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Radioimmunotherapy of Lymphoma

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Abstract

Lymphoma is a generic term describing a malignant tumor originating in lymphoid tissue. In the United States, Western Europe, and other developed countries, it is the most common hematologic malignancy. At the present time, lymphomas, both Hodgkin’s and non-Hodgkin’s, represent 5–6 % of all malignant tumors (excluding superficial skin cancers) in these countries. In 2008, there were approximately 450,000 men and women living in the United States who had had the diagnosis of non-Hodgkin’s lymphoma (NHL); 55 % were men. In 2011, it is estimated that 66,000 new cases of NHL were diagnosed in the United States. NHL can occur at any age but the vast majority (almost 90 %) of cases will be diagnosed after age 50. Hodgkin’s lymphoma can also occur at any age, but it is more common in a younger age group (<30 years old). Consequently, the median age at diagnosis of NHL is 66 years of age with a median survival of 9 years. Many patients respond well to a variety of treatments and in some cases will be cured of the disease. Nevertheless, in 2011, over 19,000 patients in the United States died of the disease [1].

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References

  1. Cancer statistics, NHL SEER Fact Sheets. National Cancer Institute, 2012, USNIH. www.cancer.gov.

  2. Shipp MA, Mauch PM, Harris NL. Non-Hodgkin’s lymphomas. In: DeVita VT, Hellman S, Rosenberg SA, editors. Cancer, principles and practice of oncology. 5th ed. Philadelphia: Lippincott-Raven; 1997. p. 2165–219.

    Google Scholar 

  3. Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman Jr CA, Miller TP. Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin’s lymphoma. N Engl J Med. 1993;328:1002–6.

    Article  PubMed  CAS  Google Scholar 

  4. Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. 1975;256:495–7.

    Article  PubMed  CAS  Google Scholar 

  5. Davis TA, Grillo-López AJ, White CA, et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin’s lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000;18:3135–43.

    PubMed  CAS  Google Scholar 

  6. O’Donoghue JA, Bardies M, Wheldon TE. Relationships between tumor size and curability for uniformly targeted therapy with beta-emitting radionuclides. J Nucl Med. 1995;36:1902–9.

    PubMed  Google Scholar 

  7. Leonard JP, Siegel JA, Goldsmith SJ. Comparative physical and pharmacologic characteristics of iodine-131 and yttrium-90: implications for radioimmunotherapy for patients with non-Hodgkin’s lymphoma. Cancer Invest. 2003;21:241–52.

    Article  PubMed  CAS  Google Scholar 

  8. Goldsmith SJ. Radioimmunotherapy of lymphoma: Bexxar and Zevalin. Semin Nucl Med. 2010;40:122–35.

    Article  PubMed  Google Scholar 

  9. Press OW, Eary JF, Appelbaum FR, Martin PJ, Badger CC, Nelp WB, Glenn S, Butchko G, Fisher D, Porter B, Matthews DC, Fisher LD, Bernstein ID. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med. 1993;329:1219–24.

    Article  PubMed  CAS  Google Scholar 

  10. DeNardo GL, DeNardo SJ. Treatment of B-lymphocyte malignancies with 131I-Lym-1 and 67Cu-2IT-BAT-Lym-1 and opportunities for improvement. In: Goldenberg DM, editor. Cancer therapy with radiolabeled antibodies. Boca Raton: CRC; 1995. p. 217–27.

    Google Scholar 

  11. Kaminski MS, Fig LM, Zasadny KR, Koral KF, DelRosario RB, Francis IR, Hanson CA, Normolle DP, Mudgett E, Liu CP. Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma. J Clin Oncol. 1992;10:1696–711.

    PubMed  CAS  Google Scholar 

  12. Kaminski MS, Zasadny KR, Francis IR, Milik AW, Ross CW, Moon SD, Crawford SM, Burgess JM, Petry NA, Butchko GM, Glenn SD, Wahl RL. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med. 1993;329:459–65.

    Article  PubMed  CAS  Google Scholar 

  13. Kaminski MS, Zelenetz AD, Press OW, Saleh M, Leonard J, Fehrenbacher LT, Lister A, Stagg RJ, Tidmarsh GF, Kroll S, Wahl RL, Knox SJ, Vose JM. 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. 2001;93:3918–28.

    Google Scholar 

  14. Wahl RL. Tositumomab and 131I therapy in non-­Hodgkin’s lymphoma. J Nucl Med. 2002;46:128S–40.

    Google Scholar 

  15. Fisher RI, Kaminski MS, Wahl RL, Knox SJ, Zelenetz AD, Vose JM, Leonard JP, Kroll S, Goldsmith SJ, Coleman M. 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;23:7565–73.

    Article  PubMed  CAS  Google Scholar 

  16. Horning SJ, Younes A, Jain V, Kroll S, Lucas J, Podoloff D, Goris M. Efficacy and safety of tositumomab and iodine-131 tositumomab (bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005;23:712–9.

    Article  PubMed  CAS  Google Scholar 

  17. Leonard JP, Coleman M, Kostakoglu L, Chadburn A, Cesarman E, Furman RR, Schuster MW, Niesvitsky R, Muss D, Fiore J, Kroll S, Tidmarsh G, Vallabhajosula S, Goldsmith SJ. Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I-131 tositumomab for untreated follicular lymphoma. J Clin Oncol. 2005;23:5696–704.

    Article  PubMed  CAS  Google Scholar 

  18. Kaminski MS, Tuck M, Estes J, Kolstad A, Ross CW, Zasadny K, Regan D, Kison P, Fisher S, Kroll S, Wahl RL. 131I-tositumomabtherapy as initial treatment for follicular lymphoma. N Eng J Med. 2005;352:441–9.

    Article  CAS  Google Scholar 

  19. Link BK, Martin P, Kaminski MS, Goldsmith SJ, Coleman M, Leonard JP. Cyclophosphomide, vincristine and prednisone followed by tositumomab and I-131 tositumomab in patients with untreated low-grade follicular lymphoma: eight year follow-up of a multicenter phase II trial. J Clin Oncol. 2010;28:3035–41.

    Article  PubMed  CAS  Google Scholar 

  20. Dosik AD, Coleman M, Kostakoglu L, Furman RR, Fiore JM, Muss D, Niesvizky R, Shore T, Schister MW, Stewart P, Vallabhajosula S, Goldsmith SJ, Leonard JP. Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab for non-Hodgkin’s lymphoma. Cancer. 2006;106:616–22.

    Article  PubMed  CAS  Google Scholar 

  21. Witzig TE. Yttrium-90-ibritumomab tiuxetan radioimmunotherapy: a new treatment approach for B-cell non-Hodgkin’s lymphoma. Drugs Today (Barc). 2004;40:111–9.

    Article  CAS  Google Scholar 

  22. Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez A, Multani P, White CA. 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;20:2453–63.

    Article  PubMed  CAS  Google Scholar 

  23. Witzig TE, Flinn IW, Gordon LI, Emmanouilides C, Czuczman MS, Saleh MN, Cripe L, Wiseman GA, Olejnik T, Multani PS, White CA. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol. 2002;20:3262–9.

    Article  PubMed  CAS  Google Scholar 

  24. Emmanouilides C, Witzig TE, Gordon LI, Vo K, Wiseman GA, Flinn IW, Darif M, Schilder RJ, Molina A. 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;47:629–36.

    Article  PubMed  CAS  Google Scholar 

  25. Ansell SM, Schilder RJ, Pieslor PC, Gordon LI, Emmanouilides C, Vo K, Czuczman MS, Witzig TE, Theuer C, Molina A. Antilymphoma treatments given subsequent to Yttrium 90 ibritumomab tiuxetan are feasible in patients with progressive non-Hodgkin’s lymphoma: a review of the literature. Clin Lymphoma. 2004;5:202–4.

    Article  PubMed  Google Scholar 

  26. Morschhauser F, Radford J, Van Hoof A, Vitolo U, Soubeyran P, Tilly H, Huijgens PC, Kolstad A, d’Amore F, Gonzalez Diaz M, Petrini M, Sebban C, Zinzani PL, van Oers MH, van Putten W, Bischof-Delaloye A, Rohatiner A, Salles G, Kuhlmann J, Hagenbeek A. 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;26:5156–64.

    Article  PubMed  CAS  Google Scholar 

  27. Schaefer NG, Ma J, Huang P, Buchanan J, Wahl RL. Radioimmunotherapy in non-Hodgkin lymphoma: opinions of U.S. Medical Oncologists and Hematologists. J Nucl Med. 2010;51:987–94.

    Article  PubMed  Google Scholar 

  28. Schaefer NG, Huang P, Buchanan JW, Wahl RL. Radioimmunotherapy in non-Hodgkin lymphoma: opinions of nuclear medicine physicians and radiation oncologists. J Nucl Med. 2011;52:830–8.

    Article  PubMed  Google Scholar 

  29. Jacene HA, Filice R, Kasecamp W, Wahl RL. Comparison of 90Y-ibritumomab tiuxetan and 131I-tositumomab in clinical practice. J Nucl Med. 2007;48:1767–76.

    Article  PubMed  CAS  Google Scholar 

  30. Sharkey RM, Brenner A, Burton J, et al. Radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response? J Nucl Med. 2003;44:2000–18.

    PubMed  CAS  Google Scholar 

  31. Rutar FJ, Augustine SC, Colcher D, Siegel JA, Jacobson DA, Tempero MA, Dukat VJ, Hohenstein MA, Gobar LS, Vose JM. Outpatient treatment with 131I-anti-B1 antibody: radiation exposure to family members. J Nucl Med. 2001;42:907–15.

    PubMed  CAS  Google Scholar 

  32. Harwood SJ, Rutar F, Sullivan G, Avlonitis V. Bexxar radioimmunotherapy can be safely administered by healthcare professionals with minimal whole body exposure. J Nucl Med. 2003;44:327P.

    Google Scholar 

  33. Wagner HN, Wiseman GA, Marcus CS, Nabi HA, Nagle CE, Fink-Bennett DM, Lamonica DM, Conti PS. Administration guidelines for radioimmunotherapy with 90Y-labled anti-CD20 monoclonal antibody. J Nucl Med. 2002;43:267–72.

    PubMed  CAS  Google Scholar 

  34. Leahy MF, Seymour JF, Hicks RJ, Turner JH. Multicenter phase II clinical study of iodine-131–rituximab radioimmunotherapy in relapsed or refractory indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2006;24:4418–25.

    Article  PubMed  CAS  Google Scholar 

  35. Leonard JP, Coleman M, Matthews JC, et al. Phase I/II trial of Epratuzumab (humanized anti-CD 22 antibody) in indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2003;21:3051–9.

    Article  PubMed  CAS  Google Scholar 

  36. Linden O, Hindorf C, Cavallin-Stahl E, Wegener WA, Golenberg DM, Horne H, et al. Dose-fractionated radioimmmunotherapy in non-Hodgkin’s lymphoma using DOTA-conjugated, 90Y-radiolabeled humanized anti-CD22 monoclonal antibody, Epratuzumab. Clin Cancer Res. 2005;11:5215–22.

    Article  PubMed  CAS  Google Scholar 

  37. Morschhauser F, Kraeber-Bodere F, Wegener WA, Harousseau J-L, Petillon M-O, Huglo D, Trumper L, Meller J, Pfreundschuh M, Kirsch CM, Naumann R, Kropp J, Horne H, Teoh N, Le Gouill S, Bodet-Milin C, Chatal J-F, Goldenberg DM. High rates of durable responses with anti-CD22 fractionated radioimmunotherapy: results of a multicenter. Phase I/II study in non-Hodgkin’s lymphoma. J Clin Oncol. 2010;28:3709–16.

    Article  PubMed  CAS  Google Scholar 

  38. Sharkey RM, Press OW, Goldenberg DM. A re-examination of radioimmunotherapy in the treatment of non-Hodgkin’s lymphoma: prospects for dual-targeted antibody/radioantibody therapy. Blood. 2009;113:3891–5.

    Article  PubMed  CAS  Google Scholar 

  39. Press OW, Eary JF, Appelbaim FR, Bernstein ID. Treatment of relapsed B cell lymphoma with high dose radioimmunotherapy and bone marrow transplantation. In: Goldenberg DM, editor. Cancer therapy with radiolabeled antibodies. Boca Raton: CRC; 1995. p. 229–37.

    Google Scholar 

  40. Liu SY, Eary JF, Petersdorf SH, Martin PJ, Maloney DG, Appelbaum FR, Matthews DC, Bush SA, Durack LD, Fisher DR, Gooley TA, Bernstein ID, Press OW. 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;16:3270–8.

    PubMed  CAS  Google Scholar 

  41. Rajendran JG, Gopal AK, Fisher DR, Durack LD, Gooley TA, Press OW. Myeloablative 131I-tositumomab radioimmunotherapy in treating non-Hodgkin’s lymphoma: comparison of dosimetry based on whole-body retention and dose to critical organ receiving the highest dose. J Nucl Med. 2008;49:837–44.

    Article  PubMed  Google Scholar 

  42. Nademanee A, Forman S, Molina A, Fung H, Smith D, et al. A phase ½ trial of high-dose etoposide and cyclophosphamide followed by autologous stem cell transplantation in patients with poor-risk or relapsed non-Hodgkin lymphoma. Blood. 2005;106:2896–902.

    Article  PubMed  CAS  Google Scholar 

  43. Arico D, Grana CM, Vanazzi A, Ferrari M, Mallia A, Sansovini M, Martinelli G, Paganelli G, Cremonesi M. The role of dosimetry in the high activity 90Y-ibritumomab tiuxetan regimens: two cases of abnormal biodistribution. Cancer Biother Radiopharm. 2009;24:271–5.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The author expresses gratitude and appreciation to the staff of the Division of Nuclear Medicine & Molecular Imaging in the Department of Radiology at the New York Presbyterian Hospital/Weill Cornell Medical Center for their support and assistance in the clinical investigations and clinical practice of radioimmunotherapy of non-Hodgkin’s Lymphoma. In particular, I am grateful to Morton Coleman, MD, Shankar Vallabhajosula, PhD, John Leonard, MD, and Vasilios Avlonitis, RPh, for their support during the period in which we worked together to understand and improve the principles and practice of radioimmunotherapy and to make this therapy available to patients with non-­Hodgkin’s lymphoma.

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Authors and Affiliations

  1. Division of Nuclear Medicine and Molecular Imaging, New York-Presbyterian Hospital, Weill College of Medicine of Cornell University, 525 East 68th Street, New York, NY, 10065, USA

    Stanley J. Goldsmith M.D.

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  1. Stanley J. Goldsmith M.D.
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Correspondence to Stanley J. Goldsmith M.D. .

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Editors and Affiliations

  1. Tirocenter Nuclear Medicine Center, Adnan Saygun Cad. 3, Istanbul, 34340, Turkey

    Cumali Aktolun

  2. & Molecular Imaging, New York-Presbyterian Hospital, Division of Nuclear Medicine, East 68th Street 525, New York, 10065, New York, USA

    Stanley J. Goldsmith

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Goldsmith, S.J. (2013). Radioimmunotherapy of Lymphoma. In: Aktolun, C., Goldsmith, S. (eds) Nuclear Medicine Therapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-4021-5_1

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  • DOI: https://doi.org/10.1007/978-1-4614-4021-5_1

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