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.
Byrd
John C
JC
The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. john.byrd@osumc.edu
Peterson
Bercedis L
BL
Rai
Kanti R
KR
Hurd
David
D
Hohl
Raymond
R
Perry
Michael C
MC
Gockerman
Jon
J
Nattam
Sreenivasa
S
Larson
Richard A
RA
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