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Journal of Clinical Oncology, Vol 16, 2825-2833, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program

P McLaughlin, AJ Grillo-Lopez, BK Link, R Levy, MS Czuczman, ME Williams, MR Heyman, I Bence-Bruckler, CA White, F Cabanillas, V Jain, AD Ho, J Lister, K Wey, D Shen and BK Dallaire
Department of Hematology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. pmclaugh@notes.mdacc.tmc.edu

PURPOSE: The CD20 antigen is expressed on more than 90% of B-cell lymphomas. It is appealing for targeted therapy, because it does not shed or modulate. A chimeric monoclonal antibody more effectively mediates host effector functions and is itself less immunogenic than are murine antibodies. PATIENTS AND METHODS: This was a multiinstitutional trial of the chimeric anti-CD20 antibody, IDEC-C2B8. Patients with relapsed low grade or follicular lymphoma received an outpatient treatment course of IDEC-C2B8 375 mg/m2 intravenously weekly for four doses. RESULTS: From 31 centers, 166 patients were entered. Of this intent-to-treat group, 48% responded. With a median follow-up duration of 11.8 months, the projected median time to progression for responders is 13.0 months. Serum antibody levels were sustained longer after the fourth infusion than after the first, and were higher in responders and in patients with lower tumor burden. The majority of adverse events occurred during the first infusion and were grade 1 or 2; fever and chills were the most common events. Only 12% of patients had grade 3 and 3% grade 4 toxicities. A human antichimeric antibody was detected in only one patient. CONCLUSION: The response rate of 48% with IDEC-C2B8 is comparable to results with single-agent cytotoxic chemotherapy. Toxicity was mild. Attention needs to be paid to the rate of antibody infusion, with titration according to toxicity. Further investigation of this agent is warranted, including its use in conjunction with standard chemotherapy.
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E. Hatef, D. Roberts, P. McLaughlin, B. Pro, and B. Esmaeli
Prevalence and Nature of Systemic Involvement and Stage at Initial Examination in Patients With Orbital and Ocular Adnexal Lymphoma
Arch Ophthalmol, December 1, 2007; 125(12): 1663 - 1667.
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D. Daniel, B. Yang, D. A. Lawrence, K. Totpal, I. Balter, W. P. Lee, A. Gogineni, M. J. Cole, S. F. Yee, S. Ross, et al.
Cooperation of the proapoptotic receptor agonist rhApo2L/TRAIL with the CD20 antibody rituximab against non-Hodgkin lymphoma xenografts
Blood, December 1, 2007; 110(12): 4037 - 4046.
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G. Ungerechts, C. Springfeld, M. E. Frenzke, J. Lampe, P. B. Johnston, W. B. Parker, E. J. Sorscher, and R. Cattaneo
Lymphoma Chemovirotherapy: CD20-Targeted and Convertase-Armed Measles Virus Can Synergize with Fludarabine
Cancer Res., November 15, 2007; 67(22): 10939 - 10947.
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T.-H. Huang, K. R. Chintalacharuvu, and S. L. Morrison
Targeting IFN-{alpha} to B Cell Lymphoma by a Tumor-Specific Antibody Elicits Potent Antitumor Activities
J. Immunol., November 15, 2007; 179(10): 6881 - 6888.
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J. P. Leonard, B. K. Link, C. Emmanouilides, S. A. Gregory, D. Weisdorf, J. Andrey, J. Hainsworth, J. A. Sparano, D. E. Tsai, S. Horning, et al.
Phase I Trial of Toll-Like Receptor 9 Agonist PF-3512676 with and Following Rituximab in Patients with Recurrent Indolent and Aggressive Non Hodgkin's Lymphoma
Clin. Cancer Res., October 15, 2007; 13(20): 6168 - 6174.
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X. Zhao, R. Lapalombella, T. Joshi, C. Cheney, A. Gowda, M. S. Hayden-Ledbetter, P. R. Baum, T. S. Lin, D. Jarjoura, A. Lehman, et al.
Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical
Blood, October 1, 2007; 110(7): 2569 - 2577.
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Y. Li, M. E. Williams, J. B. Cousar, A. W. Pawluczkowycz, M. A. Lindorfer, and R. P. Taylor
Rituximab-CD20 Complexes Are Shaved from Z138 Mantle Cell Lymphoma Cells in Intravenous and Subcutaneous SCID Mouse Models
J. Immunol., September 15, 2007; 179(6): 4263 - 4271.
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C. M. Paulos, A. Kaiser, C. Wrzesinski, C. S. Hinrichs, L. Cassard, A. Boni, P. Muranski, L. Sanchez-Perez, D. C. Palmer, Z. Yu, et al.
Toll-like Receptors in Tumor Immunotherapy
Clin. Cancer Res., September 15, 2007; 13(18): 5280 - 5289.
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M. R. Smith, F. Jin, and I. Joshi
Bortezomib Sensitizes Non Hodgkin's Lymphoma Cells to Apoptosis Induced by Antibodies to Tumor Necrosis Factor Related Apoptosis-Inducing Ligand (TRAIL) Receptors TRAIL-R1 and TRAIL-R2
Clin. Cancer Res., September 15, 2007; 13(18): 5528s - 5534s.
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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.
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E. Cooney-Qualter, M. Krailo, A. Angiolillo, R. A. Fawwaz, G. Wiseman, L. Harrison, V. Kohl, P. C. Adamson, J. Ayello, C. vande Ven, et al.
A Phase I Study of 90Yttrium-Ibritumomab-Tiuxetan in Children and Adolescents with Relapsed/Refractory CD20-Positive Non Hodgkin's Lymphoma: A Children's Oncology Group Study
Clin. Cancer Res., September 15, 2007; 13(18): 5652s - 5660s.
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C. E. Dearden
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Br. Med. Bull., September 1, 2007; 83(1): 275 - 290.
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Y. Tang, J. Lou, R. K. Alpaugh, M. K. Robinson, J. D. Marks, and L. M. Weiner
Regulation of Antibody-Dependent Cellular Cytotoxicity by IgG Intrinsic and Apparent Affinity for Target Antigen
J. Immunol., September 1, 2007; 179(5): 2815 - 2823.
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P. Cravedi, P. Ruggenenti, M. C. Sghirlanzoni, and G. Remuzzi
Titrating Rituximab to Circulating B Cells to Optimize Lymphocytolytic Therapy in Idiopathic Membranous Nephropathy
Clin. J. Am. Soc. Nephrol., September 1, 2007; 2(5): 932 - 937.
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F. Breedveld, S. Agarwal, M. Yin, S. Ren, N. F. Li, T. M. Shaw, and B. E. Davies
Rituximab Pharmacokinetics in Patients With Rheumatoid Arthritis: B-Cell Levels Do Not Correlate With Clinical Response
J. Clin. Pharmacol., September 1, 2007; 47(9): 1119 - 1128.
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L. Gerard, A. Berezne, L. Galicier, V. Meignin, M. Obadia, N. De Castro, C. Jacomet, R. Verdon, I. Madelaine-Chambrin, E. Boulanger, et al.
Prospective Study of Rituximab in Chemotherapy-Dependent Human Immunodeficiency Virus Associated Multicentric Castleman's Disease: ANRS 117 CastlemaB Trial
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K. Yanaba, Y. Hamaguchi, G. M. Venturi, D. A. Steeber, E. W. St. Clair, and T. F. Tedder
B Cell Depletion Delays Collagen-Induced Arthritis in Mice: Arthritis Induction Requires Synergy between Humoral and Cell-Mediated Immunity
J. Immunol., July 15, 2007; 179(2): 1369 - 1380.
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P. Sabbatini and K. Odunsi
Immunologic Approaches to Ovarian Cancer Treatment
J. Clin. Oncol., July 10, 2007; 25(20): 2884 - 2893.
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D. L. Reidy, K. Y. Chung, J. P. Timoney, V. J. Park, E. Hollywood, N. T. Sklarin, R. J. Muller, and L. B. Saltz
Bevacizumab 5 mg/kg Can Be Infused Safely Over 10 Minutes
J. Clin. Oncol., July 1, 2007; 25(19): 2691 - 2695.
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J. Leonard, J. Friedberg, A Younes, D Fisher, L. Gordon, J Moore, M Czuczman, T Miller, P Stiff, B. Cheson, et al.
A phase I/II study of galiximab (an anti-CD80 monoclonal antibody) in combination with rituximab for relapsed or refractory, follicular lymphoma
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J. M. Pagel, A. Pantelias, N. Hedin, S. Wilbur, L. Saganic, Y. Lin, D. Axworthy, D. K. Hamlin, D. S. Wilbur, A. K. Gopal, et al.
Evaluation of CD20, CD22, and HLA-DR Targeting for Radioimmunotherapy of B-Cell Lymphomas
Cancer Res., June 15, 2007; 67(12): 5921 - 5928.
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M. H.J. van Oers
Rituximab maintenance therapy: a step forward in follicular lymphoma
Haematologica, June 1, 2007; 92(6): 826 - 833.
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T. E. Witzig, D. J. Inwards, T. M. Habermann, A. Dogan, P. J. Kurtin, J. B. Gross Jr, A. Ananthamurthy, K. M. Ristow, and J. A. Garrity
Treatment of Benign Orbital Pseudolymphomas With the Monoclonal Anti-CD20 Antibody Rituximab
Mayo Clin. Proc., June 1, 2007; 82(6): 692 - 699.
[Abstract] [Full Text] [PDF]

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A. Pantelias, J. M. Pagel, N. Hedin, L. Saganic, S. Wilbur, D. K. Hamlin, D. S. Wilbur, Y. Lin, D. Stone, D. Axworthy, et al.
Comparative biodistributions of pretargeted radioimmunoconjugates targeting CD20, CD22, and DR molecules on human B-cell lymphomas
Blood, June 1, 2007; 109(11): 4980 - 4987.
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J. G. Gribben
How I treat indolent lymphoma
Blood, June 1, 2007; 109(11): 4617 - 4626.
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M. Herold, A. Haas, S. Srock, S. Neser, K. H. Al-Ali, A. Neubauer, G. Dolken, R. Naumann, W. Knauf, M. Freund, et al.
Rituximab Added to First-Line Mitoxantrone, Chlorambucil, and Prednisolone Chemotherapy Followed by Interferon Maintenance Prolongs Survival in Patients With Advanced Follicular Lymphoma: An East German Study Group Hematology and Oncology Study
J. Clin. Oncol., May 20, 2007; 25(15): 1986 - 1992.
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L. H. Sehn, J. Donaldson, A. Filewich, C. Fitzgerald, K. K. Gill, N. Runzer, B. Searle, S. Souliere, J. J. Spinelli, J. Sutherland, et al.
Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can safely be delivered in the community setting
Blood, May 15, 2007; 109(10): 4171 - 4173.
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H. Schulz, J. F. Bohlius, S. Trelle, N. Skoetz, M. Reiser, T. Kober, G. Schwarzer, M. Herold, M. Dreyling, M. Hallek, et al.
Immunochemotherapy With Rituximab and Overall Survival in Patients With Indolent or Mantle Cell Lymphoma: A Systematic Review and Meta-analysis
J Natl Cancer Inst, May 2, 2007; 99(9): 706 - 714.
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S. A. Hammond, R. Lutterbuese, S. Roff, P. Lutterbuese, B. Schlereth, E. Bruckheimer, M. S. Kinch, S. Coats, P. A. Baeuerle, P. Kufer, et al.
Selective Targeting and Potent Control of Tumor Growth Using an EphA2/CD3-Bispecific Single-Chain Antibody Construct
Cancer Res., April 15, 2007; 67(8): 3927 - 3935.
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S. Nomura, K. Ishii, Y. Kamitsuji, N. Uoshima, E. Ishikawa, H. Kitayama, and K. Hayashi
Elevation of Activated Platelet-Dependent Chemokines in Patients With Anti-CD20 Monoclonal Antibody (Rituximab)-Treated Non-Hodgkin's Lymphoma
Clinical and Applied Thrombosis/Hemostasis, April 1, 2007; 13(2): 206 - 212.
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H. Singh, L. M. Serrano, T. Pfeiffer, S. Olivares, G. McNamara, D. D. Smith, Z. Al-Kadhimi, S. J. Forman, S. D. Gillies, M. C. Jensen, et al.
Combining Adoptive Cellular and Immunocytokine Therapies to Improve Treatment of B-Lineage Malignancy
Cancer Res., March 15, 2007; 67(6): 2872 - 2880.
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 The OncologistHome page
J. Hayslip and R. Fenning
Safe Administration of Iodine-131 Tositumomab After Repeated Infusion-Related Reactions to Rituximab
Oncologist, March 1, 2007; 12(3): 338 - 340.
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A. Niedermeier, R. Eming, M. Pfutze, C. R. Neumann, C. Happel, K. Reich, and M. Hertl
Clinical Response of Severe Mechanobullous Epidermolysis Bullosa Acquisita to Combined Treatment With Immunoadsorption and Rituximab (Anti-CD20 Monoclonal Antibodies)
Arch Dermatol, February 1, 2007; 143(2): 192 - 198.
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E Nitta, K Izutsu, T Sato, Y Ota, K Takeuchi, A Kamijo, K Takahashi, K Oshima, Y Kanda, S Chiba, et al.
A high incidence of late-onset neutropenia following rituximab-containing chemotherapy as a primary treatment of CD20-positive B-cell lymphoma: a single-institution study
Ann. Onc., February 1, 2007; 18(2): 364 - 369.
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W. R. Sperr, K. Lechner, and I. Pabinger
Rituximab for the treatment of acquired antibodies to factor VIII
Haematologica, January 1, 2007; 92(1): 66 - 71.
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 ASH Education BookHome page
D. G. Maloney
Follicular NHL: From Antibodies and Vaccines to Graft-versus-Lymphoma Effects
Hematology, January 1, 2007; 2007(1): 226 - 232.
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C. Bello and E. M. Sotomayor
Monoclonal Antibodies for B-Cell Lymphomas: Rituximab and Beyond
Hematology, January 1, 2007; 2007(1): 233 - 242.
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 Rheumatology (Oxford)Home page
M. J. Leandro, N. Cooper, G. Cambridge, M. R. Ehrenstein, and J. C. W. Edwards
Bone marrow B-lineage cells in patients with rheumatoid arthritis following rituximab therapy
Rheumatology, January 1, 2007; 46(1): 29 - 36.
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 QJMHome page
C. Palmieri, T. Treibel, O. Large, and M. Bower
AIDS-related non-Hodgkin's lymphoma in the first decade of highly active antiretroviral therapy
QJM, December 1, 2006; 99(12): 811 - 826.
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K. D. Khan, C. Emmanouilides, D. M. Benson Jr., D. Hurst, P. Garcia, G. Michelson, S. Milan, A. K. Ferketich, L. Piro, J. P. Leonard, et al.
A Phase 2 Study of Rituximab in Combination with Recombinant Interleukin-2 for Rituximab-Refractory Indolent Non-Hodgkin's Lymphoma
Clin. Cancer Res., December 1, 2006; 12(23): 7046 - 7053.
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