Originally published as JCO Early Release 10.1200/JCO.2005.13.821 on June 13 2005

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leonard, J. P. Articles by Goldenberg, D. M. Search for Related Content PubMed PubMed Citation Articles by Leonard, J. P. Articles by Goldenberg, D. M. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Cancer Chemotherapy Social Bookmarking                            What's this?

Combination Antibody Therapy With Epratuzumab and Rituximab in Relapsed or Refractory Non-Hodgkin's Lymphoma

From the Center for Lymphoma and Myeloma, Division of Hematology and Medical Oncology, and Department of Pathology, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY; Immunomedics Inc, Morris Plains, NJ; and Garden State Cancer Center, Center for Molecular Medicine and Immunology, Belleville, NJ

Address reprint requests to John P. Leonard, Center for Lymphoma and Myeloma, and Division of Hematology and Oncology, Weill Medical College of Cornell University and New York Presbyterian Hospital, 520 E 70th St, New York, NY 10021; e-mail: jpleonar{at}med.cornell.edu

PURPOSE: To explore the safety and therapeutic activity of combination anti–B-cell monoclonal antibody therapy in non-Hodgkin's lymphoma (NHL).

PATIENTS AND METHODS: Twenty-three patients with recurrent B-cell lymphoma received anti-CD22 epratuzumab 360 mg/m² and anti-CD20 rituximab 375 mg/m² monoclonal antibodies weekly for four doses each. Sixteen patients had indolent histologies (15 with follicular lymphoma) and seven had aggressive NHL (all diffuse large B-cell lymphoma [DLBCL]). Indolent patients had received a median of one (range, one to six) prior treatment, with 31% refractory to their last therapy and 81% with high-risk Follicular Lymphoma International Prognostic Index scores. Patients with DLBCL had a median of three (range, one to eight) prior regimens (14% resistant to last treatment) and 71% had high intermediate–risk or high-risk International Prognostic Index scores. All patients were rituximab naïve.

RESULTS: Treatment was well tolerated, with toxicities principally infusion-related and predominantly grade 1 or 2. Ten (67%) patients with follicular NHL achieved an objective response (OR), including nine of 15 (60%) with complete responses (CRs and unconfirmed CRs). Four of six assessable patients (67%) with DLBCL achieved an OR, including three (50%) CRs. Median time to progression for all indolent NHL patients was 17.8 months.

CONCLUSION: The full-dose combination of epratuzumab with rituximab was well tolerated and had significant clinical activity in NHL, suggesting that this combination should be tested in comparison with single-agent treatment.

Supported by a K23 award from the National Institutes of Health (RR16814), and grants from the Cornell Center for Aging Research and Clinical Care, the Lymphoma Research Foundation, the Dorothy Rodbell Cohen Foundation, and the Brian Rooney Fund of the Lymphoma Foundation, as well as research grants from Immunomedics Inc.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				E. A. Rossi, D. M. Goldenberg, T. M. Cardillo, R. Stein, and C.-H. Chang Hexavalent bispecific antibodies represent a new class of anticancer therapeutics: 1. Properties of anti-CD20/CD22 antibodies in lymphoma Blood, June 11, 2009; 113(24): 6161 - 6171. [Abstract] [Full Text] [PDF]

				D. M. Goldenberg, E. A. Rossi, R. Stein, T. M. Cardillo, M. S. Czuczman, F. J. Hernandez-Ilizaliturri, H. J. Hansen, and C.-H. Chang Properties and structure-function relationships of veltuzumab (hA20), a humanized anti-CD20 monoclonal antibody Blood, January 29, 2009; 113(5): 1062 - 1070. [Abstract] [Full Text] [PDF]

				B. D. Cheson and J. P. Leonard Monoclonal Antibody Therapy for B-Cell Non-Hodgkin's Lymphoma N. Engl. J. Med., August 7, 2008; 359(6): 613 - 626. [Full Text] [PDF]

				E. A. Raetz, M. S. Cairo, M. J. Borowitz, S. M. Blaney, M. D. Krailo, T. A. Leil, J. M. Reid, D. M. Goldenberg, W. A. Wegener, W. L. Carroll, et al. Chemoimmunotherapy Reinduction With Epratuzumab in Children With Acute Lymphoblastic Leukemia in Marrow Relapse: A Children's Oncology Group Pilot Study J. Clin. Oncol., August 1, 2008; 26(22): 3756 - 3762. [Abstract] [Full Text] [PDF]

				F. Buchegger, O. W. Press, A. B. Delaloye, and N. Ketterer Radiolabeled and Native Antibodies and the Prospect of Cure of Follicular Lymphoma Oncologist, June 1, 2008; 13(6): 657 - 667. [Abstract] [Full Text] [PDF]

				Z. Qu, D. M. Goldenberg, T. M. Cardillo, V. Shi, H. J. Hansen, and C.-H. Chang Bispecific anti-CD20/22 antibodies inhibit B-cell lymphoma proliferation by a unique mechanism of action Blood, February 15, 2008; 111(4): 2211 - 2219. [Abstract] [Full Text] [PDF]

				W. J. G. Oyen, L. Bodei, F. Giammarile, H. R. Maecke, J. Tennvall, M. Luster, and B. Brans Targeted therapy in nuclear medicine current status and future prospects Ann. Onc., November 1, 2007; 18(11): 1782 - 1792. [Abstract] [Full Text] [PDF]

				J. M. Rowe and A. H. Goldstone How I treat acute lymphocytic leukemia in adults Blood, October 1, 2007; 110(7): 2268 - 2275. [Abstract] [Full Text] [PDF]

				P. Martin, R. R. Furman, M. Coleman, and J. P. Leonard Phase I to III Trials of Anti B Cell Therapy in Non Hodgkin's Lymphoma Clin. Cancer Res., September 15, 2007; 13(18): 5636s - 5642s. [Abstract] [Full Text] [PDF]

				C. Larbouret, B. Robert, I. Navarro-Teulon, S. Thezenas, M.-Z. Ladjemi, S. Morisseau, E. Campigna, F. Bibeau, J.-P. Mach, A. Pelegrin, et al. In vivo Therapeutic Synergism of Anti-Epidermal Growth Factor Receptor and Anti-HER2 Monoclonal Antibodies against Pancreatic Carcinomas Clin. Cancer Res., June 1, 2007; 13(11): 3356 - 3362. [Abstract] [Full Text] [PDF]

				P. R. Hess, C. Barnes, M. D. Woolard, M. D. L. Johnson, J. M. Cullen, E. J. Collins, and J. A. Frelinger Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin Blood, April 15, 2007; 109(8): 3300 - 3307. [Abstract] [Full Text] [PDF]

				D. G. Maloney Follicular NHL: From Antibodies and Vaccines to Graft-versus-Lymphoma Effects Hematology, January 1, 2007; 2007(1): 226 - 232. [Abstract] [Full Text] [PDF]

				B. E. Collins, O. Blixt, S. Han, B. Duong, H. Li, J. K. Nathan, N. Bovin, and J. C. Paulson High-Affinity Ligand Probes of CD22 Overcome the Threshold Set by cis Ligands to Allow for Binding, Endocytosis, and Killing of B Cells. J. Immunol., September 1, 2006; 177(5): 2994 - 3003. [Abstract] [Full Text] [PDF]

				S. J. Strauss, F. Morschhauser, J. Rech, R. Repp, P. Solal-Celigny, P. L. Zinzani, A. Engert, B. Coiffier, D. F. Hoelzer, W. A. Wegener, et al. Multicenter Phase II Trial of Immunotherapy With the Humanized Anti-CD22 Antibody, Epratuzumab, in Combination With Rituximab, in Refractory or Recurrent Non-Hodgkin's Lymphoma J. Clin. Oncol., August 20, 2006; 24(24): 3880 - 3886. [Abstract] [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]

				J. F. DiJoseph, M. M. Dougher, L. B. Kalyandrug, D. C. Armellino, E. R. Boghaert, P. R. Hamann, J. K. Moran, and N. K. Damle Antitumor Efficacy of a Combination of CMC-544 (Inotuzumab Ozogamicin), a CD22-Targeted Cytotoxic Immunoconjugate of Calicheamicin, and Rituximab against Non-Hodgkin's B-Cell Lymphoma Clin. Cancer Res., January 1, 2006; 12(1): 242 - 249. [Abstract] [Full Text] [PDF]