Top

Published in:

01-04-2014 | Review Article

Accelerated therapeutic progress in diffuse large B cell lymphoma

Authors: Qingqing Cai, Jason Westin, Kai Fu, Madhav Desai, Liang Zhang, Huiqiang Huang, Wenqi Jiang, Rong Liang, Zhengzi Qian, Richard E. Champlin, Michael Wang

Published in: Annals of Hematology | Issue 4/2014

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma in the world. Clinically, biologically, and pathologically, DLBCL is a heterogeneous entity with a range of potential outcomes. Immunochemotherapy regimens, consisting of the chimeric monoclonal anti-CD20 antibody rituximab in combination with chemotherapy, have improved the outcomes. Relapsed DLBCL is generally treated with salvage immunochemotherapy followed by high-dose therapy and autologous stem cell transplantation; however, DLBCL is not yet curable in up to a third of patients. The real promise for cure lies in novel agents and their rational combinations. The improved understanding of DLBCL subtypes and gene expression profiling has led to the identification of targeted drugs that may allow for subtype specific therapy. We have summarized the existing data on the prognostic factors and the treatment of DLBCL, including the use of novel agents such as lenalidomide, carfilzomib, and ibrutinib. We also share our thoughts on the direction of future clinical trials.

The Non-Hodgkin’s Lymphoma Classification Project (1997) A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. Blood 89(11):3909–3918

Liu J, Song B, Fan T, Huang C, Xie C, Li J, Zhong W, Li S, Yu J (2011) Pathological and clinical characteristics of 1,248 non-Hodgkin’s lymphomas from a regional cancer hospital in Shandong, China. Asian Pac J Cancer Prev 12(11):3055–3061PubMed

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, Thiele J, JW V (2008) WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edn. IARC, Lyon

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 (2010) 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 116(12):2040–2045. doi:10.1182/blood-2010-03-276246 PubMedCentralPubMedCrossRef

Habermann TM, Weller EA, Morrison VA, Gascoyne RD, Cassileth PA, Cohn JB, Dakhil SR, Woda B, Fisher RI, Peterson BA, Horning SJ (2006) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. J Clin Oncol 24(19):3121–3127. doi:10.1200/JCO.2005.05.1003 PubMedCrossRef

Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, Lopez-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N, MabThera International Trial Group (2011) CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 12(11):1013–1022. doi:10.1016/S1470-2045(11)70235-2 PubMedCrossRef

Hagberg H, Gisselbrecht C, CORAL Study Group (2006) Randomised phase III study of R-ICE versus R-DHAP in relapsed patients with CD20 diffuse large B-cell lymphoma (DLBCL) followed by high-dose therapy and a second randomisation to maintenance treatment with rituximab or not: an update of the CORAL study. Ann Oncol 17(Suppl 4):iv31–iv32. doi:10.1093/annonc/mdj996 PubMedCrossRef

The International Non-Hodgkin’s Lymphoma Prognostic Factors Project (1993) A predictive model for aggressive non-Hodgkin’s lymphoma. N Engl J Med 329(14):987–994CrossRef

Ziepert M, Hasenclever D, Kuhnt E, Glass B, Schmitz N, Pfreundschuh M, Loeffler M (2010) Standard International prognostic index remains a valid predictor of outcome for patients with aggressive CD20+ B-cell lymphoma in the rituximab era. J Clin Oncol 28(14):2373–2380. doi:10.1200/JCO.2009.26.2493 PubMedCrossRef

10.

Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403(6769):503–511. doi:10.1038/35000501 PubMedCrossRef

11.

Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, Fisher RI, Gascoyne RD, Muller-Hermelink HK, Smeland EB, Giltnane JM, Hurt EM, Zhao H, Averett L, Yang L, Wilson WH, Jaffe ES, Simon R, Klausner RD, Powell J, Duffey PL, Longo DL, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Montserrat E, Lopez-Guillermo A, Grogan TM, Miller TP, LeBlanc M, Ott G, Kvaloy S, Delabie J, Holte H, Krajci P, Stokke T, Staudt LM, Lymphoma/Leukemia Molecular Profiling P (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346(25):1937–1947. doi:10.1056/NEJMoa012914 PubMedCrossRef

12.

Wright G, Tan B, Rosenwald A, Hurt EH, Wiestner A, Staudt LM (2003) A gene expression-based method to diagnose clinically distinct subgroups of diffuse large B cell lymphoma. Proc Natl Acad Sci U S A 100(17):9991–9996. doi:10.1073/pnas.1732008100 PubMedCentralPubMedCrossRef

13.

Kolbert CP, Feddersen RM, Rakhshan F, Grill DE, Simon G, Middha S, Jang JS, Simon V, Schultz DA, Zschunke M, Lingle W, Carr JM, Thompson EA, Oberg AL, Eckloff BW, Wieben ED, Li P, Yang P, Jen J (2013) Multi-platform analysis of microRNA expression measurements in RNA from fresh frozen and FFPE tissues. PLoS ONE 8(1):e52517. doi:10.1371/journal.pone.0052517 PubMedCentralPubMedCrossRef

14.

Barrans S, Worrillow L, Care M, Crouch S, Smith A, Patmore R, Davies A, Tooze R, Roman E, Jack A (2010) Gene Expression Profiling Using the Illumina ‘DASL’ Platform on RNA Extracted From Formalin Fixed Paraffin Embedded (FFPE) Tissue Identifies Distinct Prognostic Groups In CHOP-R Treated DLBCL. Blood (ASH Annual Meeting Abstracts) 116:Abstract 2485

15.

Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES, Pan Z, Farinha P, Smith LM, Falini B, Banham AH, Rosenwald A, Staudt LM, Connors JM, Armitage JO, Chan WC (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 103(1):275–282. doi:10.1182/blood-2003-05-1545 PubMedCrossRef

16.

Nyman H, Adde M, Karjalainen-Lindsberg ML, Taskinen M, Berglund M, Amini RM, Blomqvist C, Enblad G, Leppa S (2007) Prognostic impact of immunohistochemically defined germinal center phenotype in diffuse large B-cell lymphoma patients treated with immunochemotherapy. Blood 109(11):4930–4935. doi:10.1182/blood-2006-09-047068 PubMedCrossRef

17.

Ilic I, Mitrovic Z, Aurer I, Basic-Kinda S, Radman I, Ajdukovic R, Labar B, Dotlic S, Nola M (2009) Lack of prognostic significance of the germinal-center phenotype in diffuse large B-cell lymphoma patients treated with CHOP-like chemotherapy with and without rituximab. Int J Hematol 90(1):74–80. doi:10.1007/s12185-009-0353-y PubMedCrossRef

18.

Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H, Makino S, Eto T, Moriuchi Y, Taguchi F, Kamimura T, Tsuda H, Ogawa R, Shimoda K, Yamashita K, Suzuki K, Suzushima H, Tsukazaki K, Higuchi M, Utsunomiya A, Iwahashi M, Imamura Y, Tamura K, Suzumiya J, Yoshida M, Abe Y, Matsumoto T, Okamura T (2009) Prognostic impact of immunohistochemical biomarkers in diffuse large B-cell lymphoma in the rituximab era. Cancer Sci 100(10):1842–1847. doi:10.1111/j.1349-7006.2009.01268.x PubMedCrossRef

19.

Ott G, Ziepert M, Klapper W, Horn H, Szczepanowski M, Bernd HW, Thorns C, Feller AC, Lenze D, Hummel M, Stein H, Muller-Hermelink HK, Frank M, Hansmann ML, Barth TF, Moller P, Cogliatti S, Pfreundschuh M, Schmitz N, Trumper L, Loeffler M, Rosenwald A (2010) Immunoblastic morphology but not the immunohistochemical GCB/nonGCB classifier predicts outcome in diffuse large B-cell lymphoma in the RICOVER-60 trial of the DSHNHL. Blood 116(23):4916–4925. doi:10.1182/blood-2010-03-276766 PubMedCrossRef

20.

Fu K, Weisenburger DD, Choi WW, Perry KD, Smith LM, Shi X, Hans CP, Greiner TC, Bierman PJ, Bociek RG, Armitage JO, Chan WC, Vose JM (2008) Addition of rituximab to standard chemotherapy improves the survival of both the germinal center B-cell-like and non-germinal center B-cell-like subtypes of diffuse large B-cell lymphoma. J Clin Oncol 26(28):4587–4594. doi:10.1200/JCO.2007.15.9277 PubMedCrossRef

21.

Pfreundschuh M, Schubert J, Ziepert M, Schmits R, Mohren M, Lengfelder E, Reiser M, Nickenig C, Clemens M, Peter N, Bokemeyer C, Eimermacher H, Ho A, Hoffmann M, Mertelsmann R, Trumper L, Balleisen L, Liersch R, Metzner B, Hartmann F, Glass B, Poeschel V, Schmitz N, Ruebe C, Feller AC, Loeffler M, German High-Grade Non-Hodgkin Lymphoma Study G (2008) Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). Lancet Oncol 9(2):105–116. doi:10.1016/S1470-2045(08)70002-0 PubMedCrossRef

22.

Delarue R, Tilly H, Mounier N, Petrella T, Salles G, Thieblemont C, Bologna S, Ghesquieres H, Hacini M, Fruchart C, Ysebaert L, Ferme C, Casasnovas O, Van Hoof A, Thyss A, Delmer A, Fitoussi O, Molina TJ, Haioun C, Bosly A (2013) Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial. Lancet Oncol. doi:10.1016/S1470-2045(13)70122-0 PubMed

23.

Cunningham D, Hawkes EA, Jack A, Qian W, Smith P, Mouncey P, Pocock C, Ardeshna KM, Radford JA, McMillan A, Davies J, Turner D, Kruger A, Johnson P, Gambell J, Linch D (2013) Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone in patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma: a phase 3 comparison of dose intensification with 14-day versus 21-day cycles. Lancet. doi:10.1016/s0140-6736(13)60313-x

24.

Tilly H, Lepage E, Coiffier B, Blanc M, Herbrecht R, Bosly A, Attal M, Fillet G, Guettier C, Molina TJ, Gisselbrecht C, Reyes F, Groupe d’Etude des Lymphomes de lA (2003) Intensive conventional chemotherapy (ACVBP regimen) compared with standard CHOP for poor-prognosis aggressive non-Hodgkin lymphoma. Blood 102(13):4284–4289. doi:10.1182/blood-2003-02-0542 PubMedCrossRef

25.

Reyes F, Lepage E, Ganem G, Molina TJ, Brice P, Coiffier B, Morel P, Ferme C, Bosly A, Lederlin P, Laurent G, Tilly H, Groupe d’Etude des Lymphomes de lA (2005) ACVBP versus CHOP plus radiotherapy for localized aggressive lymphoma. N Engl J Med 352(12):1197–1205. doi:10.1056/NEJMoa042040 PubMedCrossRef

26.

Recher C, Coiffier B, Haioun C, Molina TJ, Ferme C, Casasnovas O, Thieblemont C, Bosly A, Laurent G, Morschhauser F, Ghesquieres H, Jardin F, Bologna S, Fruchart C, Corront B, Gabarre J, Bonnet C, Janvier M, Canioni D, Jais JP, Salles G, Tilly H, Groupe d’Etude des Lymphomes de lA (2011) Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet 378(9806):1858–1867. doi:10.1016/S0140-6736(11)61040-4 PubMedCrossRef

27.

Molina TJ, Canioni D, Copie-Bergman C, Recher C, Fournier M, Haioun C, Briere J, Berger F, Ferme C, Copin M-C, Casasnovas R-O, Thieblemont C, Leroy K, Salles GA, Jardin F, Jais J-P, Gaulard P, Coiffier B, Tilly H (2011) R-ACVBP Benefits to Younger Patients with Non-Germinal Centre Diffuse Large B-Cell Lymphoma As Compared to R-CHOP in the GELA Trial LNH03-2B. ASH Annual Meeting Abstracts 118 (21):2632-

28.

Molina JC, D, Copie-Bergman C (2011) R-ACVBP Benefits to younger patients with non-germinal centre diffuse large B-cell lymphoma as compared to R-CHOP in the GELA Trial LNH03-2B. Blood (ASH Annual Meeting Abstracts), Nov, vol. 118, p. 2632

29.

Ghielmini M, Vitolo U, Kimby E, Montoto S, Walewski J, Pfreundschuh M, Federico M, Hoskin P, McNamara C, Caligaris-Cappio F, Stilgenbauer S, Marcus R, Trneny M, Dreger P, Montserrat E, Dreyling M, Panel Members of the 1st ECCoML (2013) ESMO Guidelines consensus conference on malignant lymphoma 2011 part 1: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL). Ann Oncol 24(3):561–576. doi:10.1093/annonc/mds517 PubMedCrossRef

30.

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 (2007) 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 110(10.1182/blood-2007-01-068056):54–58PubMedCrossRef

31.

Zinzani PL, Rossi G, Franceschetti S, Botto B, Di Rocco A, Cabras MG, Petti MC, Stefoni V, Broccoli A, Fanti S, Pellegrini C, Montini GC, Gandolfi L, Derenzini E, Argnani L, Fina M, Tucci A, Bottelli C, Pileri S, Baccarani M (2010) Phase II trial of short-course R-CHOP followed by 90Y-ibritumomab tiuxetan in previously untreated high-risk elderly diffuse large B-cell lymphoma patients. Clin Cancer Res 16(15):3998–4004. doi:10.1158/1078-0432.CCR-10-0162 PubMedCrossRef

32.

Hamlin AP RM, Noy A (2010) 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). Blood (ASH Annual Meeting Abstracts), Nov, vol. 116, p. 1793

33.

Friedberg JW UJ, Burack WR, et al (2010) R-CHOP with Iodine-131 Tositumomab consolidation for advanced stage diffuse large B-cell lymphoma (DLBCL): Southwest Oncology Group Protocol S0433. Blood (ASH Annual Meeting Abstracts), Nov, vol. 116, p. 590

34.

Gianni AM, Bregni M, Siena S, Brambilla C, Di Nicola M, Lombardi F, Gandola L, Tarella C, Pileri A, Ravagnani F, Valagussa P, Bonadonna G (1997) High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma. N Engl J Med 336(18):1290–1297. doi:10.1056/NEJM199705013361804 PubMedCrossRef

35.

Milpied N, Deconinck E, Gaillard F, Delwail V, Foussard C, Berthou C, Gressin R, Lucas V, Colombat P, Harousseau JL, Groupe Ouest-Est des Leucemies et des Autres Maladies du Sang (2004) Initial treatment of aggressive lymphoma with high-dose chemotherapy and autologous stem-cell support. N Engl J Med 350(13):1287–1295. doi:10.1056/NEJMoa031770 PubMedCrossRef

36.

Martelli M, Gherlinzoni F, De Renzo A, Zinzani PL, De Vivo A, Cantonetti M, Falini B, Storti S, Meloni G, Rizzo M, Molinari AL, Lauria F, Moretti L, Lauta VM, Mazza P, Guardigni L, Pescarmona E, Pileri SA, Mandelli F, Tura S (2003) Early autologous stem-cell transplantation versus conventional chemotherapy as front-line therapy in high-risk, aggressive non-Hodgkin’s lymphoma: an Italian multicenter randomized trial. J Clin Oncol 21(7):1255–1262PubMedCrossRef

37.

Vitolo U, Liberati AM, Cabras MG, Federico M, Angelucci E, Baldini L, Boccomini C, Brugiatelli M, Calvi R, Ciccone G, Genua A, Deliliers GL, Levis A, Parvis G, Pavone E, Salvi F, Sborgia M, Gallo E, Intergruppo Italiano L (2005) High dose sequential chemotherapy with autologous transplantation versus dose-dense chemotherapy MegaCEOP as first line treatment in poor-prognosis diffuse large cell lymphoma: an “Intergruppo Italiano Linfomi” randomized trial. Haematologica 90(6):793–801PubMed

38.

Haioun C, Lepage E, Gisselbrecht C, Salles G, Coiffier B, Brice P, Bosly A, Morel P, Nouvel C, Tilly H, Lederlin P, Sebban C, Briere J, Gaulard P, Reyes F (2000) Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH87-2 protocol—a groupe d’Etude des lymphomes de l’Adulte study. J Clin Oncol 18(16):3025–3030PubMed

39.

Greb A, Bohlius J, Trelle S, Schiefer D, De Souza CA, Gisselbrecht C, Intragumtornchai T, Kaiser U, Kluin-Nelemans HC, Martelli M, Milpied NJ, Santini G, Verdonck LF, Vitolo U, Schwarzer G, Engert A (2007) High-dose chemotherapy with autologous stem cell support in first-line treatment of aggressive non-Hodgkin lymphoma—results of a comprehensive meta-analysis. Cancer Treat Rev 33(4):338–346. doi:10.1016/j.ctrv.2007.02.002 PubMedCrossRef

40.

Strehl J, Mey U, Glasmacher A, Djulbegovic B, Mayr C, Gorschluter M, Ziske C, Schmidt-Wolf IG (2003) High-dose chemotherapy followed by autologous stem cell transplantation as first-line therapy in aggressive non-Hodgkin’s lymphoma: a meta-analysis. Haematologica 88(11):1304–1315PubMed

41.

Le Gouill S, Milpied N, Lamy T, Delwail V, Gressin R, Guyotat D, Damaj G, Foussard C, Cartron G, Maisonneuve H (2011) First-line rituximab (R) high-dose therapy (R-HDT) versus R-CHOP 14 for young adults with diffuse large B-cell lymphoma: preliminary results of the GOELAMS 075 prospective multicenter randomized trial. J Clin Oncol 29:8003

42.

Schmitz N, Nickelsen M, Ziepert M, Haenel M, Borchmann P, Schmidt C, Viardot A, Bentz M, Peter N, Ehninger G, Doelken G, Ruebe C, Truemper L, Rosenwald A, Pfreundschuh M, Loeffler M, Glass B, German High-Grade Lymphoma Study G (2012) Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B-cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol 13(12):1250–1259. doi:10.1016/S1470-2045(12)70481-3 PubMedCrossRef

43.

Stiff P, Unger J, Cook J, Constine L, Couban S, Shea T, Winter J, Miller T, Tubbs R, Marcellus D (2011) Randomized phase III US/Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with highintermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). J Clin Oncol 29:8001

44.

Vitolo U CA, Brusamolino E et al (2012) Rituximab dose-dense chemotherapy followed by intensified high-dose chemotherapy and autologous stem cell transplantation (HDC + ASCT) significantly reduces the risk of progression compared to standard rituximab dose-dense chemotherapy as first line treatment in young patients with high-risk (aa-IPI 2-3) diffuse large b-cell lymphoma (DLBCL): final results of phase III randomized trial DLCL04 of the Fondazione Italiana Linfomi (FIL). Blood (ASH Annual Meeting Abstracts), Nov, vol. 120, p. 688

45.

Johnson ED, Sievert MC, McKinin EJ (1995) Retrieving research studies: a comparison of bibliographic and full-text versions of the New England Journal of Medicine. Proc Annu Symp Comput Appl Med Care, pp. 846–850

46.

Vellenga E, van Putten WL, van’t Veer MB, Zijlstra JM, Fibbe WE, van Oers MH, Verdonck LF, Wijermans PW, van Imhoff GW, Lugtenburg PJ, Huijgens PC (2008) Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood 111(2):537–543. doi:10.1182/blood-2007-08-108415 PubMedCrossRef

47.

Gisselbrecht C, Glass B, Mounier N, Singh Gill D, Linch DC, Trneny M, Bosly A, Ketterer N, Shpilberg O, Hagberg H, Ma D, Briere J, Moskowitz CH, Schmitz N (2010) Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol 28(27):4184–4190. doi:10.1200/JCO.2010.28.1618 PubMedCentralPubMedCrossRef

48.

Thieblemont C, Briere J, Mounier N, Voelker HU, Cuccuini W, Hirchaud E, Rosenwald A, Jack A, Sundstrom C, Cogliatti S, Trougouboff P, Boudova L, Ysebaert L, Soulier J, Chevalier C, Bron D, Schmitz N, Gaulard P, Houlgatte R, Gisselbrecht C (2011) The germinal center/activated B-cell subclassification has a prognostic impact for response to salvage therapy in relapsed/refractory diffuse large B-cell lymphoma: a bio-CORAL study. J Clin Oncol 29(31):4079–4087. doi:10.1200/jco.2011.35.4423 PubMedCrossRef

49.

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 (2012) 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 30(36):4462–4469. doi:10.1200/JCO.2012.41.9416 PubMedCentralPubMedCrossRef

50.

Vose JM, Carter S, Burns LJ, Ayala E, Press OW, Moskowitz CH, Stadtmauer EA, Mineshi S, Ambinder R, Fenske T, Horowitz M, Fisher R, Tomblyn M (2013) Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 Trial. J Clin Oncol 31(13):1662–1668. doi:10.1200/JCO.2012.45.9453 PubMedCrossRef

51.

Bishop MR, Dean RM, Steinberg SM, Odom J, Pavletic SZ, Chow C, Pittaluga S, Sportes C, Hardy NM, Gea-Banacloche J, Kolstad A, Gress RE, Fowler DH (2008) Clinical evidence of a graft-versus-lymphoma effect against relapsed diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell transplantation. Ann Oncol 19(11):1935–1940. doi:10.1093/annonc/mdn404 PubMedCentralPubMedCrossRef

52.

van Kampen RJ, Canals C, Schouten HC, Nagler A, Thomson KJ, Vernant JP, Buzyn A, Boogaerts MA, Luan JJ, Maury S, Milpied NJ, Jouet JP, Ossenkoppele GJ, Sureda A (2011) Allogeneic stem-cell transplantation as salvage therapy for patients with diffuse large B-cell non-Hodgkin’s lymphoma relapsing after an autologous stem-cell transplantation: an analysis of the European Group for Blood and Marrow Transplantation Registry. J Clin Oncol 29(10):1342–1348. doi:10.1200/JCO.2010.30.2596 PubMedCrossRef

53.

Bacher U, Klyuchnikov E, Le-Rademacher J, Carreras J, Armand P, Bishop MR, Bredeson CN, Cairo MS, Fenske TS, Freytes CO, Gale RP, Gibson J, Isola LM, Inwards DJ, Laport GG, Lazarus HM, Maziarz RT, Wiernik PH, Schouten HC, Slavin S, Smith SM, Vose JM, Waller EK, Hari PN, Lymphoma Working Committee of the C (2012) Conditioning regimens for allotransplants for diffuse large B-cell lymphoma: myeloablative or reduced intensity? Blood 120(20):4256–4262. doi:10.1182/blood-2012-06-436725 PubMedCentralPubMedCrossRef

54.

Ratanatharathorn V, Logan B, Wang D, Horowitz M, Uberti JP, Ringden O, Gale RP, Khoury H, Arora M, Spellman S, Cutler C, Antin J, Bornhauser M, Hale G, Verdonck L, Cairo M, Gupta V, Pavletic S, Center for International B, Marrow Transplant Research MWIUSA (2009) Prior rituximab correlates with less acute graft-versus-host disease and better survival in B-cell lymphoma patients who received allogeneic peripheral blood stem cell transplantation. Br J Haematol 145(6):816–824. doi:10.1111/j.1365-2141.2009.07674.x PubMedCentralPubMedCrossRef

55.

Gopal AK, Guthrie KA, Rajendran J, Pagel JM, Oliveira G, Maloney DG, Matesan MC, Storb RF, Press OW (2011) (9)(0)Y-Ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistent high-risk B-cell lymphoma. Blood 118(4):1132–1139. doi:10.1182/blood-2010-12-324392 PubMedCentralPubMedCrossRef

56.

Bethge WA, von Harsdorf S, Bornhauser M, Federmann B, Stelljes M, Trenschel R, Baurmann H, Dittmann H, Faul C, Vogel W, Kanz L, Bunjes D (2012) Dose-escalated radioimmunotherapy as part of reduced intensity conditioning for allogeneic transplantation in patients with advanced high-grade non-Hodgkin lymphoma. Bone Marrow Transplant 47(11):1397–1402. doi:10.1038/bmt.2012.62 PubMedCrossRef

57.

Papageorgiou SG, Cwynarski K, Kottaridis PD (2013) The role of allogeneic haematopoietic progenitor cell transplantation in patients with diffuse large B-cell non-Hodgkin lymphomas (DLBCL). Bone Marrow Transplant. doi:10.1038/bmt.2012.266 PubMed

58.

Thieblemont C, Delfau-Larue MH, Coiffier B (2012) Lenalidomide in diffuse large B-cell lymphoma. Adv Hematol 2012:861060. doi:10.1155/2012/861060 PubMedCentralPubMedCrossRef

59.

Rubenstein JL, Treseler PA, Stewart PJ (2011) Regression of refractory intraocular large B-cell lymphoma with lenalidomide monotherapy. J Clin Oncol 29(20):e595–e597. doi:10.1200/JCO.2011.34.7252 PubMedCentralPubMedCrossRef

60.

Zeldis JB, Knight R, Hussein M, Chopra R, Muller G (2011) A review of the history, properties, and use of the immunomodulatory compound lenalidomide. Ann N Y Acad Sci 1222:76–82. doi:10.1111/j.1749-6632.2011.05974.x PubMedCrossRef

61.

Zhang L, Qian Z, Cai Z, Sun L, Wang H, Bartlett JB, Yi Q, Wang M (2009) Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo. Am J Hematol 84(9):553–559. doi:10.1002/ajh.21468 PubMedCrossRef

62.

Qian Z, Zhang L, Cai Z, Sun L, Wang H, Yi Q, Wang M (2011) Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leuk Res 35(3):380–386. doi:10.1016/j.leukres.2010.09.027 PubMedCrossRef

63.

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 (2011) An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin’s lymphoma. Ann Oncol 22(7):1622–1627. doi:10.1093/annonc/mdq626 PubMedCrossRef

64.

Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L (2013) Oral Lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular, and transformed lymphoma: a phase II clinical trial. Leukemia. doi:10.1038/leu.2013.95

65.

Yang Y, Shaffer AL 3rd, Emre NC, Ceribelli M, Zhang M, Wright G, Xiao W, Powell J, Platig J, Kohlhammer H, Young RM, Zhao H, Yang Y, Xu W, Buggy JJ, Balasubramanian S, Mathews LA, Shinn P, Guha R, Ferrer M, Thomas C, Waldmann TA, Staudt LM (2012) Exploiting synthetic lethality for the therapy of ABC diffuse large B cell lymphoma. Cancer Cell 21(6):723–737. doi:10.1016/j.ccr.2012.05.024 PubMedCrossRef

66.

Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL, Pileri SA, Malik F, Macon WR, Goy A, Witzig TE, Czuczman MS (2011) Higher response to lenalidomide in relapsed/refractory diffuse large B-cell lymphoma in nongerminal center B-cell-like than in germinal center B-cell-like phenotype. Cancer 117(22):5058–5066. doi:10.1002/cncr.26135 PubMedCrossRef

67.

Nowakowski GS, LaPlant B, Habermann TM, Rivera CE, Macon WR, Inwards DJ, Micallef IN, Johnston PB, Porrata LF, Ansell SM, Klebig RR, Reeder CB, Witzig TE (2011) Lenalidomide can be safely combined with R-CHOP (R2CHOP) in the initial chemotherapy for aggressive B-cell lymphomas: phase I study. Leukemia 25(12):1877–1881. doi:10.1038/leu.2011.165 PubMedCrossRef

68.

Tilly H, Morschhauser F, Salles G, Casasnovas RO, Feugier P, Molina TJ, Jardin F, Terriou L, Haioun C, Coiffier B (2013) Phase 1b study of lenalidomide in combination with rituximab-CHOP (R2-CHOP) in patients with B-cell lymphoma. Leukemia 27(1):252–255. doi:10.1038/leu.2012.172 PubMedCrossRef

69.

Chiappella A FS, Castellino A, et al (2012) Rituximab-CHOP21 plus lenalidomide (LR-CHOP21) is effective and feasible in elderly untreated diffuse large B-cell lymphoma (DLBCL): results of phase II REAL07 study of the Fondazione Italiana Linfomi (FIL). Blood (ASH Annual Meeting Abstracts), Nov, vol. 120, p. 903

70.

Feldman T MR, Donato LM, et al (2012) Ricer (Rituximab, Ifosfamide, Carboplatin, Etoposide, Revlimid) Is Well-Tolerated Salvage Regimen in First Relapse/Primary Refractory DLBCL Allowing Consolidation with Autologous Stem Cell Transplant. Blood (ASH Annual Meeting Abstracts), Nov ; 120:3710

71.

Alduaij W, Illidge TM (2011) The future of anti-CD20 monoclonal antibodies: are we making progress? Blood 117(11):2993–3001. doi:10.1182/blood-2010-07-298356 PubMedCrossRef

72.

Alduaij W, Ivanov A, Honeychurch J, Cheadle EJ, Potluri S, Lim SH, Shimada K, Chan CH, Tutt A, Beers SA, Glennie MJ, Cragg MS, Illidge TM (2011) Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood 117(17):4519–4529. doi:10.1182/blood-2010-07-296913 PubMedCentralPubMedCrossRef

73.

Uchiyama S, Suzuki Y, Otake K, Yokoyama M, Ohta M, Aikawa S, Komatsu M, Sawada T, Kagami Y, Morishima Y, Fukui K (2010) Development of novel humanized anti-CD20 antibodies based on affinity constant and epitope. Cancer Sci 101(1):201–209. doi:10.1111/j.1349-7006.2009.01392.x PubMedCrossRef

74.

Barth MJ, Hernandez-Ilizaliturri FJ, Mavis C, Tsai PC, Gibbs JF, Deeb G, Czuczman MS (2012) Ofatumumab demonstrates activity against rituximab-sensitive and -resistant cell lines, lymphoma xenografts and primary tumour cells from patients with B-cell lymphoma. Br J Haematol 156(4):490–498. doi:10.1111/j.1365-2141.2011.08966.x PubMedCrossRef

75.

Coiffier B BA, Wu LK et al (2010) Ofatumumab monotherapy for treatment of patients with relapsed/progressive diffuse large B-cell lymphoma: results from a multicenter phase II study. Blood (ASH Annual Meeting Abstracts), Nov, vol. 116, p. 3955

76.

Matasar MJ, Czuczman MS, Rodriguez MA, Fennessy M, Shea TC, Spitzer G, Lossos IS, Kharfan-Dabaja MA, Joyce R, Fayad L, Henkel K, Liao Q, Edvardsen K, Jewell RC, Fecteau D, Singh RP, Lisby S, Moskowitz CH (2013) Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood. doi:10.1182/blood-2012-12-472027 PubMedCentralPubMed

77.

Matasar M, Czuczman M, Rodriguez M (2011) A phase II study of ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory aggressive B-cell lymphoma prior to autologous stem cell transplantation (ASCT). Blood 118(21):957

78.

Stein R, Qu Z, Chen S, Rosario A, Shi V, Hayes M, Horak ID, Hansen HJ, Goldenberg DM (2004) Characterization of a new humanized anti-CD20 monoclonal antibody, IMMU-106, and Its use in combination with the humanized anti-CD22 antibody, epratuzumab, for the therapy of non-Hodgkin’s lymphoma. Clin Cancer Res 10(8):2868–2878PubMedCrossRef

79.

Morschhauser F, Leonard JP, Fayad L, Coiffier B, Petillon MO, Coleman M, Schuster SJ, Dyer MJ, Horne H, Teoh N, Wegener WA, Goldenberg DM (2009) Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin’s lymphoma: phase I/II results. J Clin Oncol 27(20):3346–3353. doi:10.1200/JCO.2008.19.9117 PubMedCrossRef

80.

Robak T (2009) GA-101, a third-generation, humanized and glyco-engineered anti-CD20 mAb for the treatment of B-cell lymphoid malignancies. Curr Opin Investig Drugs 10(6):588–596PubMed

81.

Dalle S, Reslan L, Besseyre de Horts T, Herveau S, Herting F, Plesa A, Friess T, Umana P, Klein C, Dumontet C (2011) Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101. Mol Cancer Ther 10(1):178–185. doi:10.1158/1535-7163.MCT-10-0385 PubMedCrossRef

82.

Mossner E, Brunker P, Moser S, Puntener U, Schmidt C, Herter S, Grau R, Gerdes C, Nopora A, van Puijenbroek E, Ferrara C, Sondermann P, Jager C, Strein P, Fertig G, Friess T, Schull C, Bauer S, Dal Porto J, Del Nagro C, Dabbagh K, Dyer MJ, Poppema S, Klein C, Umana P (2010) Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 115(22):4393–4402. doi:10.1182/blood-2009-06-225979 PubMedCentralPubMedCrossRef

83.

Sehn LH, Assouline SE, Stewart DA, Mangel J, Gascoyne RD, Fine G, Frances-Lasserre S, Carlile DJ, Crump M (2012) A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood 119(22):5118–5125. doi:10.1182/blood-2012-02-408773 PubMedCrossRef

84.

Salles G, Morschhauser F, Lamy T, Milpied N, Thieblemont C, Tilly H, Bieska G, Asikanius E, Carlile D, Birkett J, Pisa P, Cartron G (2012) Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood 119(22):5126–5132. doi:10.1182/blood-2012-01-404368 PubMedCrossRef

85.

Cartron G, Thieblemont C, Solal-Celigny P, Morschhhauser F, Haioun C, Bouabdallah R, Lamy T, Milpied N, Gouill S, Feugier P (2010) Promising efficacy with the new anti-CD20 antibody GA101 in heavily pre-treated NHL patients—first results from a phase II study in patients with relapsed/refractory DLBCL and MCL. Blood 116(21):2878

86.

Carnahan J, Stein R, Qu Z, Hess K, Cesano A, Hansen HJ, Goldenberg DM (2007) Epratuzumab, a CD22-targeting recombinant humanized antibody with a different mode of action from rituximab. Mol Immunol 44(6):1331–1341. doi:10.1016/j.molimm.2006.05.007 PubMedCrossRef

87.

Micallef IN, Maurer MJ, Wiseman GA, Nikcevich DA, Kurtin PJ, Cannon MW, Perez DG, Soori GS, Link BK, Habermann TM, Witzig TE (2011) Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma. Blood 118(15):4053–4061. doi:10.1182/blood-2011-02-336990 PubMedCentralPubMedCrossRef

88.

Rajkumar SV, Richardson PG, Hideshima T, Anderson KC (2005) Proteasome inhibition as a novel therapeutic target in human cancer. J Clin Oncol 23(3):630–639. doi:10.1200/JCO.2005.11.030 PubMedCrossRef

89.

Dunleavy K, Pittaluga S, Czuczman MS, Dave SS, Wright G, Grant N, Shovlin M, Jaffe ES, Janik JE, Staudt LM, Wilson WH (2009) Differential efficacy of bortezomib plus chemotherapy within molecular subtypes of diffuse large B-cell lymphoma. Blood 113(24):6069–6076. doi:10.1182/blood-2009-01-199679 PubMedCentralPubMedCrossRef

90.

Davis RE, Brown KD, Siebenlist U, Staudt LM (2001) Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J Exp Med 194(12):1861–1874PubMedCentralPubMedCrossRef

91.

Ruan J, Martin P, Furman RR, Lee SM, Cheung K, Vose JM, Lacasce A, Morrison J, Elstrom R, Ely S, Chadburn A, Cesarman E, Coleman M, Leonard JP (2011) Bortezomib plus CHOP-rituximab for previously untreated diffuse large B-cell lymphoma and mantle cell lymphoma. J Clin Oncol 29(6):690–697. doi:10.1200/JCO.2010.31.1142 PubMedCrossRef

92.

Kortuem KM, Stewart AK (2013) Carfilzomib. Blood 121(6):893–897. doi:10.1182/blood-2012-10-459883 PubMedCrossRef

93.

Pham VL RA, Tamayo TA et al (2012) Biological significance of the immumoproteasome subunits Mecl-1 and LMP-2 in diffuse large B-cell lymphoma. Blood (ASH Annual Meeting Abstracts), Nov, vol. 120, p. 2717

94.

Davis RE, Ngo VN, Lenz G, Tolar P, Young RM, Romesser PB, Kohlhammer H, Lamy L, Zhao H, Yang Y, Xu W, Shaffer AL, Wright G, Xiao W, Powell J, Jiang JK, Thomas CJ, Rosenwald A, Ott G, Muller-Hermelink HK, Gascoyne RD, Connors JM, Johnson NA, Rimsza LM, Campo E, Jaffe ES, Wilson WH, Delabie J, Smeland EB, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pierce SK, Staudt LM (2010) Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 463(7277):88–92. doi:10.1038/nature08638 PubMedCentralPubMedCrossRef

95.

Efremov DG, Laurenti L (2011) The Syk kinase as a therapeutic target in leukemia and lymphoma. Expert Opin Investig Drugs 20(5):623–636. doi:10.1517/13543784.2011.570329 PubMedCrossRef

96.

McAdoo SP, Tam FW (2011) Fostamatinib Disodium. Drugs Future 36(4):273PubMedCentralPubMed

97.

Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, Lacasce A, Schaefer-Cutillo J, De Vos S, Sinha R, Leonard JP, Cripe LD, Gregory SA, Sterba MP, Lowe AM, Levy R, Shipp MA (2010) Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 115(13):2578–2585. doi:10.1182/blood-2009-08-236471 PubMedCentralPubMedCrossRef

98.

Bogusz AM, Baxter RH, Currie T, Sinha P, Sohani AR, Kutok JL, Rodig SJ (2012) Quantitative immunofluorescence reveals the signature of active B-cell receptor signaling in diffuse large B-cell lymphoma. Clin Cancer Res 18(22):6122–6135. doi:10.1158/1078-0432.CCR-12-0397 PubMedCrossRef

99.

Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH (2013) Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 31(1):88–94. doi:10.1200/JCO.2012.42.7906 PubMedCrossRef

100.

Wilson HW GF, Goy A et al (2012) The Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib (PCI-32765), has preferential activity in the ABC subtype of relapsed/refractory de novo diffuse large B-cell lymphoma (DLBCL): interim results of a multicenter, open-label, phase 2 study. Blood (ASH Annual Meeting Abstracts), Nov, vol. 120, p. 686

101.

Brown JR SJ, Harb WA et al (2012) Phase Ib trial of AVL-292, a covalent inhibitor of Bruton’s tyrosine kinase (Btk), in chronic lymphocytic leukemia (CLL) and B-non-Hodgkin lymphoma (B-NHL). J Clin Oncol 30 (suppl; abstr 8032)

102.

Uddin S, Hussain AR, Siraj AK, Manogaran PS, Al-Jomah NA, Moorji A, Atizado V, Al-Dayel F, Belgaumi A, El-Solh H, Ezzat A, Bavi P, Al-Kuraya KS (2006) Role of phosphatidylinositol 3'-kinase/AKT pathway in diffuse large B-cell lymphoma survival. Blood 108(13):4178–4186. doi:10.1182/blood-2006-04-016907 PubMedCrossRef

103.

Renne C, Willenbrock K, Martin-Subero JI, Hinsch N, Doring C, Tiacci E, Klapper W, Moller P, Kuppers R, Hansmann ML, Siebert R, Brauninger A (2007) High expression of several tyrosine kinases and activation of the PI3K/AKT pathway in mediastinal large B cell lymphoma reveals further similarities to Hodgkin lymphoma. Leukemia 21(4):780–787. doi:10.1038/sj.leu.2404594 PubMedCrossRef

104.

Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA (2011) CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 117(2):591–594. doi:10.1182/blood-2010-03-275305 PubMedCentralPubMedCrossRef

105.

Kahl B BC, Flinn WI et al (2010) Clinical safety and activity in a phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110, in patients with relapsed or refractory non-hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts), Nov, vol. 116, p. 1777

106.

Flinn WI HM, Patel M et al (2012) Clinical Safety and Activity in a Phase 1 Trial of IPI-145, a Potent Inhibitor of Phosphoinositide-3-Kinase-,, in Patients with Advanced Hematologic Malignancies. Blood (ASH Annual Meeting Abstracts), Nov 120:3663

107.

Thomson AW, Turnquist HR, Raimondi G (2009) Immunoregulatory functions of mTOR inhibition. Nat Rev Immunol 9(5):324–337. doi:10.1038/nri2546 PubMedCentralPubMedCrossRef

108.

Younes A (2008) Therapeutic activity of mTOR inhibitors in mantle cell lymphoma: clues but no clear answers. Autophagy 4(5):707–709PubMed

109.

Smith SM, van Besien K, Karrison T, Dancey J, McLaughlin P, Younes A, Smith S, Stiff P, Lester E, Modi S, Doyle LA, Vokes EE, Pro B (2010) Temsirolimus has activity in non-mantle cell non-Hodgkin’s lymphoma subtypes: The University of Chicago phase II consortium. J Clin Oncol 28(31):4740–4746. doi:10.1200/jco.2010.29.2813 PubMedCentralPubMedCrossRef

110.

Witzig TE, Reeder CB, LaPlant BR, Gupta M, Johnston PB, Micallef IN, Porrata LF, Ansell SM, Colgan JP, Jacobsen ED, Ghobrial IM, Habermann TM (2011) A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia 25(2):341–347. doi:10.1038/leu.2010.226 PubMedCentralPubMedCrossRef

111.

Robertson MJ, Kahl BS, Vose JM, de Vos S, Laughlin M, Flynn PJ, Rowland K, Cruz JC, Goldberg SL, Musib L, Darstein C, Enas N, Kutok JL, Aster JC, Neuberg D, Savage KJ, LaCasce A, Thornton D, Slapak CA, Shipp MA (2007) Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 25(13):1741–1746. doi:10.1200/JCO.2006.09.3146 PubMedCrossRef

112.

Hainsworth JD, Arrowsmith ER, Mccleod M (2011) Randomized phase II study of R-CHOP plus enzastaurin versus R-CHOP in the first-line treatment of patients with intermediate- and high-risk diffuse large B-cell lymphoma (DLBCL): Preliminary analysis. J Clin Oncol (Meeting Abstracts) 29(suppl; abstr 8016)

113.

Rigacci L, Puccini B, Cortelazzo S, Gaidano G, Piccin A, D’Arco A, Freilone R, Storti S, Orciuolo E, Zinzani PL, Zaja F, Bongarzoni V, Balzarotti M, Rota-Scalabrini D, Patti C, Gobbi M, Carpaneto A, Liberati AM, Bosi A, Iannitto E (2012) Bendamustine with or without rituximab for the treatment of heavily pretreated non-Hodgkin’s lymphoma patients : A multicenter retrospective study on behalf of the Italian Lymphoma Foundation (FIL). Ann Hematol 91(7):1013–1022. doi:10.1007/s00277-012-1422-5 PubMedCrossRef

114.

Ohmachi K, Niitsu N, Uchida T, Kim SJ, Ando K, Takahashi N, Takahashi N, Uike N, Eom HS, Chae YS, Terauchi T, Tateishi U, Tatsumi M, Kim WS, Tobinai K, Suh C, Ogura M (2013) Multicenter phase II study of bendamustine plus rituximab in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. doi:10.1200/jco.2012.46.5203 PubMed

115.

Cunningham D, Smith P, Mouncey P, Qian W, Jack A, Pocock C, Ardeshna K, Radford J, Davies A, McMillan A (2011) R-CHOP14 versus R-CHOP21: result of a randomized phase III trial for the treatment of patients with newly diagnosed diffuse large B-cell non-Hodgkin lymphoma. J Clin Oncol 29:8000a

Title: Accelerated therapeutic progress in diffuse large B cell lymphoma
Authors: Qingqing Cai
Jason Westin
Kai Fu
Madhav Desai
Liang Zhang
Huiqiang Huang
Wenqi Jiang
Rong Liang
Zhengzi Qian
Richard E. Champlin
Michael Wang
Publication date: 01-04-2014
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 4/2014
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-013-1979-7

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2014

Intracranial hemorrhage pattern in the patients with factor XIII deficiency

Impact of the duration of antiviral prophylaxis on rates of varicella-zoster virus reactivation disease in autologous hematopoietic cell transplantation recipients

Clinical implication of F-18 FDG PET/CT in patients with secondary hemophagocytic lymphohistiocytosis

Epidemiology of viral respiratory tract infections in an outpatient haematology facility

Severe immune thrombocytopenia secondary to Waldenström's macroglobulinemia with anti-GPIb/IX monoclonal IgM antibody

Single center experience with total body irradiation and melphalan (TBI-MEL) myeloablative conditioning regimen for allogeneic stem cell transplantation (SCT) in patients with refractory hematologic malignancies

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials