Phase II study of alemtuzumab in chronic lymphoproliferative disorders.
BACKGROUND
Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders. The authors conducted a Phase II trial to evaluate the efficacy and safety of alemtuzumab in advanced or refractory chronic lymphoproliferative disorders.


METHODS
Seventy-eight patients were enrolled. The most common diagnoses were chronic lymphocytic leukemia (n = 42 patients) and T-cell prolymphocytic leukemia (n = 18 patients). Before entering the study, the patients had received multiple therapies (median, three therapies) and the median time from diagnosis was 7 years. Alemtuzumab was given intravenously at doses of 3 mg, 10 mg, and 30 mg on 3 consecutive days, after which 30 mg was administered 3 times a week. Patients were treated for 4-12 weeks depending on disease response. All patients received prophylactic trimethoprim/sulfamethoxazole and valacyclovir.


RESULTS
The overall response rate was 35%, the complete response (CR) rate was 13%, and the partial response (PR) rate was 22%. The median duration of response was 18 months for patients achieving a CR and 7 months for patients achieving a PR. The median duration of survival was 25 months for patients who had a response and 12 months for the entire population. Normalization of the lymphocyte count was observed in 84% of patients and resolution of bone marrow involvement was observed in 49% of patients. The most common infusion-related adverse events were fever, rigors, skin rash, nausea, and dyspnea. These were most common during the first week of therapy. Hematologic toxicity was comprised of long-lasting lymphocytopenia and transient neutropenia and thrombocytopenia. Thirty-six patients (46%) experienced at least one episode of fever or infection.


CONCLUSIONS
Alemtuzumab has a high response rate in patients with chronic lymphoproliferative disorders.
Ferrajoli
Alessandra
A
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. afrrajo@mdanderson.org
O'Brien
Susan M
SM
Cortes
Jorge E
JE
Giles
Francis J
FJ
Thomas
Deborah A
DA
Faderl
Stefan
S
Kurzrock
Razelle
R
Lerner
Susan
S
Kontoyiannis
Dimitrios P
DP
Keating
Michael J
MJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host; D007239:Infections / Q000276:immunology; D007938:Leukemia / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy; D008223:Lymphoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D008875:Middle Aged; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab