Abstract
Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma subtype which requires immediate treatment. Standard treatment is usually a combined immune chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Since R-CHOP was approved, several attempts to combine it with novel agents and/or use them as maintenance therapy failed to improve the outcome. Recently, maintenance with lenalidomide after standard immune chemotherapy showed promising results. This review discusses the most pertinent published and running studies, analyzing study design, results, and practicality.
References
1.
Shah SR, Tran TM: Lenalidomide in myelodysplastic syndrome and multiple myeloma. Drugs 2007;67:1869-1881.
2.
Sehn LH, Donaldson J, Chhanabhai M, Fitzgerald C, Gill K, Klasa R, MacPherson N, O'Reilly S, Spinelli JJ, Sutherland J, Wilson KS, Gascoyne RD, Connors JM: Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia. J Clin Oncol 2005;23:5027-5033.
3.
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.
4.
Vitolo U, Trneny M, Belada D, Carella AM, Chua N, Abrisqueta P, Demeter J, Flinn IW, Hong XN, Kim WS, Pinto A, Burke JM, Shi Y, Tatsumi Y, Oestergaard M, Wenger MK, Fingerle-Rowson G, Catalani O, Nielsen T, Martelli M, Sehn LH: Obinutuzumab or rituximab plus CHOP in patients with previously untreated diffuse large B-cell lymphoma: final results from an open-label, randomized phase 3 study (GOYA). Blood 2016;128:470.
5.
van Imhoff GW, McMillan A, Matasar MJ, Radford J, Ardeshna KM, Kuliczkowski K, Kim W, Hong X, Goerloev JS, Davies A, Barrigon MD, Ogura M, Leppa S, Fennessy M, Liao Q, van der Holt B, Lisby S, Hagenbeek A: Ofatumumab versus rituximab salvage chemoimmunotherapy in relapsed or refractory diffuse large B-cell lymphoma: the ORCHARRD study. J Clin Oncol 2016, E-pub ahead of print.
6.
Salles G, Seymour JF, Offner F, Lopez-Guillermo A, Belada D, Xerri L, Feugier P, Bouabdallah R, Catalano JV, Brice P, Caballero D, Haioun C, Pedersen LM, Delmer A, Simpson D, Leppa S, Soubeyran P, Hagenbeek A, Casasnovas O, Intragumtornchai T, Ferme C, da Silva MG, Sebban C, Lister A, Estell JA, Milone G, Sonet A, Mendila M, Coiffier B, Tilly H: Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011;377:42-51.
7.
Jaeger U, Trneny M, Melzer H, Praxmarer M, Nawarawong W, Ben Yehuda D, Goldstein D, Mihaljevic B, Ilhan O, Ballova V, Hedenus M, Hsiao LT, Au WY, Burgstaller S, Weidinger G, Keil F, Dittrich C, Skrabs C, Klingler A, Chott A, Fridrik MA, Greil R: Rituximab maintenance for patients with aggressive B-cell lymphoma in first remission: results of the randomized NHL13 trial. Haematologica 2015;100:955-963.
8.
Crump M, Leppa S, Fayad L, Lee JJ, Di Rocco A, Ogura M, Hagberg H, Schnell F, Rifkin R, Mackensen A, Offner F, Pinter-Brown L, Smith S, Tobinai K, Yeh SP, Hsi ED, Nguyen T, Shi P, Hahka-Kemppinen M, Thornton D, Lin B, Kahl B, Schmitz N, Savage KJ, Habermann T: Randomized, double-blind, phase III trial of enzastaurin versus placebo in patients achieving remission after first-line therapy for high-risk diffuse large B-cell lymphoma. J Clin Oncol 2016;34:2484-2492.
9.
Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS: An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol 2011;22:1622-1627.
10.
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.
11.
Witzig TE, Tobinai K, Rigacci L, Lin TY, Ikeda T, Vanazzi A, Hino M, Shi Y, Mayer J, Costa LJ, Bermudez CD, Zhu J, Belada D, Bouabdallah K, Kattan JG, Wu C, Fan J, Louveau AL, Voi M, Cavalli F: PILLAR-2:A randomized, double-blind, placebo controlled, phase III study of adjuvant everolimus (EVE) in patients (pts) with poor-risk diffuse large B-cell lymphoma (DLBCL). J Clin Oncol 2016;34.
12.
Ferreri AJ, Sassone M, Zaja F, Re A, Spina M, Rocco AD, Fabbri A, Stelitano C, Frezzato M, Rusconi C, Zambello R, Couto S, Ren Y, Arcari A, Bertoldero G, Nonis A, Scarfo L, Calimeri T, Cecchetti C, Chiozzotto M, Govi S, Ponzoni M: Lenalidomide maintenance in patients with relapsed diffuse large B-cell lymphoma who are not eligible for autologous stem cell transplantation: an open label, single-arm, multicentre phase 2 trial. Lancet Haematol 2017;4:e137-e146.
13.
Thieblemont C, Tilly H, Gomes da Silva M, Casasnovas RO, Fruchart C, Morschhauser F, Haioun C, Lazarovici J, Grosicka A, Perrot A, Trotman J, Sebban C, Caballero D, Greil R, van Eygen K, Cohen AM, Gonzalez H, Bouabdallah R, Oberic L, Corront B, Choufi B, Lopez-Guillermo A, Catalano J, Van Hoof A, Briere J, Cabecadas J, Salles G, Gaulard P, Bosly A, Coiffier B: Lenalidomide maintenance compared with placebo in responding elderly patients with diffuse large B-cell lymphoma treated with first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. J Clin Oncol 2017:JCO2017726984.
14.
Kridel R, Mottok A, Farinha P, Ben-Neriah S, Ennishi D, Zheng Y, Chavez EA, Shulha HP, Tan K, Chan FC, Boyle M, Meissner B, Telenius A, Sehn LH, Marra MA, Shah SP, Steidl C, Connors JM, Scott DW, Gascoyne RD: Cell of origin of transformed follicular lymphoma. Blood 2015;126:2118-2127.
15.
Czuczman MS, Vose JM, Witzig TE, Zinzani PL, Buckstein R, Polikoff J, Li J, Pietronigro D, Ervin-Haynes A, Reeder CB: The differential effect of lenalidomide monotherapy in patients with relapsed or refractory transformed non-Hodgkin lymphoma of distinct histological origin. Br J Haematol 2011;154:477-481.
16.
Vitolo U, Chiappella A, Franceschetti S, Carella AM, Baldi I, Inghirami G, Spina M, Pavone V, Ladetto M, Liberati AM, Molinari AL, Zinzani P, Salvi F, Fattori PP, Zaccaria A, Dreyling M, Botto B, Castellino A, Congiu A, Gaudiano M, Zanni M, Ciccone G, Gaidano G, Rossi G: Lenalidomide plus R-CHOP21 in elderly patients with untreated diffuse large B-cell lymphoma: results of the REAL07 open-label, multicentre, phase 2 trial. Lancet Oncol 2014;15:730-737.
17.
Nowakowski GS, LaPlant B, Macon WR, Reeder CB, Foran JM, Nelson GD, Thompson CA, Rivera CE, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Gascoyne RD, Habermann TM, Witzig TE: Lenalidomide combined with R-CHOP overcomes negative prognostic impact of non-germinal center B-cell phenotype in newly diagnosed diffuse large B-cell lymphoma: a phase II study. J Clin Oncol 2015;33:251-257.
18.
Vose JM, Zhang MJ, Rowlings PA, Lazarus HM, Bolwell BJ, Freytes CO, Pavlovsky S, Keating A, Yanes B, van Besien K, Armitage JO, Horowitz MM: Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry. J Clin Oncol 2001;19:406-413.
19.
Hamlin PA, Zelenetz AD, Kewalramani T, Qin J, Satagopan JM, Verbel D, Noy A, Portlock CS, Straus DJ, Yahalom J, Nimer SD, Moskowitz CH: Age-adjusted international prognostic index predicts autologous stem cell transplantation outcome for patients with relapsed or primary refractory diffuse large B-cell lymphoma. Blood 2003;102:1989-1996.
20.
Thieblemont C, Coiffier B: Lymphoma in older patients. J Clin Oncol 2007;25:1916-1923.
21.
Zinzani PL, Pellegrini C, Gandolfi L, Stefoni V, Quirini F, Derenzini E, Broccoli A, Argnani L, Pileri S, Baccarani M: Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Clin Lymphoma Myeloma Leuk 2011;11:462-466.
22.
Feldman T, Mato AR, Chow KF, Protomastro EA, Yannotti KM, Bhattacharyya P, Yang X, Donato ML, Rowley SD, Carini C, Valentinetti M, Smith J, Gadaleta G, Bejot C, Stives S, Timberg M, Kdiry S, Pecora AL, Beaven AW, Goy A: Addition of lenalidomide to rituximab, ifosfamide, carboplatin, etoposide (RICER) in first-relapse/primary refractory diffuse large B-cell lymphoma. Br J Haematol 2014;166:77-83.
23.
Gribben JG, Fowler N, Morschhauser F: Mechanisms of action of lenalidomide in B-cell non-Hodgkin lymphoma. J Clin Oncol 2015;33:2803-2811.
24.
Mondello P, Steiner N, Willenbacher W, Ferrero S, Ghione P, Marabese A, Pitini V, Cuzzocrea S, Mian M: Lenalidomide in relapsed or refractory diffuse large B-cell lymphoma: is it a valid treatment option? Oncologist 2016;21:1107-1112.
© 2017 S. Karger AG, Basel
2017
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