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Clinical Applications of Nuclear Medicine Targeted Therapy pp 431–441Cite as

Radioimmunotherapy in the Transplant Setting

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Abstract

High-dose chemotherapy (HDC) conditioning regimens with autologous stem cell transplantation (ASCT) or reduced intensity conditioning (RIC) with allogeneic stem cell transplantation (allo-SCT) are consolidate approaches for patients with chemotherapy-sensitive, relapsed, aggressive, or indolent non-Hodgkin’s lymphoma (NHL). These approaches have been shown to be the only curative option for the majority of patients. Despite results that can be achieved with SCT combined with HDC, there are some problems that may limit the utility of this approach for a broad patient population, for example, older age or comorbidities. Furthermore SCT has limited success in chemorefractory disease or in heavily pretreated patients; recurrent disease is the major cause of treatment failure and the majority of patients relapsed. Consequently, there is the need for other effective and well-tolerated modality that will eradicate disease thus improving outcomes for both unfit patients and younger with refractory disease. Because lymphomas are highly sensitive to radiation, radioimmunotherapy (RIT) has been used with great success in consolidation therapy, and there is great interest in exploring the use of RIT, either as a single agent or as part of a conditioning regimen for autologous SCT. RIT was also considered as part of RIC to reduce the toxic effects of HDC. The data so far suggest that the use of RIT in the autologous setting can improve clinical outcome with no added toxicity, whereas similar positive findings have been reported in studies of yttrium-90-ibritumomab tiuxetan combined with RIC and allograft SCT in high-risk patients.

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References

  1. Feugier P, Van Hoof A, Sebban C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l’Adulte. J Clin Oncol. 2005;23:4117–26.

    Article  CAS  PubMed  Google Scholar 

  2. Armitage JO. Treatment of non-Hodgkin’s lymphoma. N Engl J Med. 1993;328:1023–30.

    Article  CAS  PubMed  Google Scholar 

  3. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Non-Hodgkin’s lymphomas.

    Google Scholar 

  4. Baron F, Maris MB, Sandmaier BM, et al. Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning. J Clin Oncol. 2005;23:1993–2003.

    Article  PubMed  Google Scholar 

  5. Deconinck E, Foussard C, Milpied N, et al. High-dose therapy followed by autologous purged stem-cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by GOELAMS. Blood. 2005;105:3817–23.

    Article  CAS  PubMed  Google Scholar 

  6. Lenz G, Dreyling M, Schiegnitz E, et al. Myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission prolongs progression-free survival in follicular lymphoma: results of a prospective, randomized trial of the German Low-Grade Lymphoma Study Group. Blood. 2004;104:2667–74.

    Article  CAS  PubMed  Google Scholar 

  7. Sebban C, Mounier N, Brousse N, et al. Standard chemotherapy with interferon compared with CHOP followed by high-dose therapy with autologous stem cell transplantation in untreated patients with advanced follicular lymphoma: the GELF-94 randomized study from the Groupe d’Etude des Lymphomes de l’Adulte (GELA). Blood. 2006;108:2540–4.

    Article  CAS  PubMed  Google Scholar 

  8. Philip T, Guglielmi C, Hagenbeek A, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med. 1995;333:1540–5.

    Article  CAS  PubMed  Google Scholar 

  9. Bertz H, Zeiser R, Lange W, et al. Long-term follow-up after high-dose chemotherapy and autologous stem-cell transplantation for high-grade B-cell lymphoma suggests an improved outcome for high-risk patients with respect to the age-adjusted International Prognostic Index. Ann Oncol. 2004;15:1419–24.

    Article  CAS  PubMed  Google Scholar 

  10. Schouten HC, Kvaloy S, Sydes M, et al. The CUP trial: a randomized study analyzing the efficacy of high dose therapy and purging in low-grade non-Hodgkin’s lymphoma (NHL). Ann Oncol. 2000;11(Suppl 1):91–4.

    Article  PubMed  Google Scholar 

  11. Schouten HC, Qian W, Kvaloy S, et al. 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. 2003;21:3918–27.

    Article  CAS  PubMed  Google Scholar 

  12. Rohatiner AZS, Nadler L, Davies AJ, et al. Myeloablative therapy with autologous bone marrow transplantation for follicular lymphoma at the time of second or subsequent remission: long-term follow-up. J Clin Oncol. 2007;25:2554–9.

    Article  PubMed  Google Scholar 

  13. Gianni AM, Berinstein NL, Evans PA, et al. Stem-cell transplantation in non-Hodgkin’s lymphoma: improving outcome. Anti-Cancer Drugs. 2002;13(Suppl 2):S35–42.

    Article  CAS  PubMed  Google Scholar 

  14. Gribben JG, Freedman AS, Neuberg D, et al. Immunologic purging of marrow assessed by PCR before autologous bone marrow transplantation for B-cell lymphoma. N Engl J Med. 1991;325:1525–33.

    Article  CAS  PubMed  Google Scholar 

  15. Tomblyn MR, Ewell M, Bredeson C, et al. Autologous versus reduced-intensity allogeneic hematopoietic cell transplantation for patients with chemosensitive follicular non-Hodgkin lymphoma beyond first complete response or first partial response. Biol Blood Marrow Transplant. 2011;17(7):1051–7.

    Article  PubMed  Google Scholar 

  16. Weaver CH, Petersen FB, Appelbaum FR, et al. High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma. J Clin Oncol. 1994;12:2559–66.

    Article  CAS  PubMed  Google Scholar 

  17. Gisselbrecht C, Mounier N. Rituximab: enhancing outcome of autologous stem cell transplantation in non-Hodgkin’s lymphoma. Semin Oncol. 2003;30(Suppl 2):28–33.

    Article  CAS  Google Scholar 

  18. Stashenko P, Nadler LM, Hardy R, et al. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980;125:1678–85.

    Google Scholar 

  19. Gregory SA, Hohloch K, Gisselbrecht C, et al. Harnessing the energy: development of radioimmunotherapy for patients with non-Hodgkin’s lymphoma. Oncologist. 2009;14(Suppl 2):4–16.

    Google Scholar 

  20. Montoto S, Canals C, Rohatiner AZS, et al. Long-term follow-up of high-dose treatment with autologous haematopoietic progenitor cell support in 693 patients with follicular lymphoma: an EBMT registry study. Leukemia. 2007;21:2324–31.

    Google Scholar 

  21. 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;110:54–8.

    Google Scholar 

  22. Gisselbrecht C. Completing the picture: results of the GELA-Z-BEAM trial in follicular lymphoma. Presented at the EBMT 2008; Month dd,-dd 7777; location. Painting a brighter future: improving clinical outcomes in transplant patients with NHL and CLL. Google Scholar.

    Google Scholar 

  23. Gisselbrecht C, Bethge W, Duarte RF, et al. Current status and future perspectives for yttrium-90 (90Y)-ibritumomab tiuxetan in stem cell transplantation for non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2007;40:1007–17.

    Google Scholar 

  24. Gopal AK, Pagel JM, Rajendran JG, et al. Improving the efficacy of reduced intensity allogeneic transplantation for lymphoma using radioimmunotherapy. Biol Blood Marrow Transplant. 2006;12:697–702.

    Article  CAS  PubMed  Google Scholar 

  25. Shimoni A, Nagler A. Radioimmunotherapy and stem-cell transplantation in the treatment of aggressive B-cell lymphoma. Leuk Lymphoma. 2007;48:2110–20.

    Article  CAS  PubMed  Google Scholar 

  26. Khouri IF, Saliba RM, Hosing C, et al. Efficacy and safety of yttrium 90 (90Y) ibritumomab tiuxetan in autologous and nonmyeloablative stem cell transplantation (NST) for relapsed non-Hodgkin’s lymphoma (NHL). Blood. 2006;108. Abstract 315.

    Google Scholar 

  27. Nademanee A, Forman S, Molina A, et al. 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. 2005;106:2896–902.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Nademanee A, Raubitschek A, Molina A, et al. Updated results of high-dose yttrium 90 (90Y) ibritumomab tiuxetan with high-dose etoposide (VP-16) and cyclophosphamide (CY) followed by autologous hematopoietic cell transplant (AHSCT) for poor-risk or refractory B-cell non-Hodgkin’s lymphoma. Blood. 2007;110. Abstract 1891.

    Google Scholar 

  29. Vose JM, Bierman PJ, Enke C, et al. 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. 2005;23:461–7.

    Article  CAS  PubMed  Google Scholar 

  30. Krishnan A, Palmer JM, Tsai NC, et al. Matched-cohort analysis of autologous hematopoietic cell transplantation with radioimmunotherapy versus total body irradiation-based conditioning for poor-risk diffuse large cell lymphoma. Biol Blood Marrow Transplant. 2012;18:441–50.

    Article  PubMed  Google Scholar 

  31. Shimoni A, Zwas ST, Oksman Y, et al. Yttrium-90-ibritumomab tiuxetan (Zevalin) combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for chemo-refractory aggressive non-Hodgkin’s lymphoma. Exp Hematol. 2007;35:534–40.

    Article  CAS  PubMed  Google Scholar 

  32. 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;26:90–5.

    Article  CAS  PubMed  Google Scholar 

  33. Shimabukuro-Vornhagen A, Josting A, Hübel K, et al. Yttrium-90 ibritumomab tiuxetan combined with high-dose BEAM chemotherapy and autologous stem cell transplantation for relapsed/refractory B-cell non-Hodgkin’s lymphoma. J Clin Oncol. 2008;26(15 Suppl). Abstract 8615.

    Google Scholar 

  34. Vose J, Bierman P, Bociek G, et al. Radioimmunotherapy with 131-I tositumomab enhanced survival in good prognosis relapsed and high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving high-dose chemotherapy and autologous stem cell transplantation. J Clin Oncol. 2007;25(18 Suppl). Abstract 8013.

    Google Scholar 

  35. Voegeli M, Rondeau S. Berardi Vilei S, et al. Y90-Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05). Hematol Oncol. 2016 Sep 28. https://doi.org/10.1002/hon.2348.

    Google Scholar 

  36. Siddiqi T, Tsai NC, Palmer JM, Forman SJ, et al. Effect of radioimmunotherapy-based poor-risk molecular profiling in diffuse large B-cell lymphoma. 2012 Annual meeting of the American Society of Clinical Oncology. 2012.

    Google Scholar 

  37. Witzig TE, Hong F, Micallef IN, et al. A phase II trial of RCHOP followed by radioimmunotherapy for early stage (stages I/II) diffuse large B-cell non-Hodgkin lymphoma. Br J Haematol. 2015;170:679–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Shimoni A, Avivi I, Rowe JM, et al. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012;118(19):4706–14.

    Article  CAS  PubMed  Google Scholar 

  39. Hertzberg M, Gandhi MK, Trotman J, Australasian Leukaemia Lymphoma Group (ALLG), et al. Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14. Haematologica. 2017;102(2):356–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Briones J, Novelli S, García-Marco JA, et al. Grupo Español de Linfomas y Trasplante Autologo de Médula Ósea (GELTAMO). Haematologica. 2014;99(7):e126.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Krishnan AY, Palmer J, Nademanee A, et al. Phase II study of yttrium-90 ibritumomab tiuxetan plus high-dose BCNU, etoposide, cytarabine, and melphalan for non-hodgkin lymphoma: the role of histology. Biol Blood Marrow Transplant. 2017;23(6):922–9.

    Article  CAS  PubMed  Google Scholar 

  42. Wondergem MJ, Palmer JM, Shimoni A, et al. Autologous transplantation for transformed non-Hodgkin lymphoma using an yttrium-90 ibritumomab tiuxetan conditioning regimen. Biol Blood Marrow Transplant. 2014;20(12):2072–5.

    Article  PubMed  Google Scholar 

  43. Gopal AK, Rajendran JG, Gooley TA, et al. High-dose 131I tositumomab (anti-CD20) radioimmunotherapy and autologous hematopoietic stem-cell transplantation for adults ≥60 years old with relapsed or refractory B-cell lymphoma. J Clin Oncol. 2007;25:1396–402.

    Article  PubMed  Google Scholar 

  44. 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;16:3270–8.

    Article  CAS  PubMed  Google Scholar 

  45. Vanazzi A, Ferrucci P, Grana C, et al. High dose 90yttrium ibritumomab tiuxetan with PBSC support in refractory-resistant NHL patients [abstract 1890]. Presented at the 2008 American Society for Hematology Annual Meeting; December 6–9, 2008; San Francisco.

    Google Scholar 

  46. Swinnen LJ, Flinn IW, Kahl B, et al. Phase I trial of yttrium 90 ibritumomab tiuxetan 90Y-RIT with autologous stem cell transplantation (ASCT) in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL). J Clin Oncol. 2008;26(15 Suppl). Abstract 8565.

    Google Scholar 

  47. Devizzi L, Seregni E, Guidetti A, et al. High-dose yttrium-90-ibritumomab tiuxetan with tandem stem-cell reinfusion: an outpatient preparative regimen for autologous hematopoietic cell transplantation. J Clin Oncol. 2008;26(32):5175–82.

    Article  CAS  PubMed  Google Scholar 

  48. Devizzi L, Guidetti A, Seregni E, et al. Long-term results of autologous hematopoietic stem-cell transplantation after high-dose 90Y-ibritumomab tiuxetan for patients with poor-risk non-Hodgkin lymphoma not eligible for high-dose BEAM. J Clin Oncol. 2013;31(23):2974–6.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Press OW, Eary JF, Appelbaum FR, et al. Phase II trial of 131I-B1 (anti-CD20) antibody therapy with autologous stem cell transplantation for relapsed B cell lymphomas. Lancet. 1995;346:336–40.

    Article  CAS  PubMed  Google Scholar 

  50. Press OW, Eary JF, Appelbaum FR, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med. 1993;329:1219–24.

    Article  CAS  PubMed  Google Scholar 

  51. 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;27:1653–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wagner HN Jr, Wiseman GA, Marcus CS, et al. Administration guidelines for radioimmunotherapy of non-Hodgkin’s lymphoma with 90Y-labeled anti-CD20 monoclonal antibody. J Nucl Med. 2002;43:267–72.

    CAS  PubMed  Google Scholar 

  53. Meredith RF. Logistics of therapy with the ibritumomab tiuxetan regimen. Int J Radiat Oncol Biol Phys. 2006;66(2 suppl):S35–8.

    Article  CAS  PubMed  Google Scholar 

  54. 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;96:2934–42.

    CAS  PubMed  Google Scholar 

  55. Vose JM, Bierman PJ, Loberiza FR Jr, et al. Phase I trial of 90Y-ibritumomab tiuxetan in patients with relapsed B-cell non-Hodgkin’s lymphoma following high-dose chemotherapy and autologous stem cell transplantation. Leuk Lymphoma. 2007;48:683–90.

    Article  CAS  PubMed  Google Scholar 

  56. Kaminski MS, Estes J, Zasadny KR, et al. Radioimmunotherapy with iodine 131I tositumomab for relapsed or refractory B-cell non-Hodgkin lymphoma: updated results and long-term follow-up of the University of Michigan experience. Blood. 2000;96:1259–66.

    CAS  PubMed  Google Scholar 

  57. Jacobs SA, Vidnovic N, Joyce J, et al. Full-dose 90Y ibritumomab tiuxetan therapy is safe in patients with prior myeloablative chemotherapy. Clin Cancer Res. 2005;11(19 Suppl):7146s–50s.

    Article  CAS  PubMed  Google Scholar 

  58. Mondello P, Steiner N, Willenbacher W, et al. 90Y-ibritumomab-tiuxetan consolidation therapy for advanced-stage mantle cell lymphoma after first-line autologous stem cell transplantation: is it time for a step forward? Clin Lymphoma Myeloma Leuk. 2016;16(2):82–8.

    Article  PubMed  Google Scholar 

  59. Shimoni A, Zwas ST, Oksman Y, et al. Ibritumomab tiuxetan (Zevalin) combined with reduced intensity conditioning and allogeneic stem-cell transplantation (SCT) in patients with chemorefractory non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2008;41:355–61.

    Article  CAS  PubMed  Google Scholar 

  60. Bouabdallah K, Furst S, Asselineau J, Chevalier P, et al. 90Y-ibritumomab tiuxetan, fludarabine, busulfan and antithymocyte globulin reduced-intensity allogeneic transplant conditioning for patients with advanced and high-risk B-cell lymphomas. Ann Oncol. 2015;26(1):193–8.

    Article  CAS  PubMed  Google Scholar 

  61. Cabrero M, Martin A, Briones J, et al. Phase II study of yttrium-90-ibritumomab tiuxetan as part of reduced-intensity conditioning (with melphalan, fludarabine ± thiotepa) for allogeneic transplantation in relapsed or refractory aggressive B cell lymphoma: a GELTAMO trial. Biol Blood Marrow Transplant. 2017;23(1):53–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Hematology and BMT Unit, IRCCS Istituto Nazionale Tumori, Milan, Italy

    Liliana Devizzi

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  1. Liliana Devizzi
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Correspondence to Liliana Devizzi .

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Editors and Affiliations

  1. Department of Nuclear Medicine, Humanitas Gavazzeni Hospital, Bergamo, Italy

    Emilio Bombardieri

  2. Nuclear Medicine Therapy and Endocrinology, Istituto Nazionale dei Tumori, Milano, Italy

    Ettore Seregni

  3. Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy

    Laura Evangelista

  4. Nuclear Medicine Division, Istituto Nazionale dei Tumori, Milano, Italy

    Carlo Chiesa

  5. Nuclear Medicine, Humanitas Research Hospital, Rozzano, Milano, Italy

    Arturo Chiti

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Devizzi, L. (2018). Radioimmunotherapy in the Transplant Setting. In: Bombardieri, E., Seregni, E., Evangelista, L., Chiesa, C., Chiti, A. (eds) Clinical Applications of Nuclear Medicine Targeted Therapy . Springer, Cham. https://doi.org/10.1007/978-3-319-63067-0_32

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