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Future Directions in Aggressive Lymphomas

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Non-Hodgkin Lymphoma

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

New exciting discoveries have emerged in the field of aggressive ­lymphomas. A better understanding of the biology of lymphomas has been translated into clinical practice, and new drugs are emerging as a hope for better disease control. In this chapter, we review the new therapies for aggressive lymphomas, like proteasome inhibitors, B-cell receptor signaling inhibitors (Syk, Burton’s tyrosine kinase and protein kinase C inhibitors) and mammalian targets of rapamycin. Moreover, a concise review of the new monoclonal antibodies (MoAbs) and their new targets is presented. Immunomodulatory drugs like lenalidomide also have shown potential benefit in patients with aggressive lymphomas. Although more studies are necessary, these drugs will probably be incorporated in the management of aggressive lymphomas, with less toxic, targeted therapy.

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References

  1. Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic ­leukemia. Science 132:1497

    Google Scholar 

  2. Lugo TG, Pendergast AM, Muller AJ, Witte ON (1990) Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247:1079–1082

    CAS  PubMed  Google Scholar 

  3. Druker BJ, Talpaz M, Resta D et al (2001) Efficacy and safety of a specific inhibitor of the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037

    CAS  PubMed  Google Scholar 

  4. Coiffier B, Haioun C, Ketterer N et al (1998) Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood 92:1927–1932

    CAS  PubMed  Google Scholar 

  5. Sievers EL, Larson RA, Stadtmauer EA, the Mylotarg Study Group et al (2001) Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol 19:3244–3254

    CAS  PubMed  Google Scholar 

  6. Scott AM, Wolchok JD, Old LJ (2012) Antibody therapy of cancer. Nat Rev Cancer 12(4):278–287

    CAS  PubMed  Google Scholar 

  7. Wiseman GA, Gordon LI, Multani PS et al (2002) Ibritumomab tiuxetan radioimmunotherapy for patients with relapsed or refractory non-Hodgkin’s lymphoma and mild thrombocytopenia: a phase II multicenter trial. Blood 99:4336–4342

    CAS  PubMed  Google Scholar 

  8. Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) (2008) World Health Organization classification of tumors: tumours of the haematopoietic and lymphoid tissues. International Agency for Research on Cancer (IARC) Press, Lyon, France, pp 17–44

    Google Scholar 

  9. Au WY, Horsman DE, Gascoyne RD, Viswanatha DS, Klasa RJ, Connors JM (2004) The spectrum of lymphoma with 8q24 aberrations: a clinical, pathological and cytogenetic study of 87 consecutive cases. Leuk Lymphoma 45:519–528

    CAS  PubMed  Google Scholar 

  10. Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH et al (1998) Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Blood 92:3152–3162

    CAS  PubMed  Google Scholar 

  11. Le Gouill S, Talmant P, Touzeau C, Moreau A, Garand R, Juge-Morineau N et al (2007) The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement. Haematologica 92:1335–1342

    PubMed  Google Scholar 

  12. Kanungo A, Medeiros LJ, Abruzzo LV, Lin P (2006) Lymphoid neoplasms associated with concurrent t(14;18) and 8q24/c-MYC translocation generally have a poor prognosis. Mod Pathol 19:25–33

    CAS  PubMed  Google Scholar 

  13. Niitsu N, Okamoto M, Hirano M (2009) Clinical features and prognosis of de novo diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC translocations. Leukemia 23:777–783

    CAS  PubMed  Google Scholar 

  14. Alizadeh AA, Eisen MB, Davis RE et al (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511

    CAS  PubMed  Google Scholar 

  15. Rosenwald A, Wright G, Chan WC et al (2002) The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med 346:1937–1947

    PubMed  Google Scholar 

  16. Friedberg JW (2011) New strategies in diffuse large B-cell lymphoma: translating findings from gene expression analyses into clinical practice. Clin Cancer Res 17(19):6112–6117

    CAS  PubMed  Google Scholar 

  17. Orsborne C, Byers R (2011) Impact of gene expression profiling in lymphoma diagnosis and prognosis. Histopathology 58(1):106–127

    PubMed  Google Scholar 

  18. Lenz G, Wright G, Dave SS et al (2008) Lymphoma/leukemia molecular profiling project. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 359(22):2313–2323

    CAS  PubMed  Google Scholar 

  19. Thieblemont C, Briere J, Mounier N et al (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

    PubMed  Google Scholar 

  20. Warburg O, Geissler AW, Lorenz S (1967) [On growth of cancer cells in media in which glucose is replaced by galactose]. Hoppe Seylers Z Physiol Chem 348(12):1686–1687

    CAS  PubMed  Google Scholar 

  21. Histed SN, Lindenberg ML, Mena E, Turkbey B, Choyke PL, Kurdziel KA (2012) Review of functional/anatomical imaging in oncology. Nucl Med Commun 33(4):349–361

    PubMed  Google Scholar 

  22. Miller JC, Fischman AJ, Aquino SL, Blake MA, Thrall JH, Lee SI (2007) FDG-PET CT for tumor imaging. J Am Coll Radiol 4(4):256–259

    PubMed  Google Scholar 

  23. Blodgett TM, Meltzer CC, Townsend DW (2007) PET/CT: form and function. Radiology 242(2):360–385

    PubMed  Google Scholar 

  24. Cheson BD (2011) Role of functional imaging in the management of lymphoma. J Clin Oncol 29(14):1844–1854

    PubMed  Google Scholar 

  25. Cheson BD, Pfistner B, Juweid ME et al (2007) Revised response criteria for malignant lymphoma. J Clin Oncol 25(5):579–586

    PubMed  Google Scholar 

  26. Juweid ME, Stroobants S, Hoekstra OS et al (2007) Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 25(5):571–578

    PubMed  Google Scholar 

  27. Spaepen K, Stroobants S, Dupont P et al (2001) Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ((18F)FDG) after first line chemotherapy in non-Hodgkin’s lymphoma: is (18)FDG-PET a valid alternative to conventional diagnostic method? J Clin Oncol 19(2):4141–4149

    Google Scholar 

  28. Spaepen K, Stroobants S, Dupont P et al (2002) Early restaging positron emission tomography with (18)-fluorodeoxyglucose predicts outcome in patients with aggressive non-Hodgkin lymphoma. Ann Oncol 13(9):1356–1363

    CAS  PubMed  Google Scholar 

  29. Itti E, Lin C, Dupuis J et al (2009) Prognostic value of interim 18F-FDG PET in patients with diffuse large B-cell lymphoma: SUV-based assessment at 4 cycles of chemotherapy. J Nucl Med 50(4):527–533

    PubMed  Google Scholar 

  30. A study of two associations of rituximab and chemotherapy, with a PET-driven strategy, in lymphoma (LNH2007-3B). ClinicalTrials.gov. http://www.clinicaltrials.gov/ct2/show/NCT00498043. (2007) Last accessed on 07 Jan 2011.

  31. Tailoring treatment for B cell non-Hodgkin’s lymphoma based on PET scan results mid treatment. ClinicalTrials.gov. http://www.clinicaltrials.gov/ct2/show/NCT00324467. (2006) Last accessed 09 Jan 2010.

  32. Stewart DA, Duggan P, Bahlis NJ et al (2009) Interim restaging FDG-PET/CT to guide use of high dose sequential induction therapy with rituximab-dose-intensive cyclophosphamide, etoposide, cisplatin (RDICEP) and rituximab-carmustine, etoposide, cytarabine, melphalan (RBEAM) and autologous stem cell transplantation (ASCT) for poor prognosis diffuse large b-cell lymphoma (DLBCL). ClinicalTrials. Gov Identifier: NCT00530179. Blood 114:3414 (ASH Annual Meeting Abstracts)

    Google Scholar 

  33. Bhaumik SR, Malik S (2008) Diverse regulatory mechanisms of eukaryotic transcriptional activation by the proteasome complex. Crit Rev Biochem Mol Biol 43:419–433

    CAS  PubMed  Google Scholar 

  34. Frankland-Searby S, Bhaumik SR (2012) The 26S proteasome complex: an attractive target for cancer therapy. Biochim Biophys Acta 1825(1):64–76

    CAS  PubMed  Google Scholar 

  35. Sterz J, von Metzler I, Hahne JC et al (2008) The potential of proteasome inhibitors in cancer therapy. Expert Opin Investig Drugs 17(6):879–895

    CAS  PubMed  Google Scholar 

  36. Voorhees PM, Dees EC, O’Neil B, Orlowski RZ (2003) The proteasome as a target for cancer therapy. Clin Cancer Res 9:6316–6325

    CAS  PubMed  Google Scholar 

  37. Adams J, Palombella VJ, Sausville EA et al (1999) Proteasome inhibitors: a novel class of potent and effective antitumor agents. Cancer Res 59:2615–2622

    CAS  PubMed  Google Scholar 

  38. Salvat C, Aquaviva C, Jariel-Encontre I et al (1999) Are there multiple proteolytic pathways contributing to c-Fos, c-Jun and p53 protein degradation in vivo? Mol Biol Rep 26:45–51

    CAS  PubMed  Google Scholar 

  39. Karin M, Cao Y, Greten FR, Li ZW (2002) NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer 2:301–310

    CAS  PubMed  Google Scholar 

  40. Hosokawa Y, Seto M (2004) Nuclear factor kappaB activation and antiapoptosis in mucosa-associated lymphoid tissue lymphoma. Int J Hematol 80(3):215–223

    CAS  PubMed  Google Scholar 

  41. Martínez-Delgado B, Cuadros M, Honrado E et al (2005) Differential expression of NF-kappaB pathway genes among peripheral T-cell lymphomas. Leukemia 19(12):2254–2263

    PubMed  Google Scholar 

  42. Calado DP, Zhang B, Srinivasan L et al (2010) Constitutive canonical NF-κB activation cooperates with disruption of BLIMP1 in the pathogenesis of activated B cell-like diffuse large cell lymphoma. Cancer Cell 18(6):580–589

    CAS  PubMed  Google Scholar 

  43. Goy A, Younes A, McLaughlin P et al (2005) Phase II study of proteasome inhibitor ­bortezomib in relapsed or refractory B-cell non-Hodgkin’s lymphoma. J Clin Oncol 23:667–675

    CAS  PubMed  Google Scholar 

  44. Fisher RI, Bernstein SH, Kahl BS et al (2006) Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol 24(30):4867–4874

    PubMed  Google Scholar 

  45. 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

    CAS  PubMed  Google Scholar 

  46. 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

    CAS  PubMed  Google Scholar 

  47. Gururajan M, Jennings CD, Bondada S (2006) Cutting edge: constitutive B cell receptor signaling is critical for basal growth of B lymphoma. J Immunol 176:5715–5719

    CAS  PubMed  Google Scholar 

  48. Chen L, Monti S, Juszczynski P et al (2008) SYK-dependent tonic B-cell receptor signaling is a rational treatment target in diffuse large B-cell lymphoma. Blood 111:2230–2237

    CAS  PubMed  Google Scholar 

  49. Chen L, Juszczynski P, Takeyama K, Aguiar RC, Shipp MA (2006) Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell receptor signaling, and cellular proliferation. Blood 108:3428–3433

    CAS  PubMed  Google Scholar 

  50. Friedberg JW, Sharman J, Sweetenham J et al (2010) Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 115:2578–2585

    CAS  PubMed  Google Scholar 

  51. Feldman AL, Sun DX, Law ME et al (2008) Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas. Leukemia 22:1139–1143

    CAS  PubMed  Google Scholar 

  52. Vihinen M, Mattsson PT, Smith CI (2000) Bruton tyrosine kinase (BTK) in X-linked agammaglobulinemia (XLA). Front Biosci 5:D917–D928

    CAS  PubMed  Google Scholar 

  53. Winer ES, Ingham RR, Castillo JJ (2012) PCI-32765: a novel Bruton’s tyrosine kinase inhibitor for the treatment of lymphoid malignancies. Expert Opin Investig Drugs 21(3):355–361

    CAS  PubMed  Google Scholar 

  54. Byrd JC, Blum KA, Burger JA et al (2011) Activity and tolerability of the Bruton’s tyrosine kinase (Btk) inhibitor PCI-32765 in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): interim results of a phase Ib/II study. J Clin Oncol 29(suppl):6508

    Google Scholar 

  55. Wang L, Martin P, Blum KA et al (2011) The Bruton’s tyrosine kinase inhibitor PCI-32765 is highly active as single-agent therapy in previously-treated mantle cell lymphoma (MCL): preliminary results of a phase II trial. Blood 118:442

    Google Scholar 

  56. Staudt LM, Dunleavy K, Buggy JJ et al (2011) The Bruton’s tyrosine kinase (Btk) inhibitor PCI-32765 modulates chronic active BCR signaling and induces tumor regression in relapsed/refractory ABC DLBCL. Blood 118:2716

    Google Scholar 

  57. Goekjian PG, Jirousek MR (2001) Protein kinase C inhibitors as novel anticancer drugs. Expert Opin Investig Drugs 10:2117–2140

    CAS  PubMed  Google Scholar 

  58. McMahon G (2000) VEGF receptor signaling in tumor angiogenesis. Oncologist 5(Suppl 1):3–10

    CAS  PubMed  Google Scholar 

  59. Ma S, Rosen ST (2007) Enzastaurin. Curr Opin Oncol 19:590–595

    CAS  PubMed  Google Scholar 

  60. Robertson MJ, Kahl BS, Vose JM et al (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 25:1741–1746

    CAS  PubMed  Google Scholar 

  61. Hagemeister FB (2010) Maintenance and consolidation strategies in non-Hodgkin’s lymphoma: a review of the data. Curr Oncol Rep 12(6):395–401

    PubMed  Google Scholar 

  62. Kortmansky J, Schwartz GK (2003) Bryostatin-1: a novel PKC inhibitor in clinical development. Cancer Invest 21(6):924–936

    CAS  PubMed  Google Scholar 

  63. Whitesell L, Lindquist SL (2005) HSP90 and the chaperoning of cancer. Nat Rev Cancer 5:761–772

    CAS  PubMed  Google Scholar 

  64. Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92:1564–1572

    CAS  PubMed  Google Scholar 

  65. Valbuena JR, Rassidakis GZ, Lin P et al (2005) Expression of heat-shock protein-90 in ­non-Hodgkin’s lymphomas. Mod Pathol 18:1343–1349

    CAS  PubMed  Google Scholar 

  66. Georgakis GV, Li Y, Younes A (2006) The heat shock protein 90 inhibitor 17-AAG induces cell cycle arrest and apoptosis in mantle cell lymphoma cell lines by depleting cyclin D1, Akt, Bid and activating caspase 9. Br J Haematol 135:68–71

    CAS  PubMed  Google Scholar 

  67. Solit DB, Chiosis G (2008) Development and application of Hsp90 inhibitors. Drug Discov Today 13:38–43

    CAS  PubMed  Google Scholar 

  68. Richardson PG, Chanan-Khan A, Lonial S, Krishman A, Carroll M, Cropp GF, Kersey K, Abitar M, Johnson RG, Hannah AL et al (2007) Tanespimycin (T)  +  bortezomib (BZ) in multiple myeloma (MM): confirmation of the recommended dose using a novel formulation. Blood 110:1165, ASH Annual Meeting Abstracts

    Google Scholar 

  69. Modi S, Stopeck AT, Gordon MS, Mendelson D, Solit DB, Bagatell R, Ma W, Wheler J, Rosen N, Norton L et al (2007) Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: a phase I dose-escalation study. J Clin Oncol 25:5410–5417

    CAS  PubMed  Google Scholar 

  70. Paez J, Sellers WR (2003) PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res 115:145–167

    CAS  PubMed  Google Scholar 

  71. Wlodarski P, Kasprzycka M, Liu X et al (2005) Activation of mammalian target of rapamycin in transformed B lymphocytes is nutrient dependent but independent of Akt, mitogen-activated protein kinase/extracellular signal-regulated kinase, insulin growth factor-I, and serum. Cancer Res 65:7800–7808

    CAS  PubMed  Google Scholar 

  72. Bertoni F, Zucca E, Cotter FE (2004) Molecular basis of mantle cell lymphoma. Br J Haematol 124:130–140

    CAS  PubMed  Google Scholar 

  73. Bjornsti MA, Houghton PJ (2004) The TOR pathway: a target for cancer therapy. Nat Rev Cancer 4:335–348

    CAS  PubMed  Google Scholar 

  74. Witzig TE, Geyer SM, Ghobrial I et al (2005) Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 23:5347–5356

    CAS  PubMed  Google Scholar 

  75. Hess G, Herbrecht R, Romaguera J et al (2009) Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol 27:3822–3829

    CAS  PubMed  Google Scholar 

  76. Ansell SM, Tang H, Kurtin P et al (2009) A phase II study of temsirolimus (CCI-779) in combination with rituximab in patients with relapsed or refractory mantle cell lymphoma [Abstract]. Blood 114:166

    Google Scholar 

  77. Haritunians T, Mori A, O’Kelly J, Luong QT, Giles FJ, Koeffler HP (2007) Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma. Leukemia 21:333–339

    CAS  PubMed  Google Scholar 

  78. Jundt F, Raetzel N, Muller C et al (2005) A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein beta and NF- {kappa}B activity in Hodgkin and anaplastic large cell lymphomas. Blood 106:1801–1807

    CAS  PubMed  Google Scholar 

  79. Reeder CB, Gornet MK, Habermann TM et al (2007) A phase II trial of the oral mTOR inhibitor everolimus (RAD001) in relapsed aggressive non-Hodgkin lymphoma (NHL). Blood 110:Abstract 121

    Google Scholar 

  80. Zent CS, LaPlant BR, Johnston PB et al (2010) The treatment of recurrent/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) with everolimus results in clinical responses and mobilization of CLL cells into the circulation. Cancer 116:2201–2207

    PubMed  Google Scholar 

  81. Ghobrial IM, Gertz M, Laplant B et al (2010) Phase II trial of the oral mammalian target of rapamycin inhibitor everolimus in relapsed or refractory Waldenstrom macroglobulinemia. J Clin Oncol 28:1408–1414

    CAS  PubMed  Google Scholar 

  82. Witzig TE, Habermann TM, Reeder C et al (2009) A phase II trial of the oral mtor inhibitor everolimus in relapsed non-Hodgkin’s lymphoma and Hodgkin disease [Abstract]. Haematologia 94(Suppl 2):436

    Google Scholar 

  83. Menhert JM, Kelly WK (2007) Histone deacetylase inhibitors: biology and mechanism of action. Cancer J 13:23–29

    Google Scholar 

  84. Shaffer AL, Yu X, He Y et al (2000) BCL-6 represses genes that function in lymphocyte ­differentiation, inflammation, and cell cycle control. Immunity 13:199–212

    CAS  PubMed  Google Scholar 

  85. Olsen EA, Kim YH, Kuzel TM et al (2007) Phase IIB multicenter trial of Vorinostat in patients with persistent, progressive, or treatment refractory cutaneous T-cell lymphoma. J Clin Oncol 25:3109–3115

    CAS  PubMed  Google Scholar 

  86. Crump M, Coiffier B, Jacobsen ED et al (2008) Phase II trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma. Ann Oncol 19:964–969

    CAS  PubMed  Google Scholar 

  87. Crump M, Andreadis C, Assouline S et al (2008) Treatment of relapsed or refractory non-Hodgkin lymphoma with the oral isotype-selective histone deacetylase inhibitor MGCD0103: interim results from a phase II study. J Clin Oncol 26(15 suppl):Abstract 8528

    Google Scholar 

  88. Lemoine M, Derenzini E, Buglio D, Medeiros LJ, Davis RE, Zhang J, Ji Y, Younes A (2012) The pan-deacetylase inhibitor panobinostat induces cell death and synergizes with everolimus in Hodgkin lymphoma cell lines. Blood 26:119(17):4017–4025

    Google Scholar 

  89. Corral LG, Muller GW, Moreira AL et al (1996) Selection of novel analogs of thalidomide with enhanced tumor necrosis factor alpha inhibitory activity. Mol Med 2:506–515

    CAS  PubMed  Google Scholar 

  90. Corral LG, Haslett PA, Muller GW et al (1999) Differential cytokine modulation and T cell activation by two distinct classes of thalidomide analogues that are potent inhibitors of TNF-alpha. J Immunol 163:380–386

    CAS  PubMed  Google Scholar 

  91. Haslett PA, Corral LG, Albert M et al (1998) Thalidomide costimulates primary human T lymphocytes, preferentially inducing proliferation, cytokine production, and cytotoxic responses in the CD8+ subset. J Exp Med 187:1885–1982

    CAS  PubMed  Google Scholar 

  92. Gupta D, Treon SP, Shima Y et al (2001) Adherence of multiple myeloma cells to bone marrow stromal cells upregulates vascular endothelial growth factor secretion: therapeutic applications. Leukemia 15:1950–1961

    CAS  PubMed  Google Scholar 

  93. Weber D, Chen C, Niesviyky R et al (2006) Lenalidomide plus high-dose dexamethasone versus dexamethasone alone for relapsed or refractory multiple myeloma (MM): results of North American phase III study (MM-009). J Clin Oncol 24:427s

    Google Scholar 

  94. Dimopoulos MA, Spenser A, Attal M et al (2005) Study of lenalidomide plus dexamethasone versus dexamethasone alone in relapsed or refractory multiple myeloma (MM): results of phase III study (MM-010). Proc Am Soc Hematol 106:6

    Google Scholar 

  95. Witzig TE, Vose JM, Zinzani PL et al (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

    CAS  PubMed  Google Scholar 

  96. Wang M, Fayad L, Hagemeister F et al (2007) A phase I/II study of lenalidomide in combination with rituximab in relapsed/refractory mantle cell lymphoma with early evidence of efficacy. J Clin Oncol 25(18 suppl):Abstract 8030

    Google Scholar 

  97. Nowakowski GS, Reeder CB, LaPlant B et al (2011) Combination of lenalidomide with R-CHOP (R2CHOP) as an initial therapy in aggressive lymphomas: a phase I/II study. J Clin Oncol 29(suppl):Abstract 8015

    Google Scholar 

  98. Hernandez-Ilizaliturri FJ, Deeb G, Zinzani PL et al (2011) Higher response to lenalidomide in elapsed/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

    CAS  PubMed  Google Scholar 

  99. Nightingale G (2011) Ofatumumab: a novel anti-CD20 monoclonal antibody for treatment of refractory chronic lymphocytic leukemia. Ann Pharmacother 45(10):1248–1255

    CAS  PubMed  Google Scholar 

  100. Sanford M, McCormack PL (2010) Ofatumumab. Drugs 70(8):1013–1019

    CAS  PubMed  Google Scholar 

  101. Czuczman MS, Fayad L, Delwail V et al (2012) Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood 119(16):3698–3704

    CAS  PubMed  Google Scholar 

  102. Coiffier B, Bosly A, Wu KL 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 116:Abstract 3955

    Google Scholar 

  103. Morschhauser F, Leonard JP, Fayad L et al (2009) Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin’s lymphoma: phase I/II results. J Clin Oncol 27(20):3346–3353

    CAS  PubMed  Google Scholar 

  104. Mössner E, Brünker P, Moser S et al (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

    PubMed  Google Scholar 

  105. Cartron G, Thieblemont C, Solal-Celigny P et al (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 (ASH Annual Meeting Abstracts)

    Google Scholar 

  106. Micallef IN, Maurer MJ, Wiseman GA et al (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

    CAS  PubMed  Google Scholar 

  107. Bhat S, Czuczman MS (2010) Galiximab: a review. Expert Opin Biol Ther 10(3):451–458

    CAS  PubMed  Google Scholar 

  108. Advani R, Forero-Torres A, Furman RR et al (2009) Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin’s lymphoma. J Clin Oncol 27(26):4371–4377

    CAS  PubMed  Google Scholar 

  109. Forero-Torres A, Bartlett NL, Nasta SD et al (2009) A phase 1b clinical trial of dacetuzumab in combination with rituximab and gemcitabine: multiple responses observed in patients with relapsed diffuse large b-cell lymphoma. Blood 114:586 (ASH Annual Meeting Abstracts)

    Google Scholar 

  110. Nagorsen D, Zugmaier G, Viardot A et al (2009) Confirmation of safety, efficacy and response duration in non-Hodgkin lymphoma patients treated with 60 μg/m2/d of BiTE® antibody Blinatumomab. Blood 114:2723 (ASH Annual Meeting Abstracts)

    Google Scholar 

  111. Dang NH, Smith MR, Offner F et al (2009) Anti-CD22 Immunoconjugate inotuzumab ozogamicin (CMC-544)  +  rituximab: clinical activity including survival in patients with recurrent/refractory follicular or ‘aggressive’ lymphoma. Blood 114:584 (ASH Annual Meeting Abstracts)

    Google Scholar 

  112. Shaffer AL, Rosenwald A, Staudt LM (2002) Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol 2(12):920–932

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology, Hospital Israelita Albert Einstein, Avenida Albert Einstein, 627—Morumbi, Sao Paulo, 05652-900, Brazil

    Guilherme F. Perini

  2. Department of Lymphoma/Myeloma, University of Texas M.D Anderson Cancer Center, Houston, TX, USA

    Luis E. Fayad

Authors
  1. Guilherme F. Perini
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  2. Luis E. Fayad
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Correspondence to Guilherme F. Perini .

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Editors and Affiliations

  1. Div. Hematology & Oncology, Rhode Island Hospital, Eddy St. 593, Providence, 02903, Rhode Island, USA

    Peter J. Quesenberry

  2. , Division of Hematology and Oncology, The Miriam Hospital, Summit Ave 164, Providence, 02906, Rhode Island, USA

    Jorge J. Castillo

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Perini, G.F., Fayad, L.E. (2013). Future Directions in Aggressive Lymphomas. In: Quesenberry, P., Castillo, J. (eds) Non-Hodgkin Lymphoma. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5851-7_10

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  • DOI: https://doi.org/10.1007/978-1-4614-5851-7_10

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