Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin's lymphoma: phase I/II clinical trial results.
OBJECTIVE
We conducted a single-center, dose-escalation study evaluating the safety, pharmacokinetics, and efficacy of epratuzumab, an anti-CD22 humanized monoclonal antibody, in patients with aggressive non-Hodgkin's lymphoma.


METHODS
Epratuzumab was administered once weekly for 4 weeks at 120-1000-mg/m2 doses to 56 patients [most (n = 35) with diffuse large B-cell lymphoma].


RESULTS
Patients were heavily pretreated (median, 4 prior therapies), 25% received prior high-dose chemotherapy with stem cell transplant, and 84% had bulky disease (> or =5 cm). Epratuzumab was well tolerated, with no dose-limiting toxicity. Most (95%) infusions were completed within 1 h. The mean serum half-life was 23.9 days. Across all dose levels and histologies, objective responses (ORs) were observed in five patients (10%; 95% confidence interval, 3-21%), including three complete responses. In patients with diffuse large B-cell lymphoma, 15% had ORs. Overall, 11 (20%) patients experienced some tumor mass reduction. Median duration of OR was 26.3 weeks, and median time to progression for responders was 35 weeks. Two responses are ongoing at > or =34 months, including one rituximab-refractory patient.


CONCLUSIONS
These data demonstrate that epratuzumab has a good safety profile and exerts antitumor activity in aggressive non-Hodgkin's lymphoma at doses of > or =240 mg/m2, thus warranting further evaluation in this clinical setting.
Division of Hematology and Oncology, Center for Lymphoma and Myeloma, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, New York 10021, USA. jpleonar@med.cornell.edu
John P
JP
Leonard
Morton
M
Coleman
Jamie C
JC
Ketas
Amy
A
Chadburn
Richard
R
Furman
Michael W
MW
Schuster
Eric J
EJ
Feldman
Michelle
M
Ashe
Stephen J
SJ
Schuster
William A
WA
Wegener
Hans J
HJ
Hansen
Heather
H
Ziccardi
Michael
M
Eschenberg
Urte
U
Gayko
Scott Z
SZ
Fields
Alessandra
A
Cesano
David M
DM
Goldenberg
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000276:immunology; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D015815:Cell Adhesion Molecules / Q000276:immunology; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D037102:Lectins / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012449:Safety; D051918:Sialic Acid Binding Ig-like Lectin 2; D013997:Time Factors
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D037102:Lectins; D051918:Sialic Acid Binding Ig-like Lectin 2; C448700:epratuzumab