A pilot trial of rituximab and alemtuzumab combination therapy in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL).
The treatment of patients with chronic lymphocytic leukemia (CLL) who fail purine analogues is sub optimal. CLL lymphocytes express two antigens, namely CD 20 and CD 52, for which monoclonal antibodies are readily available. Rituximab is a chimeric monoclonal antibody targeted against CD 20, which has some activity in refractory CLL, with primary effect on nodal disease. Alemtuzumab is a humanized anti-CD 52 antibody that is approved for the treatment of CLL in patients who fail alkylating agents and purine analogues. Alemtuzumab has better activity in the peripheral blood and the bone marrow compared to nodal disease. We investigated whether combining both antibodies is safe in refractory CLL. Both antibodies were given to a total of 12 patients divided into 3 cohorts with escalating alemtuzumab doses (3 mg, 10 mg, and 30 mg). The combination was proven to be safe, not toxic, feasible, and active. One patient attained PR by NCI criteria while all other patients had stable disease lasting a median of 101.5 days. All patients normalized their peripheral lymphocytosis within a median of 23.5 days. No treatment-related mortality was identified. No CMV reactivation occurred. Additional studies are needed to investigate the clinical significance of such a combination in this patient population, and whether this combination can be administered safely with systemic chemotherapy. These studies are currently underway.
Nabhan
Chadi
C
Oncology Specialists, S.C. Lutheran General Hospital Cancer Care Center, Park Ridge, Illinois 60068, USA. cnabhan@oncmed.net
Patton
David
D
Gordon
Leo I
LI
Riley
Mary B
MB
Kuzel
Timothy
T
Tallman
Martin S
MS
Rosen
Steven T
ST
D000368:Aged; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm / Q000008:administration & dosage*; D015703:Antigens, CD / Q000276:immunology; D018951:Antigens, CD20 / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000074301:CD52 Antigen; D015331:Cohort Studies; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000628:therapy; D008218:Lymphocytosis; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence; D000069283:Rituximab; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D000074323:Alemtuzumab; D000069283:Rituximab