Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab

Abstract

Radioimmunotherapy, targeting the CD20 antigen, in B-cell lymphoma has clearly demonstrated efficacy and tolerability over the preceding 15 years. As a result, two products are available with Food and Drug Administration approval for marketing – Y90 ibritumomab tiuxetan and I131 tositumomab, given as the Zevalin and Bexxar therapeutic regimens, respectively. Both demonstrate high-response rates and durability of remission in the relapsed/refractory disease setting. Data are emerging regarding their utility as initial therapy, and furthermore, they are been investigated for use sequentially with chemotherapy, and in the myeloablative setting. As yet however, how to best use these agents in the clinical disease course remains uncertain.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Andersen NS, Jensen MK, de Nully Brown P, Geisler CH . (2002). A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors. Eur J Cancer 38: 401–408.

    Article  CAS  PubMed  Google Scholar 

  • Anderson KC, Bates MP, Slaughenhoupt BL, Pinkus GS, Schlossman SF, Nadler LM . (1984). Expression of human B cell-associated antigens on leukemias and lymphomas: a model of human B cell differentiation. Blood 63: 1424–1433.

    CAS  PubMed  Google Scholar 

  • Ansell SM, Ristow KM, Habermann TM, Wiseman GA, Witzig TE . (2002). Subsequent chemotherapy regimens are well tolerated after radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for non-Hodgkin's lymphoma. J Clin Oncol 20: 3885–3890.

    Article  CAS  PubMed  Google Scholar 

  • Apostolidis J, Gupta RK, Grenzelias D, Johnson PW, Pappa VI, Summers KE et al (2000). High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow-up. J Clin Oncol 18: 527–536.

    Article  CAS  PubMed  Google Scholar 

  • Ardeshna KM, Smith P, Norton A, Hancock BW, Hoskin PJ, MacLennan KA et al. (2003). Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 362: 516–522.

    Article  CAS  PubMed  Google Scholar 

  • Armitage JO, Dick FR, Corder MP . (1981). Diffuse histiocytic lymphoma after histologic conversion: a poor prognostic variant. Cancer Treat Rep 65: 413–418.

    CAS  PubMed  Google Scholar 

  • Bartlett N, Witzig T, Gordon L, Beck T, Fehrenbacher L, Kornmehl E et al. (2002). 90Y-ibritumomab tiuxetan (Zevalin) radioimmunotherapy for transformed B-cell non-Hodgkin¦s lymphoma (NHL) patients. Proc Am Soc Clin Oncol 21: (abstr: 51).

  • Bastion Y, Sebban C, Berger F, Felman P, Salles G, Dumontet C et al. (1997). Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol 15: 1587–1594.

    Article  CAS  PubMed  Google Scholar 

  • Bennett JM, Kaminski MS, Leonard JP, Vose JM, Zelenetz AD, Knox SJ et al. (2005). Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab. Blood 105: 4576–4582.

    Article  CAS  PubMed  Google Scholar 

  • Buchsbaum DJ, Wahl RL, Glenn SD, Normolle DP, Kaminski MS . (1992a). Improved delivery of radiolabeled anti-B1 monoclonal antibody to Raji lymphoma xenografts by predosing with unlabeled anti-B1 monoclonal antibody. Cancer Res 52: 637–642.

    CAS  PubMed  Google Scholar 

  • Buchsbaum DJ, Wahl RL, Normolle DP, Kaminski MS . (1992b). Therapy with unlabeled and 131I-labeled pan-B-cell monoclonal antibodies in nude mice bearing Raji Burkitt's lymphoma xenografts. Cancer Res 52: 6476–6481.

    CAS  PubMed  Google Scholar 

  • Chatal JF, Harousseau JL, Griesinger JM, Meller J, Renner C, Kirsch CM et al. (2004). Radioimmunotherapy in non-Hodgkin's lymphoma (NHL) using a fractionated schedule of DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab. Proc Am Soc Clin Oncol 22: (Abstract 2545).

  • Cheson BD . (2003). Radioimmunotherapy of non-Hodgkin lymphomas. Blood 101: 391–398.

    Article  CAS  PubMed  Google Scholar 

  • Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R et al. (2002). CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346: 235–242.

    Article  CAS  PubMed  Google Scholar 

  • Connors JM . (2005). Radioimmunotherapy – hot new treatment for lymphoma. N Engl J Med 352: 496–498.

    Article  CAS  PubMed  Google Scholar 

  • Conti PS, White C, Pieslor P, Molina A, Aussie J, Foster P . (2005). The role of imaging with (111)In-ibritumomab tiuxetan in the ibritumomab tiuxetan (Zevalin) regimen: results from a Zevalin Imaging Registry. J Nucl Med 46: 1812–1818.

    CAS  PubMed  Google Scholar 

  • Cragg MS, Glennie MJ . (2004). Antibody specificity controls in vivo effector mechanisms of anti-CD20 reagents. Blood 103: 2738–2743.

    Article  CAS  PubMed  Google Scholar 

  • Cullen MH, Lister TA, Brearley RI, Shand WS, Stansfeld AG . (1979). Histological transformation of non-Hodgkin's lymphoma: a prospective study. Cancer 44: 645–651.

    Article  CAS  PubMed  Google Scholar 

  • Czuczman M, Witzig T, Gaston I, Skikne BS, Dimitrov G, Gordon L et al. (2002). Zevalin™ radioimmunotherapy is not associated with an increased incidence of secondary myelodysplastic syndrome or acute leukaemia. Blood 100: 357a (abstract 1386).

    Google Scholar 

  • Davies AJ, Howell S, Rohatiner AZ, Matthews J, Clayton J, Massey T et al. (2005). Long-term follow-up of patients recieving tositumomab and I31 tositumomab for recurrent and refractory B-cell lymphoma. Ann Oncol 16: v112 (abstract 256).

    Google Scholar 

  • Davies AJ, Rohatiner AZ, Howell S, Britton KE, Owens SE, Micallef IN et al. (2004). Tositumomab and iodine I 131 tositumomab for recurrent indolent and transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol 22: 1469–1479.

    Article  CAS  PubMed  Google Scholar 

  • Davis TA, Kaminski MS, Leonard JP, Hsu FJ, Wilkinson M, Zelenetz A et al. (2004). The radioisotope contributes significantly to the activity of radioimmunotherapy. Clin Cancer Res 10: 7792–7798.

    Article  CAS  PubMed  Google Scholar 

  • Dosik AD, Coleman M, Kostakoglu L, Furman RR, Fiore JM, Muss D et al. (2006). Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab for non-Hodgkin lymphoma. Cancer 106: 616–622.

    Article  CAS  PubMed  Google Scholar 

  • Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM et al. (2005). Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol 23: 7565–7573.

    Article  CAS  PubMed  Google Scholar 

  • Flinn IW, Kahl B, Frey EC, Bianco JA, Hammes RJ, Biling LS et al. (2004). Dose finding trial of Yttrium 90 (90Y) ibritumomab tiuxetan with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory B-Cell Non-Hodgkin's lymphoma (NHL). Blood 104: (abstract 897).

  • Forstpointner R, Unterhalt M, Dreyling M, Bock HP, Repp R, Wandt H et al. (2006). Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide and mitoxantrone (R-FCM) in patients with relapsed and refractory follicular and mantle cell lymphomas – results of a prospective randomized study of the German low grade lymphoma study group (GLSG). Blood 108: 4003–4008.

    Article  CAS  Google Scholar 

  • Fraker PJ, Speck Jr JC . (1978). Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun 80: 849–857.

    Article  CAS  PubMed  Google Scholar 

  • Freedman AS, Neuberg D, Mauch P, Soiffer RJ, Anderson KC, Fisher DC et al. (1999). Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 94: 3325–3333.

    CAS  PubMed  Google Scholar 

  • Fung H, Forman S, Nademanee A, Molina A, Yamauchi R, Speilberger N et al. (2003). A new preparative regimen for older patients with aggressive CD 20-positive B-cell lymphoma utilizing standard-dose Yttrium-90 ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) combined with high-dose BEAM followed by autologous hematopoietic cell transplantation (AHCT): targeted intensification without increased transplant-related toxicity. Blood 102: (Abstr act 870).

  • Gallagher CJ, Gregory WM, Jones AE, Stansfeld AG, Richards MA, Dhaliwal HS et al. (1986). Follicular lymphoma: prognostic factors for response and survival. J Clin Oncol 4: 1470–1480.

    Article  CAS  PubMed  Google Scholar 

  • Gopal AK, Gooley TA, Maloney DG, Petersdorf SH, Eary JF, Rajendran JG et al. (2003). High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: a multivariable cohort analysis. Blood 102: 2351–2357.

    Article  CAS  PubMed  Google Scholar 

  • Gopal AK, Pagel JM, Rajendran JG, Maloney DG, Appelbaum FR, Sorror ML et al. (2006). Improving the efficacy of reduced intensity allogeneic transplantation for lymphoma using radioimmunotherapy. Biol Blood Marrow Transplant 12: 697–702.

    Article  CAS  PubMed  Google Scholar 

  • Gopal AK, Rajendran JG, Petersdorf SH, Maloney DG, Eary JF, Wood BL et al. (2002). High-dose chemo-radioimmunotherapy with autologous stem cell support for relapsed mantle cell lymphoma. Blood 99: 3158–3162.

    Article  CAS  PubMed  Google Scholar 

  • Gordon L, Witzig T, Murray MS, Czuczman M, Emmanouilides C, Joyce RM et al. (2003). Yttrium-90 ibritumomab tiuxetan radioimmunotherapy produces high response rates and durable remissions in patients with relapsed or refractory low grade, follicular or transformed B-cell NHL: Final results of a randomized controlled trial. Proc Am Soc Clin Oncol 22: 576 (abstract 2315).

    Google Scholar 

  • Gordon LI, Molina A, Witzig T, Emmanouilides C, Raubtischek A, Darif M et al. (2004). Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1/2 study. Blood 103: 4429–4431.

    Article  CAS  PubMed  Google Scholar 

  • Gregory SA, Leonard J, Knox SJ, Zelenetz A, Armitage JO, Kaminski M . (2004). The iodine I-131 tositumomab therapeutic regimen: Summary of safety in 995 patients with relapsed/refractory low grade (LG) and transformed LG non-Hodgkin's lymphoma (NHL). Proc Am Soc Clin Oncol 22: 6732.

    Article  Google Scholar 

  • Gregory SA, Leonard J, Vose J, Zelenetz A, Horning S, Knox SJ et al. (2005). Superior outcomes associated with earlier use: experience with tositumomab and iodine I 131 tositumomab in 1,177 patients (pts) with low-grade, follicular, and transformed non-Hodgkin's lymphoma (NHL). Proc Am Soc Clin Oncol 23: 585 (Abstract 6561).

    Article  CAS  Google Scholar 

  • Gregory SA, Zelenetz A, Knox SJ, Vose J, Magnuson D, Kaminski M . (2001). The BEXXAR® therapeutic regimen (tositumomab and iodine I 131 tositumomab) can be safely administered to patients over the age of 70. Blood 102: 409a (abstract 1485).

    Google Scholar 

  • Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R et al. (2005). Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 106: 3725–3732.

    Article  CAS  PubMed  Google Scholar 

  • Horning SJ . (1993). Natural history of and therapy for the indolent non-Hodgkin's lymphomas. Semin Oncol 20: 75–88.

    CAS  PubMed  Google Scholar 

  • Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D et al. (2005). Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol 23: 712–719.

    Article  CAS  PubMed  Google Scholar 

  • Hubbard SM, Chabner BA, DeVita Jr VT, Simon R, Berard CW, Jones RB et al. (1982). Histologic progression in non-Hodgkin's lymphoma. Blood 59: 258–264.

    CAS  PubMed  Google Scholar 

  • Hunault-Berger M, Ifrah N, Solal-Celigny P . (2002). Intensive therapies in follicular non-Hodgkin lymphomas. Blood 100: 1141–1152.

    CAS  PubMed  Google Scholar 

  • Jacobs SA, Vidnovic N, Joyce J, McCook B, Torok F, Avril N . (2005). Full-dose 90Y ibritumomab tiuxetan therapy is safe in patients with prior myeloablative chemotherapy. Clin Cancer Res 11: 7146s–77150s.

    Article  CAS  PubMed  Google Scholar 

  • Johnson PW, Rohatiner AZ, Whelan JS, Price CG, Love S, Lim J et al. (1995). Patterns of survival in patients with recurrent follicular lymphoma: a 20-year study from a single center. J Clin Oncol 13: 140–147.

    Article  CAS  PubMed  Google Scholar 

  • Johnson TA, Press OW . (2000). Synergistic cytotoxicity of iodine-131-anti-CD20 monoclonal antibodies and chemotherapy for treatment of B-cell lymphomas. Int J Cancer 85: 104–112.

    Article  CAS  PubMed  Google Scholar 

  • Justice TE, Martenson JA, Wiseman GA, Witzig TE . (2006). Safety and efficacy of external beam radiation therapy for non-Hodgkin lymphoma in patients with prior 90Y-ibritumomab tiuxetan radioimmunotherapy. Cancer 107: 433–438.

    Article  CAS  PubMed  Google Scholar 

  • Kaminski M, Bahm V, Estes J, Ratanatharathorn V . (2001a). Tolerence of treatment sunbsequent to frontline Bexxar™ (tositumomab and I131 tositumomab) in patients with follicular lymphoma. Blood 98: (abstract 603a).

  • Kaminski M, Hamstra D, Estes J, Wahl RL . (2006). The impact of FLIPI on outcome of frontline treatment with single-agent I-131 tositumomab for follicular lymphoma. J Clin Oncol 24: (abstract 560a).

  • Kaminski M, Zelenetz A, Press O, Saleh M, Leonard J, Fehrenbacher L et al. (2004). Tositumomab and Iodine I 131 tositumomab (the BEXXAR® therapeutic regimen) produced ongoing, durable remissions of more than 5 years in 9 patients with Non-Hodgkin's lymphoma (NHL) in a pivotal study of patients refractory to their last chemotherapy. Blood 104: (abstract 2631).

  • Kaminski MS, Estes J, Zasadny KR, Francis IR, Ross CW, Tuck M et al. (2000). Radioimmunotherapy with iodine (131)I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood 96: 1259–1266.

    CAS  PubMed  Google Scholar 

  • Kaminski MS, Radford JA, Gregory SA, Leonard JP, Knox SJ, Kroll S et al. (2005a). Re-treatment with I-131 tositumomab in patients with non-Hodgkin's lymphoma who had previously responded to I-131 tositumomab. J Clin Oncol 23: 7985–7993.

    Article  CAS  PubMed  Google Scholar 

  • Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K et al. (2005b). 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 352: 441–449.

    Article  CAS  PubMed  Google Scholar 

  • Kaminski MS, Zasadny KR, Francis IR, Fenner MC, Ross CW, Milik AW et al. (1996). Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma. J Clin Oncol 14: 1974–1981.

    Article  CAS  PubMed  Google Scholar 

  • Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD et al. (1993). Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med 329: 459–465.

    Article  CAS  PubMed  Google Scholar 

  • Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher L et al. (2001b). Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol 19: 3918–3928.

    Article  CAS  PubMed  Google Scholar 

  • Knox SJ, Goris ML, Trisler K, Negrin R, Davis T, Liles TM et al. (1996). Yttrium-90-labeled anti-CD20 monoclonal antibody therapy of recurrent B-cell lymphoma. Clin Cancer Res 2: 457–470.

    CAS  PubMed  Google Scholar 

  • Leahy MF, Seymour JF, Hicks RJ, Turner JH . (2006). Multicenter phase II clinical study of iodine-131-rituximab radioimmunotherapy in relapsed or refractory indolent non-Hodgkin's lymphoma. J Clin Oncol 24: 4418–4425.

    Article  CAS  PubMed  Google Scholar 

  • Leonard J, Frenett G, Dillman RO, Gregory SA . (2001). Intermin saftey and effiacy results of Bexxar™ in a large multicenter expanded acess study. Blood 98: 133a (abstr.).

    Google Scholar 

  • Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR et al. (2005). Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol 23: 5696–5704.

    Article  CAS  PubMed  Google Scholar 

  • Link B, Kaminski M, Coleman M, Leonard J . (2004). Phase II study of CVP followed by tositumomab and iodine I 131 tositumomab (Bexxar therapeutic regimen) in patients with untreated follicular non-Hodgkin's lymphoma. J Clin Oncol 22: (Abstract 6520).

  • Liu SY, Eary JF, Petersdorf SH, Martin PJ, Maloney DG, Appelbaum FR et al. (1998). Follow-up of relapsed B-cell lymphoma patients treated with iodine-131-labeled anti-CD20 antibody and autologous stem-cell rescue. J Clin Oncol 16: 3270–3278.

    Article  CAS  PubMed  Google Scholar 

  • Mac Manus MP, Hoppe RT . (1996). Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J Clin Oncol 14: 1282–1290.

    Article  CAS  PubMed  Google Scholar 

  • Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J et al. (2005). CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 105: 1417–1423.

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin P, Grillo-Lopez AJ, Link BK, Levy R, Czuczman MS, Williams ME et al. (1998). Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16: 2825–2833.

    Article  CAS  PubMed  Google Scholar 

  • Mones J, Coleman M, Kostakoglu L, Fiore J, Muss D, Furman RR et al. (2004). A dose-escalation study of tositumomab and iodine I 131 tositumomab (Bexxar) in pts with previously treated non-Hodgkin's lymphoma (NHL) with >25% bone marrow involvement. Proc Am Soc Clin Oncol 22: (Abstract 6575).

  • Morschhauser, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Hadjiyiannakis D et al. (2004). Yttrium-90 ibritumomab tiuxetan (Zevalin) for patients with relapsed/refractory diffuse large B-cell lymphoma not appropriate for autologous stem cell transplantation: results of an open-label phase II trial. Blood 104: (Abstract 130).

  • Nademanee A, Forman S, Molina A, Fung H, Smith D, Dagis A et al. (2005). A phase 1/2 trial of high-dose yttrium-90-ibritumomab tiuxetan in combination with high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood 106: 2896–2902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nadler LM, Stashenko P, Hardy R, Kaplan WD, Button LN, Kufe DW et al. (1980). Serotherapy of a patient with a monoclonal antibody directed against a human lymphoma-associated antigen. Cancer Res 40: 3147–3154.

    CAS  PubMed  Google Scholar 

  • Oki Y, Pro B, Delpassand ES, Ballaster V, McLaughlin P, Romaguera J et al. (2004). A phase II study of yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin®) for treatment of patients with relapsed and refractory mantle cell lymphoma (MCL). Blood 104: (Abstract 2632).

  • Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K et al. (2006). CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol 7: 379–391.

    Article  CAS  PubMed  Google Scholar 

  • Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D et al. (1995). Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 333: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  • Press OW, Eary JF, Appelbaum FR, Martin PJ, Badger CC, Nelp WB et al. (1993). Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med 329: 1219–1224.

    Article  CAS  PubMed  Google Scholar 

  • Press OW, Eary JF, Appelbaum FR, Martin PJ, Nelp WB, Glenn S et al. (1995). Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet 346: 336–340.

    Article  CAS  PubMed  Google Scholar 

  • Press OW, Eary JF, Gooley T, Gopal AK, Liu S, Rajendran JG et al. (2000). A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas. Blood 96: 2934–2942.

    CAS  PubMed  Google Scholar 

  • Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, Leblanc M et al. (2006). Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin's lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911. J Clin Oncol 24: 4143–4149.

    Article  CAS  PubMed  Google Scholar 

  • Press OW, Unger JM, Braziel RM, Maloney DG, Miller TP, LeBlanc M et al. (2003). A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911. Blood 102: 1606–1612.

    Article  CAS  PubMed  Google Scholar 

  • Radford JA, Ketterer N, Sebban C, Zinzani PL, Delaloye AB, Rohatiner AZ et al. (2003). Ibritumomab tiuxetan (Zevalin) therapy is feasible and safe for the treatment of patients with advanced B-cell follicular NHL in first remission: interim analysis for safety of a multicenter, phase III clinical trial. Blood 102 (Abstract 1484).

  • Schilder R, Witzig T, Gordon L, Emmanouilides C, Bartlett N, Flinn IW et al. (2002). 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy does not preclude effective delivery of subsequent therapy for lymphoma Proc. Am Soc Clin Oncol 21: 267a (abtract 1065).

    Google Scholar 

  • Schouten HC, Qian W, Kvaloy S, Porcellini A, Hagberg H, Johnson HE et al. (2003). High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin's lymphoma: results from the randomized European CUP trial. J Clin Oncol 21: 3918–3927.

    Article  CAS  PubMed  Google Scholar 

  • Shah J, Harrough D, Savill W, Mueh J, Lister J, Jasthy S et al. (2006). Safety and efficacy of retreating follicular non-Hodgkin's lymphoma (NHL) with 90Y ibritumomab tiuxetan. J Clin Oncol 24 (Abstract 17528).

  • Shipley DL, Greco FA, Spigek DR, Edwards D, Mayfield M, Yost K et al. (2005). Rituximab with short duration chemotherapy followed by 90Y ibritumomab tiuxetan as first-line treatment for patients with follicular lymphoma: Update of a Minnie Pearl Cancer Research Network phase II trial. J Clin Oncol 23 (Abstract 6577).

  • Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M et al. (1999). International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive Non-Hodgkin's lymphomas: report of the jury. J Clin Oncol 17: 423–429.

    Article  CAS  PubMed  Google Scholar 

  • Siegel JA . (1998). Revised nuclear regulatory commission regulations for release of patients administered radioactive materials: outpatient iodine-131 anti-B1 therapy. J Nucl Med 39: 28S–33S.

    CAS  PubMed  Google Scholar 

  • Siegel JA, Kroll S, Regan D, Kaminski MS, Wahl RL . (2002). A practical methodology for patient release after tositumomab and (131)I-tositumomab therapy. J Nucl Med 43: 354–363.

    CAS  PubMed  Google Scholar 

  • Smith MR, Chen H, Gordon L, Foran JM, Kahl B, Advani R et al. (2006). Phase II study of rituximab+CHOP followed by 90Y-ibritumomab tiuxetan in patients with previously untreated mantle cell lymphoma: an Eastern Cooperative Oncology Group Study (E1499). J Clin Oncol 24 (Abstract 7503).

  • Stashenko P, Nadler LM, Hardy R, Schlossman SF . (1980). Characterization of a human B lymphocyte-specific antigen. J Immunol 125: 1678–1685.

    CAS  PubMed  Google Scholar 

  • Stern M, Herrmann R . (2005). Overview of monoclonal antibodies in cancer therapy: present and promise. Crit Rev Oncol Hematol 54: 11–29.

    Article  CAS  PubMed  Google Scholar 

  • Sweetenham JW, Dicke K, Arcaroli J, Kogel K, Rana TM, Rice LL . (2004). Efficacy and safety of yttrium 90 (90Y) ibritumomab Tiuxetan (Zevalin(R)) therapy with rituximab maintenance in patients with untreated low-grade follicular lymphoma. ASH Annual Meeting Abstracts 104: 2633.

    Google Scholar 

  • Tedder TF, Forsgren A, Boyd AW, Nadler LM, Schlossman SF . (1986). Antibodies reactive with the B1 molecule inhibit cell cycle progression but not activation of human B lymphocytes. Eur J Immunol 16: 881–887.

    Article  CAS  PubMed  Google Scholar 

  • The Non-Hodgkin's Lymphoma Classification Project (1997). A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood 89: 3909–3918.

    Google Scholar 

  • van Oers MH, Klasa R, Marcus RE, Wolf M, Kimby E, Gascoyne RD et al. (2006). Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin's lymphoma, both in patients with and without rituximab during induction: results of a prospective randomized phase III intergroup trial. Blood.

  • Vose J, Bierman PJ, Lynch JC, Bociek G, Multani P, Armitage JO . (2003). Phase I clinical trial of Zevalin (90Y-Ibritumomab) in patients with B-cell Non-Hodgkins lymphoma (NHL) with relapsed disease following high-dose chemotherapy and autologous stem cell transplantation (ASCT). Blood 102 (abstract 92).

  • Vose JM . (2004). Bexxar: novel radioimmunotherapy for the treatment of low-grade and transformed low-grade non-Hodgkin's lymphoma. Oncologist 9: 160–172.

    Article  CAS  PubMed  Google Scholar 

  • Vose JM, Anderson JR, Kessinger A, Bierman PJ, Coccia P, Reed EC et al. (1993). High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma. J Clin Oncol 11: 1846–1851.

    Article  CAS  PubMed  Google Scholar 

  • Vose JM, Bierman PJ, Enke C, Hankins J, Bociek G, Lynch JC et al. (2005). Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma. J Clin Oncol 23: 461–467.

    Article  CAS  PubMed  Google Scholar 

  • Vose JM, Wahl RL, Saleh M, Rohatiner AZ, Knox SJ, Radford JA et al. (2000). Multicenter phase II study of iodine-131 tositumomab for chemotherapy-relapsed/refractory low-grade and transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol 18: 1316–1323.

    Article  CAS  PubMed  Google Scholar 

  • Wahl RL . (2003). The clinical importance of dosimetry in radioimmunotherapy with tositumomab and iodine I 131 tositumomab. Semin Oncol 30: 31–38.

    Article  CAS  PubMed  Google Scholar 

  • Wahl RL, Zasadny KR, MacFarlane D, Francis IR, Ross CW, Estes J et al. (1998). Iodine-131 anti-B1 antibody for B-cell lymphoma: an update on the Michigan Phase I experience. J Nucl Med 39: 21S–27S.

    CAS  PubMed  Google Scholar 

  • Wiseman GA, Gordon LI, Multani PS, Witzig TE, Spies S, Bartlett NL et al. (2002a). Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 99: 4336–4342.

    Article  CAS  PubMed  Google Scholar 

  • Wiseman GA, Kornmehl E, Leigh B, Erwin WD, Podoloff DA, Spies S et al. (2003). Radiation dosimetry results and safety correlations from 90Y-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: combined data from 4 clinical trials. J Nucl Med 44: 465–474.

    CAS  PubMed  Google Scholar 

  • Wiseman GA, Leigh B, Erwin WD, Lamonica D, Kornmehl E, Spies SM et al. (2002b). Radiation dosimetry results for Zevalin radioimmunotherapy of rituximab-refractory non-Hodgkin lymphoma. Cancer 94: 1349–1357.

    Article  CAS  PubMed  Google Scholar 

  • Wiseman GA, Witzig TE . (2005). Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) induces long-term durable responses in patients with relapsed or refractory B-Cell non-Hodgkin's lymphoma. Cancer Biother Radiopharm 20: 185–188.

    Article  CAS  PubMed  Google Scholar 

  • Witzig T, Molina A, Gordon L, Emmanouilides C, Schilder R, Flinn IW et al. (2003a). Yttrium 90 ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) induces durable remissions in patients with relapsed or refractory B-cell Non-Hodgkins lymphoma (NHL): analysis of long-term responders. Blood 102 (abstract 1480).

  • Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN et al. (2002a). Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol 20: 3262–3269.

    Article  CAS  PubMed  Google Scholar 

  • Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R et al. (2002b). Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma. J Clin Oncol 20: 2453–2463.

    Article  CAS  PubMed  Google Scholar 

  • Witzig TE, White CA, Gordon LI, Wiseman GA, Emmanouilides C, Murray JL et al. (2003b). Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-hodgkin's lymphoma. J Clin Oncol 21: 1263–1270.

    Article  CAS  PubMed  Google Scholar 

  • Witzig TE, White CA, Wiseman GA, Gordon LI, Emmanouilides C, Raubitschek A et al. (1999). Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20(+) B-cell non-Hodgkin's lymphoma. J Clin Oncol 17: 3793–3803.

    Article  CAS  PubMed  Google Scholar 

  • Zelenetz A, Noy A, Pandit-Taskar N, Scordo M, Rijo I, Zhou JA et al. (2006). Sequential radioimmunotherapy with tositumomab/Iodine I131 tositumomab followed by CHOP for mantle cell lymphoma demonstrates RIT can induce molecular remissions. J Clin Oncol 24 (Abstract 7560).

  • Zelenetz A, Saleh M, Vose J, Younes A, Kaminski M . (2002). Patients with transformed low grade lymphoma attain durable responses following outpatient radioimmunotherapy wit tositumomaba and I131 tostitumomab (Bexxar). Blood 100: 357a (abstract).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A J Davies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Davies, A. Radioimmunotherapy for B-cell lymphoma: Y90 ibritumomab tiuxetan and I131 tositumomab. Oncogene 26, 3614–3628 (2007). https://doi.org/10.1038/sj.onc.1210378

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1210378

Keywords

This article is cited by

Search

Quick links