Fludarabine followed by alemtuzumab consolidation for previously untreated chronic lymphocytic leukemia: final report of Cancer and Leukemia Group B study 19901.
The humanized anti-CD52 monoclonal antibody alemtuzumab is an effective therapy for chronic lymphocytic leukemia (CLL). We examined the impact of alemtuzumab treatment after initial fludarabine treatment for feasibility and safety. Patients (N = 85) with previously untreated symptomatic CLL received fludarabine (25 mg/m(2)/day) for 5 days every 4 weeks for four cycles followed by 2 months of observation. Patients with stable disease or better response then received alemtuzumab 30 mg three times weekly for 6 weeks either intravenously (IV; cohort 1; N = 39) or subcutaneously (SC; cohort 2; N = 20). Of the 85 evaluable patients enrolled on our study, four (5%) attained a complete response (CR) and 43 (51%) attained a partial response after fludarabine induction for an overall response rate (ORR) of 55%. Thirty-nine patients received IV alemtuzumab for consolidation with improvement in CR to 27% and ORR to 73%. Twenty patients received SC alemtuzumab consolidation with improvement in CR to 17% and ORR to 69%. Toxicity from IV alemtuzumab included infusion-related reactions and infection. Mild local inflammation was common from SC alemtuzumab but there were virtually no systemic side effects. Nine of 59 (15%) patients had cytomegalovirus (CMV) infections; one patient died. The administration of alemtuzumab as consolidation therapy following an abbreviated fludarabine induction is feasible but requires close monitoring for CMV infection and other infectious events.
The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. john.byrd@osumc.edu
John C
JC
Byrd
Bercedis L
BL
Peterson
Kanti R
KR
Rai
David
D
Hurd
Raymond
R
Hohl
Michael C
MC
Perry
Jon
J
Gockerman
Sreenivasa
S
Nattam
Richard A
RA
Larson
D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D001855:Bone Marrow Diseases / Q000139:chemically induced; D000074301:CD52 Antigen; D015331:Cohort Studies; D003586:Cytomegalovirus Infections / Q000401:mortality / Q000517:prevention & control; D005240:Feasibility Studies; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D016019:Survival Analysis; D014740:Vidarabine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000890:Anti-Infective Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D009363:Neoplasm Proteins; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine