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.
Leonard
John P
JP
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
Coleman
Morton
M
Ketas
Jamie C
JC
Chadburn
Amy
A
Furman
Richard
R
Schuster
Michael W
MW
Feldman
Eric J
EJ
Ashe
Michelle
M
Schuster
Stephen J
SJ
Wegener
William A
WA
Hansen
Hans J
HJ
Ziccardi
Heather
H
Eschenberg
Michael
M
Gayko
Urte
U
Fields
Scott Z
SZ
Cesano
Alessandra
A
Goldenberg
David M
DM
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