludarabine induction therapy. Subsequent PBSCT was feasible thereafter.
Montillo
Marco
M
Department of Hematology, Laboratory of Flow Cytometry, Transfusion Medicine Service, Niguarda Ca'Granda Hospital, Milano, Milan, Italy. marco.montillo@ospedaleniguarda.it
Tedeschi
Alessandra
A
Miqueleiz
Sara
S
Veronese
Silvio
S
Cairoli
Roberto
R
Intropido
Liliana
L
Ricci
Francesca
F
Colosimo
Anna
A
Scarpati
Barbara
B
Montagna
Michela
M
Nichelatti
Michele
M
Regazzi
Mario
M
Morra
Enrica
E
D000328:Adult; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use*; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000150:complications / Q000188:drug therapy; D005240:Feasibility Studies; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D006412:Hematopoietic Stem Cells; D006801:Humans; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual / Q000628:therapy; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine; D015774:Ganciclovir