Background: Not all patients with diffuse large B-cell lymphoma (DLBCL) are candidates for aggressive regimens. 90Y ibritumomab tiuxetan (90Y-IT), an anti-CD20 radionuclide-conjugated antibody, has demonstrated clinical efficacy in DLBCL with a favorable toxicity profile. Methods: This phase II trial investigated the overall response rate (ORR), event-free survival (EFS), overall survival (OS) and toxicity of treatment with 90Y-IT (0.4 or 0.3 mCi 90Y/kg based on platelets) followed by rituximab maintenance therapy in patients with DLBCL not candidates for transplant. Results: 25 patients were enrolled. At best response 8 patients obtained a complete response (CR) and 1 a partial response (ORR 36%). Median EFS was 2.5 months and OS 8.1 months. No patient who obtained CR later relapsed systemically. Two patients were free of disease at the 61- and 100-month follow-ups; 65% had grade 3/4 thrombocytopenia, but no significant bleeding was observed. Grade 3 nonhematologic toxicity occurred in 36%. Patients who had progressed through a rituximab-containing regimen responded poorly. Conclusion: The ORR of 36% with 90Y-IT as salvage therapy for DLBCL while inferior to more aggressive regimens is significant with acceptable toxicity. For a subset of patients not candidates for salvage with autologous transplant, this treatment strategy can produce a durable, long-lasting remission.

Armitage JO, Weisenburger DD: New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998;16:2780-2795.
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM, Mize EM, Glick JH, Coltman CA Jr, Miller TP: Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma. N Engl J Med 1993;328:1002-1006.
Pfreundschuh M, Trumper L, Osterborg A, Pettengell R, Trneny M, Imrie K, Ma D, Gill D, Walewski J, Zinzani PL, Stahel R, Kvaloy S, Shpilberg O, Jaeger U, Hansen M, Lehtinen T, Lopez-Guillermo A, Corrado C, Scheliga A, Milpied N, Mendila M, Rashford M, Kuhnt E, Loeffler M: 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 2006;7:379-391.
Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S, Lefort S, Marit G, Macro M, Sebban C, Belhadj K, Bordessoule D, Ferme C, Tilly H: Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte. Blood 2010;116:2040-2045.
Coiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C: 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.
Moskowitz CH, Bertino JR, Glassman JR, Hedrick EE, Hunte S, Coady-Lyons N, Agus DB, Goy A, Jurcic J, Noy A, O'Brien J, Portlock CS, Straus DS, Childs B, Frank R, Yahalom J, Filippa D, Louie D, Nimer SD, Zelenetz AD: Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma. J Clin Oncol 1999;17:3776-3785.
Velasquez WS, McLaughlin P, Tucker S, Hagemeister FB, Swan F, Rodriguez MA, Romaguera J, Rubenstein E, Cabanillas F: ESHAP - an effective chemotherapy regimen in refractory and relapsing lymphoma: a 4-year follow-up study. J Clin Oncol 1994;12:1169-1176.
Cabanillas F, Velasquez WS, McLaughlin P, Jagannath S, Hagemeister FB, Redman JR, Swan F, Rodriguez MA: Results of recent salvage chemotherapy regimens for lymphoma and Hodgkin's disease. Semin Hematol 1988;25:47-50.
Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, Coiffier B, Biron P, Mandelli F, Chauvin F: Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med 1995;333:1540-1545.
Parker BA, Vassos AB, Halpern SE, Miller RA, Hupf H, Amox DG, Simoni JL, Starr RJ, Green MR, Royston I: Radioimmunotherapy of human B-cell lymphoma with 90Y-conjugated antiidiotype monoclonal antibody. Cancer Res 1990;50:1022S-1028S.
Weigert O, Illidge T, Hiddemann W, Dreyling M: Recommendations for the use of yttrium-90 ibritumomab tiuxetan in malignant lymphoma. Cancer 2006;107:686-695.
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;47:629-636.
Wagner HN Jr, Wiseman GA, Marcus CS, Nabi HA, Nagle CE, Fink-Bennett DM, Lamonica DM, Conti PS: Administration guidelines for radioimmunotherapy of non-Hodgkin's lymphoma with (90)Y-labeled anti-CD20 monoclonal antibody. J Nucl Med 2002;43:267-272.
Morschhauser F, Illidge T, Huglo D, Martinelli G, Paganelli G, Zinzani PL, Rule S, Liberati AM, Milpied N, Hess G, Stein H, Kalmus J, Marcus R: 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.
Witzig TE, Gordon LI, Cabanillas F, Czuczman MS, Emmanouilides C, Joyce R, Pohlman BL, Bartlett NL, Wiseman GA, Padre N, Grillo-Lopez AJ, 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;20:2453-2463.
Hohloch K, Delaloye AB, Windemuth-Kieselbach C, Gomez-Codina J, Linkesch W, Jurczak W, Cacchione R, Suh C, Zinzani PL, Trumper L: Radioimmunotherapy confers long-term survival to lymphoma patients with acceptable toxicity: registry analysis by the international radioimmunotherapy network. J Nucl Med 2011;52:1354-1360.
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J: Lymphoma classification - from controversy to consensus: the R.E.A.L. and WHO classification of lymphoid neoplasms. Ann Oncol 2000;11(suppl 1):3-10.
Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP: Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 1999;17:1244.
Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V: Revised response criteria for malignant lymphoma. J Clin Oncol 2007;25:579-586.
Philip T, Chauvin F, Armitage J, Bron D, Hagenbeek A, Biron P, Spitzer G, Velasquez W, Weisenburger DD, Fernandez-Ranada J: Parma international protocol: pilot study of DHAP followed by involved-field radiotherapy and BEAC with autologous bone marrow transplantation. Blood 1991;77:1587-1592.
Gisselbrecht C, Glass B, Mounier N, Gill D, Linch D, Trneny M, Bosly A, Shpilberg O, Ketterer N, Moskowitz C, Schmitz N: R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by autologous stem cell transplantation: CORAL study (abstract). J Clin Oncol 2009;27(15s):8509.
Hamlin PA, Rodriguez MA, Noy A, Portlock CS, Straus D, McLaughlin P, Pro B, Fayad L, Hagemeister FB, Wegner B, Dumitrescu O, Pandit Tasker N, Moskowitz CH, Zelenetz AD: Final results of a phase II study of sequential R-CHOP and yttrium-90 ibritumomab tiuxetan (RIT) for elderly high risk patients with untreated diffuse large B-cell lymphoma (DLBCL) (abstract). Blood 2010;116:1793.
Karmali R, Manson A, Bueschel K, Shell K, Gregory SA, O'Brien T, Shammo JM, Larson ML, Venugopal P: Phase II study of 2-weekly CHOP + rituximab followed by yttrium-90 ibritumomab tiuxetan (Zevalin) in patients with previously untreated diffuse large B cell lymphoma (DLBCL): final analysis (abstract). Blood 2010;116:3947.
Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ: Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 2006;24:3121-3127.
Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Milpied NJ, Radford J, Ketterer N, Shpilberg O, Duhrsen U, Hagberg H, Ma DD, Viardot A, Lowenthal R, Briere J, Salles G, Moskowitz CH, Glass B: Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. J Clin Oncol 2012;30:4462-4469.
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