Does Rituximab Have a Place in Treating Classic Hodgkin Lymphoma?
First Online: 20 May 2010 DOI:
Cite this article as: Oki, Y. & Younes, A. Curr Hematol Malig Rep (2010) 5: 135. doi:10.1007/s11899-010-0052-z Abstract
Monoclonal antibodies targeting surface proteins on the malignant Hodgkin and Reed-Sternberg (HRS) cells are currently under intensive investigation with promising early results. Of particular interest is the CD20 antigen, because it is expressed not only on a small fraction of HRS cells but also on the benign reactive B cells in the microenvironment. The rationale of using rituximab in classic Hodgkin lymphoma (cHL) comprises several points: 1) HRS cells infrequently express CD20; 2) elimination of CD20-positive reactive B cells supporting HRS cells would deprive the malignant cells of survival signals; 3) elimination of reactive B cells may also potentially increase host immune response against HRS cells; 4) HRS stem cells express CD20. Although this rationale has not generally been confirmed in patients, promising results in managing cHL have occurred in early-phase clinical trials of rituximab, including trials of rituximab as a single agent in refractory or recurrent cHL, rituximab plus gemcitabine in refractory or recurrent cHL, and rituximab plus ABVD in newly diagnosed cHL. Based on the results of these trials, several prospective clinical trials using rituximab in the management of advanced-stage cHL and early-stage cHL are ongoing. These trials further clarify the role of rituximab in cHL. Enrollment of patients with this “classic” disease in clinical trials is encouraged.
Keywords Classic Hodgkin lymphoma CD20 Rituximab Monoclonal antibody Immunotherapy References Papers of particular interest, published recently, have been highlighted as: •• Of major importance
Canellos GP, Anderson JR, Propert KJ, et al.: Chemotherapy of advanced Hodgkin’s disease with MOPP, ABVD, or MOPP alternating with ABVD. N Engl J Med 1992, 327:1478–1484.
Diehl V, Franklin J, Pfreundschuh M, et al.: Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin’s disease. N Engl J Med 2003, 348:2386–2395.
Hasenclever D, Diehl V: A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on Advanced Hodgkin’s Disease. N Engl J Med 1998, 339:1506–1514.
Rassidakis GZ, Medeiros LJ, Viviani S, et al.: CD20 expression in Hodgkin and Reed-Sternberg cells of classical Hodgkin’s disease: associations with presenting features and clinical outcome. J Clin Oncol 2002, 20:1278–1287.
•• Jones RJ, Gocke CD, Kasamon YL, et al.: Circulating clonotypic B cells in classic Hodgkin lymphoma. Blood 2009, 113:5920–5926.
This study illustrates the characteristics of Hodgkin lymphoma stem cells
Inoue S, Leitner WW, Golding B, Scott D: Inhibitory effects of B cells on antitumor immunity. Cancer Res 2006, 66:7741–7747.
Ekstrand BC, Lucas JB, Horwitz SM, et al.: Rituximab in lymphocyte-predominant Hodgkin disease: results of a phase 2 trial. Blood 2003, 101:4285–4289.
Schulz H, Rehwald U, Morschhauser F, et al.: Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG). Blood 2008, 111:109–111.
Younes A, Romaguera J, Hagemeister F, et al.: A pilot study of rituximab in patients with recurrent, classic Hodgkin disease. Cancer 2003, 98:310–314.
Oki Y, Younes A: Current role of gemcitabine in the treatment of Hodgkin lymphoma. Leuk Lymphoma 2008, 49:883–889.
Oki Y, Pro B, Fayad LE, et al.: Phase 2 study of gemcitabine in combination with rituximab in patients with recurrent or refractory Hodgkin lymphoma. Cancer 2008, 112:831–836
Corazzelli G, Frigeri F, Marcacci G, et al.: Rituximab plus gemcitabine, ifosfamide, oxaliplatin (R-GIFOX) as salvage therapy for recurrent Hodgkin lymphoma [abstract]. J Clin Oncol 2009; 27:Abstract 8579.
•• Copeland AR, Cao Y, Fanale M, et al.: Final report of a phase-II study of rituximab plus ABVD for patients with newly diagnosed advanced stage classical Hodgkin lymphoma: Results of long follow-up and comparison to institutional historical data [abstract]. Blood (ASH Annual Meeting Abstracts) 2009, 114:1680a.
This study showed the clinical benefit of using rituximab in the management of classic HL; it serves as the rationale for currently ongoing clinical trials.
Tepler I, Schwartz G, Parker K, et al.: Phase I trial of an interleukin-2 fusion toxin (DAB486IL-2) in hematologic malignancies: complete response in a patient with Hodgkin’s disease refractory to chemotherapy. Cancer 1994, 73:1276–1285.
LeMaistre CF, Saleh MN, Kuzel TM, et al.: Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-2. Blood 1998, 91:399–405.
Kreitman RJ, Wilson WH, White JD, et al.: Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol 2000, 18:1622–1636.
Bartlett NL, Younes A, Carabasi MH, et al.: A phase 1 multidose study of SGN-30 immunotherapy in patients with refractory or recurrent CD30+ hematologic malignancies. Blood 2008, 111:1848–1854.
Ansell SM, Horwitz SM, Engert A, et al.: Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin’s lymphoma and anaplastic large-cell lymphoma. J Clin Oncol 2007, 25:2764–2769.
Hartmann F, Renner C, Jung W, et al.: Anti-CD16/CD30 bispecific antibody treatment for Hodgkin’s disease: role of infusion schedule and costimulation with cytokines. Clin Cancer Res 2001, 7:1873–1881.
Schnell R, Dietlein M, Staak JO, et al.: Treatment of refractory Hodgkin’s lymphoma patients with an iodine-131-labeled murine anti-CD30 monoclonal antibody. J Clin Oncol 2005, 23:4669–4678.
Younes A, Forero-Torres A, Bartlett NL, et al.: Multiple complete responses in a phase 1 dose-escalation study of the antibody-drug conjugate SGN-35 in patients with relapsed or refractory CD30-positive lymphomas [abstract]. Blood (ASH Annual Meeting Abstracts) 2008, 112:1006a.
Study of HCD122 in adults with non-Hodgkin’s or Hodgkin’s lymphoma who have progressed after at least two prior therapies [NCT00670592]. Available at
Galiximab in treating patients with relapsed or refractory Hodgkin’s lymphoma [NCT00516217]. Available at
Decaudin D, Levy R, Lokiec F, et al.: Radioimmunotherapy (RIT) of refractory or relapsed Hodgkin’s lymphoma (HL) with 90Yttrium-labelled antiferritin antibody [abstract]. Blood (ASH Annual Meeting Abstracts) 2007, 110:4473a.
Herpst JM, Klein JL, Leichner PK, et al.: Survival of patients with resistant Hodgkin’s disease after polyclonal yttrium 90-labeled antiferritin treatment. J Clin Oncol 1995, 13:2394–2400.
Vriesendorp HM, Quadri SM, Wyllie CT, et al.: Fractionated radiolabeled antiferritin therapy for patients with recurrent Hodgkin’s disease. Clin Cancer Res 1999, 5:3324s–3329s.
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