Skip to main content
SpringerLink
Log in

Radioimmunotherapy: Strategies for the future in indolent and aggressive lymphoma

  • Published:
Current Oncology Reports Aims and scope Submit manuscript

Abstract

The conjugation of radioisotopes to monoclonal antibodies, or radioimmunotherapy (RIT), is a highly active treatment in non-Hodgkin’s lymphoma. RIT has demonstrated high response rates and durable remissions in extensively pretreated patients and has proved highly effective as consolidation after induction chemotherapy in the first-line therapy of follicular lymphoma. Earlyphase clinical trials have shown highly promising results using RIT as part of conditioning regimens in patients who are to undergo transplantation and as consolidation after chemotherapy in patients with aggressive lymphomas. Recent data suggest that integrating RIT with immunochemotherapy and transplant conditioning regimens may further improve outcomes for patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Green MR: Targeting targeted therapy. N Engl J Med 2004, 350:2191–2193.

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  3. Coiffier B, Lepage E, Briere J, et al.: CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002, 346:235–242.

    Article  PubMed  CAS  Google Scholar 

  4. Schulz H, Bohlius JF, Trelle S, 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 2007, 99:706–714.

    Article  PubMed  CAS  Google Scholar 

  5. Horning SJ, Rosenberg SA: The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med 1984, 311:1471–1475.

    PubMed  CAS  Google Scholar 

  6. Knox SJ, Meredith RF: Clinical radioimmunotherapy. Semin Radiat Oncol 2000, 10:73–93.

    Article  PubMed  CAS  Google Scholar 

  7. Illidge TM, Johnson PWM: The emerging role of radioimmunotherapy in haematological malignancies. Br J Haematol 2000, 108:679–688.

    Article  PubMed  CAS  Google Scholar 

  8. Deacon J, Peckham MJ, Steel GG: The radioresponsiveness of human tumours and the initial slope of the cell survival curve. Radiother Oncol 1984, 2:317–323.

    Article  PubMed  CAS  Google Scholar 

  9. Press OW: Radiolabeled antibody therapy of B-cell lymphomas. Semin Oncol 1999, 5(Suppl 14):58–65.

    Google Scholar 

  10. Haas RLM, Poortmans P, de Jong D, et al.: High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. J Clin Oncol 2003, 21:2474–2480.

    Article  PubMed  CAS  Google Scholar 

  11. Mac Manus MP, Hoppe RT: 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 1996, 14:1282–1290.

    PubMed  CAS  Google Scholar 

  12. Witzig TE, Flinn IW, Gordon LI, et al.: Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol 2002, 20:3262–3269.

    Article  PubMed  CAS  Google Scholar 

  13. Witzig TE, White CA, Gordon LI, et al.: 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 2002, 20:2453–2463.

    Article  PubMed  CAS  Google Scholar 

  14. Kaminski MS, Zelenetz AD, Press OW, et al.: Pivotal study of iodine I 131 tositumomab for chemotherapyrefractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol 2001, 19:3918–3928.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  16. Emmanouilides C, Witzig TE, Gordon LI, et al.: Treatment with yttrium 90 ibritumomab tiuxetan at early relapse is safe and effective in patients with previously treated B-cell non-Hodgkin’s lymphoma. Leuk Lymphoma 2006, 47:629–636.

    Article  PubMed  CAS  Google Scholar 

  17. Kaminski MS, Tuck M, Estes J, et al.: 131I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 2005, 352:441–449.

    Article  PubMed  CAS  Google Scholar 

  18. Leonard JP, Coleman M, Kostakoglu L, et al.: Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol 2005, 23:5696–5704.

    Article  PubMed  CAS  Google Scholar 

  19. Press OW, Unger JM, Braziel RM, et al.: 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 2003, 102:1606–1612.

    Article  PubMed  CAS  Google Scholar 

  20. Link B, Kaminski MS, Coleman M, Leonard JP: 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 (NHL) [abstract]. J Clin Oncol 2004, 22(14 Suppl):6520.

    Google Scholar 

  21. Morschhauser F, Radford J, Van Hoof A, et al.: Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol 2008, 26:5156–5164.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  23. Fisher RI, Kaminski MS, Wahl RL, et al.: 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 2005, 23:7565–7573.

    Article  PubMed  CAS  Google Scholar 

  24. Witzig TE, White CA, Wiseman GA, et al.: Phase I/II trial of IDEC-Y2B8 radioimmunotherapy for treatment of relapsed or refractory CD20+ B-cell non-Hodgkin’s lymphoma. J Clin Oncol 1999, 17:3793–3803.

    PubMed  CAS  Google Scholar 

  25. Witzig TE, White CA, Gordon LI, et al.: Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin’s lymphoma. J Clin Oncol 2003, 21:1263–1270.

    Article  PubMed  CAS  Google Scholar 

  26. Emmanouilides C, Witzig TE, Wiseman GA, et al.: Safety and efficacy of yttrium-90 ibritumomab tiuxetan in older patients with non-Hodgkin’s lymphoma. Cancer Biother Radiopharm 2007, 22:684–691.

    Article  PubMed  CAS  Google Scholar 

  27. Morschhauser F, Illidge T, Huglo D, et al.: Efficacy and safety of yttrium-90 ibritumomab tiuxetan in patients with relapsed or refractory diffuse large B-cell lymphoma not appropriate for autologous stem-cell transplantation. Blood 2007, 110:54–58.

    Article  PubMed  CAS  Google Scholar 

  28. Younes A, Pro B, Rodriguez MA, et al.: Activity of yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin) in 22 patients with relapsed and refractory mantle cell lymphoma (MCL) [abstract]. ASH Annual Meeting Abstracts 2005, 106:2452.

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  31. Krishnan A, Nademanee A, Fung HC, et al.: Phase II trial of a transplantation regimen of yttrium-90 ibritumomab tiuxetan and high-dose chemotherapy in patients with non-Hodgkin’s lymphoma. J Clin Oncol 2008, 26:90–95.

    Article  PubMed  CAS  Google Scholar 

  32. Winter JN, Inwards DJ, Spies S, et al.: Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2009, 27:1653–1659.

    Article  PubMed  CAS  Google Scholar 

  33. Shipley DL, Greco FA, Spigel DR, et al.: 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 [abstract]. J Clin Oncol 2005, 23(16 Suppl):6577.

    Google Scholar 

  34. Jacobs SA, Swerdlow SH, Kant J, et al.: Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Clin Cancer Res 2008, 14:7088–7094.

    Article  PubMed  CAS  Google Scholar 

  35. Sharkey RM, Press OW, Goldenberg DM: A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy. Blood 2009, 113:3891–3895.

    Article  PubMed  CAS  Google Scholar 

  36. Gopal AK, Press OW, Wilbur SM, et al.: Rituximab blocks binding of radiolabeled anti-CD20 antibodies (Ab) but not radiolabeled anti-CD45 Ab. Blood 2008, 112:830–835.

    Article  PubMed  CAS  Google Scholar 

  37. Illidge TM, Bayne M, Brown NS, et al.: Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy. Blood 2009, 113:1412–1421.

    Article  PubMed  CAS  Google Scholar 

  38. Tobinai K, Watanabe T, Ogura M, et al.: Japanese phase II study of 90Y-ibritumomab tiuxetan in patients with relapsed or refractory indolent B-cell lymphoma. Cancer Sci 2009, 100:158–164.

    Article  PubMed  CAS  Google Scholar 

  39. Jurczak W, Giza A, Szostek M, et al.: 90Y-Zevalin(R) (90Y-ibritumomab tiuxetan) radioimmunotherapy (RIT) consolidation of FCM induction chemotherapy in mantle cell lymphoma (MCL) patients: results from the PLRG upon completed enrollment [abstract]. ASH Annual Meeting Abstracts 2006, 108:2747.

    Google Scholar 

  40. Smith MR, Chen H, Gordon L, et al.: 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) [abstract]. J Clin Oncol (Meeting Abstracts) 2006, 24:7503.

    Google Scholar 

  41. van Oers MHJ, Klasa R, Marcus RE, et al.: Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood 2006, 108:3295–3301.

    Article  PubMed  Google Scholar 

  42. Hamlin PA, Moskowitz CH, Wegner BC, et al.: Early safety and efficacy analysis of a phase II study of sequential RCHOP and yttrium-90 ibritumomab tiuxetan (Zevalin) for elderly high risk patients with untreated DLBCL [abstract]. ASH Annual Meeting Abstracts 2005, 106:926.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Cancer and Imaging Sciences, Paterson Institute for Cancer Research, University of Manchester, Manchester, M20 4BX, UK

    Tim M. Illidge

Authors
  1. Waleed Alduaij
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tim M. Illidge
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tim M. Illidge.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Alduaij, W., Illidge, T.M. Radioimmunotherapy: Strategies for the future in indolent and aggressive lymphoma. Curr Oncol Rep 11, 363–370 (2009). https://doi.org/10.1007/s11912-009-0049-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11912-009-0049-8

Keywords

Search

Navigation