Treatment challenges in the management of relapsed or refractory non-Hodgkin's lymphoma - Novel and emerging therapies

Cancer Management and Research

Volumn 5, Issue 1, 2013, Pages 251-269

  Chao, Mark P ^a  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Non Hodgkin's lymphoma; Novel therapies; Relapsed refractory disease

Indexed keywords

ALEMTUZUMAB; BENDAMUSTINE; BORTEZOMIB; BRENTUXIMAB VEDOTIN; CARBOPLATIN; CHLORAMBUCIL; CISPLATIN; CYCLOPHOSPHAMIDE; CYTARABINE; DEXAMETHASONE; DOXORUBICIN; ETOPOSIDE; FLUDARABINE; GEMCITABINE; IBRITUMOMAB TIUXETAN; IFOSFAMIDE; LENALIDOMIDE; MEPREDNISONE; METHYLPREDNISOLONE; MITOXANTRONE; OFATUMUMAB; OXALIPLATIN; PENTOSTATIN; PREDNISONE; PROCARBAZINE; RITUXIMAB; THALIDOMIDE; TOSITUMOMAB I 131; UNINDEXED DRUG; VINCRISTINE;

ABDOMINAL PAIN; ACUTE GRANULOCYTIC LEUKEMIA; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; BLOOD TOXICITY; CANCER CHEMOTHERAPY; CANCER PROGNOSIS; CANCER RESISTANCE; CHRONIC LYMPHATIC LEUKEMIA; CONSTIPATION; CYTOPENIA; DISEASE FREE SURVIVAL; DRUG DOSE REDUCTION; DRUG WITHDRAWAL; EVENT FREE SURVIVAL; FOLLICULAR LYMPHOMA; GENOTOXICITY; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; INFECTION; LARGE CELL LYMPHOMA; LIVER TOXICITY; LUNG DISEASE; LYMPHOCYTOMA; MANTLE CELL LYMPHOMA; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; MYELOABLATIVE CONDITIONING; MYELODYSPLASTIC SYNDROME; NEUROLOGIC DISEASE; NONHODGKIN LYMPHOMA; NONHUMAN; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PERIPHERAL T CELL LYMPHOMA; PROGRESSION FREE SURVIVAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RADIOIMMUNOTHERAPY; REDUCED INTENSITY CONDITIONING; REVIEW; SALVAGE THERAPY; T CELL LYMPHOMA; THROMBOSIS; UNSPECIFIED SIDE EFFECT;

EID: 84884585831     PISSN: None     EISSN: 11791322     Source Type: Journal    
DOI: 10.2147/CMAR.S34273     Document Type: Review

References (131)

1. Zelenetz AD, Abramson JS, Advani RH, et al. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010;8(3):288-334.
2. Jaffe ES, Harris NL, Stein H, Vardiman JW. World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Vol 3, 3rd ed. Lyon: IARC; 2001.
3. Coiffier B, Thieblemont C, Van Den Neste E, et al. 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(12):2040-2045.
4. Glennie MJ, French RR, Cragg MS, Taylor RP. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol. 2007;44(16): 3823-3837.
5. Davis TA, Grillo-López AJ, White CA, et al. Rituximab anti-CD20 monoclonal antibody therapy in non-Hodgkin's lymphoma: safety and efficacy of re-treatment. J Clin Oncol. 2000;18(17):3135-3143.
6. Martín A, Conde E, Arnan M, et al. R-ESHAP as salvage therapy for patients with relapsed or refractory diffuse large B-cell lymphoma: the influence of prior exposure to rituximab on outcome. A GEL/TAMO study. Haematologica. 2008;93(12):1829-1836.
7. Hagberg H, Gisselbrecht C. 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. 2006;17 Suppl 4:iv31-iv32.
8. Rezvani AR, Maloney DG. Rituximab resistance. Best Pract Res Clin Haematol. 2011;24(2):203-216.
9. Shimizu R, Kikuchi J, Wada T, Ozawa K, Kano Y, Furukawa Y. HDAC inhibitors augment cytotoxic activity of rituximab by upregulating CD20 expression on lymphoma cells. Leukemia. 2010;24(10):1760-1768.
10. Moskowitz CH, Bertino JR, Glassman JR, et al. 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(12):3776-3785.
11. Kewalramani T, Zelenetz AD, Nimer SD, et al. Rituximab and ICE as second-line therapy before autologous stem cell transplantation for relapsed or primary refractory diffuse large B-cell lymphoma. Blood. 2004;103(10):3684-3688.
12. Rai KR, Peterson BL, Appelbaum FR, et al. Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia. N Engl J Med. 2000;343(24):1750-1757.
13. Molica S. Progress in the treatment of chronic lymphocytic leukemia: results of the German CLL8 trial. Expert Rev Anticancer Ther. 2011; 11(9):1333-1340.
14. Catovsky D, Richards S, Matutes E, et al. Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial. Lancet. 2007;370(9583):230-239.
15. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26): 1910-1916.
16. van Oers MH, Klasa R, Marcus RE, et al. Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood. 2006;108(10):3295-3301.
17. Hagemeister FB. Treatment of relapsed aggressive lymphomas: regimens with and without high-dose therapy and stem cell rescue. Cancer Chemother Pharmacol. 2002;49 Suppl 1:S13-S20.
18. 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(23):1540-1545.
19. Peniket AJ, Ruiz de Elvira MC, Taghipour G, et al. An EBMT registry matched study of allogeneic stem cell transplants for lymphoma: allogeneic transplantation is associated with a lower relapse rate but a higher procedure-related mortality rate than autologous transplantation. Bone Marrow Transplant. 2003;31(8):667-678.
20. Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007;117(5):1137-1146.
21. Appelbaum FR. Hematopoietic cell transplantation for non-Hodgkin's lymphoma: yesterday, today, and tomorrow. J Clin Oncol. 2008;26(18): 2927-2929.
22. Brown JR. The treatment of relapsed refractory chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2011;2011: 110-118.
23. Mayes S, Brown N, Illidge TM. New antibody drug treatments for lymphoma. Expert Opin Biol Ther. 2011;11(5):623-640.
24. Cang S, Mukhi N, Wang K, Liu D. Novel CD20 monoclonal antibodies for lymphoma therapy. J Hematol Oncol. 2012;5:64.
25. Cheson BD. Ofatumumab, a novel anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. J Clin Oncol. 2010;28(21): 3525-3530.
26. Teeling JL, French RR, Cragg MS, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood. 2004;104(6):1793-1800.
27. Gupta IV, Jewell RC. Ofatumumab, the first human anti-CD20 monoclonal antibody for the treatment of B cell hematologic malignancies. Ann N Y Acad Sci. 2012;1263:43-56.
28. Coiffier B, Lepretre S, Pedersen LM, et al. Safety and efficacy of ofatumumab, a fully human monoclonal anti-CD20 antibody, in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: a phase 1-2 study. Blood. 2008;111(3):1094-1100.
29. Wierda WG, Kipps TJ, Mayer J, et al. Ofatumumab as single-agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28(10):1749-1755.
30. Wierda WG, Kipps TJ, Durig J, et al. Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia. Blood. 2011;117(24):6450-6458.
31. Czuczman MS, Fayad L, Delwail V, et al. Ofatumumab monotherapy in rituximab-refractory follicular lymphoma: results from a multicenter study. Blood. 2012;119(16):3698-3704.
32. Czuczman MS, Hess G, Gadeberg OV, et al. Chemoimmunotherapy with ofatumumab in combination with CHOP in previously untreated follicular lymphoma. Br J Haematol. 2012;157(4):438-445.
33. Morschhauser F, Marlton P, Vitolo U, et al. Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma. Ann Oncol. 2010;21(9): 1870-1876.
34. Goldenberg DM, Morschhauser F, Wegener WA. Veltuzumab (humanized anti-CD20 monoclonal antibody): characterization, current clinical results, and future prospects. Leuk Lymphoma. 2010;51(5):747-755.
35. Morschhauser F, Leonard JP, Fayad L, et al. Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma: phase I/II results. J Clin Oncol. 2009;27(20):3346-3353.
36. Tu X, LaVallee T, Lechleider R. CD22 as a target for cancer therapy. J Exp Ther Oncol. 2011;9(3):241-248.
37. Leonard JP, Link BK. Immunotherapy of non-Hodgkin's lymphoma with hLL2 (epratuzumab, an anti-CD22 monoclonal antibody) and Hu1D10 (apolizumab). Semin Oncol. 2002;29(1 Suppl 2):81-86.
38. Strauss SJ, Morschhauser F, Rech J, et al. Multicenter phase II trial of immunotherapy with the humanized anti-CD22 antibody, epratuzumab, in combination with rituximab, in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2006;24(24):3880-3886.
39. Gottlieb AB, Kang S, Linden KG, et al. Evaluation of safety and clinical activity of multiple doses of the anti-CD80 monoclonal antibody, galiximab, in patients with moderate to severe plaque psoriasis. Clin Immunol. 2004;111(1):28-37.
40. Vyth-Dreese FA, Boot H, Dellemijn TA, et al. Localization in situ of costimulatory molecules and cytokines in B-cell non-Hodgkin's lymphoma. Immunology. 1998;94(4):580-586.
41. Czuczman MS, Thall A, Witzig TE, et al. Phase I/II study of galiximab, an anti-CD80 antibody, for relapsed or refractory follicular lymphoma. J Clin Oncol. 2005;23(19):4390-4398.
42. Czuczman MS, Leonard JP, Jung S, et al. Phase II trial of galiximab (anti-CD80 monoclonal antibody) plus rituximab (CALGB 50402): Follicular Lymphoma International Prognostic Index (FLIPI) score is predictive of upfront immunotherapy responsiveness. Ann Oncol. 2012;23(9):2356-2362.
43. Ishida T, Utsunomiya A, Iida S, et al. Clinical significance of CCR4 expression in adult T-cell leukemia/lymphoma: its close association with skin involvement and unfavorable outcome. Clin Cancer Res. 2003;9(10 Pt 1):3625-3634.
44. Yamamoto K, Utsunomiya A, Tobinai K, et al. Phase I study of KW-0761, a defucosylated humanized anti-CCR4 antibody, in relapsed patients with adult T-cell leukemia-lymphoma and peripheral T-cell lymphoma. J Clin Oncol. 2010;28(9):1591-1598.
45. Ishida T, Joh T, Uike N, et al. Defucosylated anti-CCR4 monoclonal antibody (KW-0761) for relapsed adult T-cell leukemia-lymphoma: a multicenter phase II study. J Clin Oncol. 2012;30(8):837-842.
46. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J Clin Oncol. 2010;28(12):2085-2093.
47. Fayad L, Patel H, Verhoef G, et al. Safety and clinical activity of the anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) in combination with rituximab in follicular lymphoma or diffuse large B-cell lymphoma: preliminary report of a phase 1/2 study. ASH Annu Meet Abstr. 2008;112(11):266.
48. Clodi K, Younes A. Reed-Sternberg cells and the TNF family of receptors/ligands. Leuk Lymphoma. 1997;27(3-4):195-205.
49. Forero-Torres A, Leonard JP, Younes A, et al. A phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. Br J Haematol. 2009;146(2):171-179.
50. Blum KA, Jung SH, Johnson JL, et al. Serious pulmonary toxicity in patients with Hodgkin's lymphoma with SGN-30, gemcitabine, vinorelbine, and liposomal doxorubicin is associated with an FcgammaRIIIa-158 V/F polymorphism. Ann Oncol. 2010;21(11): 2246-2254.
51. Garnock-Jones KP. Brentuximab vedotin: a review of its use in patients with Hodgkin lymphoma and systemic anaplastic large cell lymphoma following previous treatment failure. Drugs. 2013;73(4):371-381.
52. Pro B, Advani R, Brice P, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30(18):2190-2196.
53. Viardot A, Goebeler M, Nopponey R, et al. Blinatumomab monotherapy shows efficacy in patients with relapsed diffuse large B cell lymphoma. ASH Annu Meet Abstr. 2011;188:1637.
54. Kaminski MS, Zelenetz AD, Press OW, et al. Pivotal study of iodine I 131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin's lymphomas. J Clin Oncol. 2001;19(19):3918-3928.
55. Fisher RI, Kaminski MS, Wahl RL, et al. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin's lymphomas. J Clin Oncol. 2005;23(30):7565-7573.
56. Horning SJ, Younes A, Jain V, et al. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol. 2005;23(4):712-719.
57. Witzig TE, Flinn IW, Gordon LI, et al. Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin's lymphoma. J Clin Oncol. 2002;20(15):3262-3269.
58. Gordon LI, Molina A, Witzig T, et al. Durable responses after ibritumomab tiuxetan radioimmunotherapy for CD20+ B-cell lymphoma: long-term follow-up of a phase 1/2 study. Blood. 2004;103(12): 4429-4431.
59. Press OW, Unger JM, Rimsza LM, et al. Phase III randomized intergroup trial of CHOP plus rituximab compared with CHOP chemotherapy plus (131)iodine-tositumomab for previously untreated follicular non-Hodgkin lymphoma: SWOG S0016. J Clin Oncol. 2013;31(3):314-320.
60. Witzig TE, White CA, Gordon LI, et al. Safety of yttrium-90 ibritumomab tiuxetan radioimmunotherapy for relapsed low-grade, follicular, or transformed non-Hodgkin's lymphoma. J Clin Oncol. 2003;21(7):1263-1270.
61. Goldsmith SJ. Radioimmunotherapy of lymphoma: Bexxar and Zevalin. Semin Nucl Med. 2010;40(2):122-135.
62. Bennett JM, Kaminski MS, Leonard JP, et al. Assessment of treatment-related myelodysplastic syndromes and acute myeloid leukemia in patients with non-Hodgkin lymphoma treated with tositumomab and iodine I131 tositumomab. Blood. 2005;105(12):4576-4582.
63. Czuczman MS, Emmanouilides C, Darif M, et al. Treatment-related myelodysplastic syndrome and acute myelogenous leukemia in patients treated with ibritumomab tiuxetan radioimmunotherapy. J Clin Oncol. 2007;25(27):4285-4292.
64. Rodon J, Dienstmann R, Serra V, Tabernero J. Development of PI3K inhibitors: lessons learned from early clinical trials. Nat Rev Clin Oncol. 2013;10(3):143-153.
65. Schatz JH. Targeting the PI3K/AKT/mTOR pathway in non-Hodgkin's lymphoma: results, biology, and development strategies. Curr Oncol Rep. 2011;13(5):398-406.
66. Engelman JA. Targeting PI3K signalling in cancer: opportunities, challenges and limitations. Nat Rev Cancer. 2009;9(8):550-562.
67. Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010;116(12):2078-2088.
68. Kahl B, Byrd JC, Flinn IW, et al. Clinical safety and activity in a phase 1 study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110delta, in patients with relapsed or refractory non-Hodgkin lymphoma. ASH Ann Meet Abstr. 2010;166:1777.
69. Furman RR, Byrd JC, Brown JR, et al. CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110delta, demonstrates clinical activity and pharmacodynamic effects in patients with relapsed or refractory chronic lymphocytic leukemia. ASH Ann Meet Abstr. 2010;116:55.
70. Coutre SE, Leonard JP, Furman RR, et al. Combinations of the selective phosphatidylinositol 3-kinase-delta (PI3 Kdelta) inhibitor GS-1101 (CAL-101) with rituximab and/or bendamustine are tolerable and highly active in patients with relapsed or refractory chronic lymphocytic leukemia (CLL): results from a phase I study. ASH Ann Meet Abstr. 2012;120:191.
71. Furman RR, Barrientos JC, Sharman JP, et al. A phase I/II study of the selective phosphatidylinositol 3-kinase-delta (PI3 Kdelta) inhibitor, GS-1101 (CAL-101), with ofatumumab in patients with previously treated chronic lymphocytic leukemia (CLL). J Clin Oncol. 2012;30 Suppl:6518.
72. Robak P, Robak T. A targeted therapy for protein and lipid kinases in chronic lymphocytic leukemia. Curr Med Chem. 2012;19(31): 5294-5318.
73. Richardson PG, Eng C, Kolesar J, Hideshima T, Anderson KC. Perifosine, an oral, anti-cancer agent and inhibitor of the Akt pathway: mechanistic actions, pharmacodynamics, pharmacokinetics, and clinical activity. Expert Opin Drug Metab Toxicol. 2012;8(5):623-633.
74. Guidetti A, Viviani S, Marchiano A, et al. Dual targeted therapy with the AKT inhibitor perifosine and the multikinase inhibitor sorafenib in patients with relapsed/refractory lymphomas: final results of a phase II trial. ASH Annu Meet Abstr. 2012;120:3679.
75. Conley ME, Dobbs AK, Farmer DM, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199-227.
76. Davis RE, Ngo VN, Lenz G, et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature. 2010;463(7277): 88-92.
77. Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31(1):88-94.
78. O'Brien S, Burger JA, Blum KA, et al. The Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 induces durable responses in relapsed or refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): follow-up of a phase Ib/II study. ASH Annu Meet Abstr. 2011;118:983.
79. Byrd JC, Furman RR, Coutre SE, et al. The Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 (P) in treatment-naive (TN) chronic lymphocytic leukemia (CLL) patients (pts): Interim results of a phase Ib/II study. J Clin Oncol. 2012;30 Suppl:6507.
80. O'Brien SM, Barrientos JC, Flinn IW, et al. Combination of the Bruton's tyrosine kinase (BTK) inhibitor PCI-32765 with bendamustine (B)/rituximab (R) (BR) in patients (Pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL): interim results of a phase Ib/II study J Clin Oncol. 2012;30 Suppl:6515.
81. Jaglowski SM, Jones JA, Flynn JM, et al. A phase Ib/II study evaluating activity and tolerability of BTK inhibitor PCI-32765 and ofatumumab in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and related diseases. J Clin Oncol. 2012;30 Suppl:6508.
82. Brown JR. Ibrutinib (PCI-32765), the first BTK (Bruton's tyrosine kinase) inhibitor in clinical trials. Curr Hematol Malig Rep. 2013;8(1): 1-6.
83. Brown JR, Sharman JP, Harb WA, et al. 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. 2012;30 Suppl:8032.
84. Kahan BD, Camardo JS. Rapamycin: clinical results and future opportunities. Transplantation. 2001;72(7):1181-1193.
85. Dudkin L, Dilling MB, Cheshire PJ, et al. Biochemical correlates of mTOR inhibition by the rapamycin ester CCI-779 and tumor growth inhibition. Clin Cancer Res. 2001;7(6):1758-1764.
86. Hipp S, Ringshausen I, Oelsner M, Bogner C, Peschel C, Decker T. Inhibition of the mammalian target of rapamycin and the induction of cell cycle arrest in mantle cell lymphoma cells. Haematologica. 2005;90(10):1433-1434.
87. Hess G, Herbrecht R, Romaguera J, et al. 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. 2009;27(23):3822-3829.
88. Smith SM, van Besien K, Karrison T, et al. Temsirolimus has activity in non-mantle cell non-Hodgkin's lymphoma subtypes: the University of Chicago phase II consortium. J Clin Oncol. 2010;28(31):4740-4746.
89. Witzig TE, Reeder CB, LaPlant BR, et al. A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma. Leukemia. 2011;25(2):341-347.
90. Zent CS, LaPlant BR, Johnston PB, et al. 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. 2010;116(9):2201-2207.
91. Macias-Perez IM, Flinn IW. B-cell receptor pathobiology and targeting in NHL. Curr Oncol Rep. 2012;14(5):411-418.
92. Friedberg JW, Sharman J, Sweetenham J, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood. 2010;115(13): 2578-2585.
93. AstraZeneca. Study to learn if 200 mg test drug (fostamatinib) helps people with large B-cell lymphoma, a type of blood cancer. Bethesda, MD: US National Library of Medicine; 2011 [updated June 4, 2013]. Available from: http://clinicaltrials.gov/show/NCT01499303. NLM identifier: NCT01499303. Accessed June 17, 2013.
94. AstraZeneca. A randomised double blind phase II trial to evaluate the efficacy of two doses of fostamatinib in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). NLM identifier: NCT01499303.
95. Gascoyne RD, Adomat SA, Krajewski S, et al. Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. Blood. 1997;90(1):244-251.
96. Stolz C, Hess G, Hahnel PS, et al. Targeting Bcl-2 family proteins modulates the sensitivity of B-cell lymphoma to rituximab-induced apoptosis. Blood. 2008;112(8):3312-3321.
97. Wobser M, Voigt H, Eggert AO, et al. Bcl-2 expression in rituximab refractory cutaneous B-cell lymphoma. Br J Cancer. 2007;96(10): 1540-1543.
98. Waters JS, Webb A, Cunningham D, et al. Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. J Clin Oncol. 2000;18(9): 1812-1823.
99. Pro B, Leber B, Smith M, et al. Phase II multicenter study of oblimersen sodium, a Bcl-2 antisense oligonucleotide, in combination with rituximab in patients with recurrent B-cell non-Hodgkin lymphoma. Br J Haematol. 2008;143(3):355-360.
100. O'Brien S, Moore JO, Boyd TE, et al. 5-Year survival in patients with relapsed or refractory chronic lymphocytic leukemia in a randomized, phase III trial of fludarabine plus cyclophosphamide with or without oblimersen. J Clin Oncol. 2009;27(31):5208-5212.
101. Wilson WH, O'Connor OA, Czuczman MS, et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010;11(12):1149-1159.
102. Kahl B, Roberts AW, Seymour JF, et al. Navitoclax (ABT-263) plus rituximab: interim results of a phase 1 study in patients with CD20-positive lymphoid malignancies. ASH Annu Meet Abstr. 2010;116:3943.
103. Tang J, Yan H, Zhuang S. Histone deacetylases as targets for treatment of multiple diseases. Clin Sci (Lond). 2013;124(11):651-662.
104. Kirschbaum M, Frankel P, Popplewell L, et al. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011;29(9):1198-1203.
105. Budde LE, Zhang MM, Shustov AR, et al. A phase I study of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma. Br J Haematol. 2013;161(2):183-191.
106. Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B-cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184-4190.
107. Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011;117(22):5827-5834.
108. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003;97(11):2869-2879.
109. Salvatorelli E, Menna P, Paz OG, et al. The novel anthracenedione, pixantrone, lacks redox activity and inhibits doxorubicinol formation in human myocardium: insight to explain the cardiac safety of pixantrone in doxorubicin-treated patients. J Pharmacol Exp Ther. 2013;344(2): 467-478.
110. Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185-229.
111. Cavalletti E, Crippa L, Mainardi P, et al. Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone. Invest New Drugs. 2007;25(3):187-195.
112. Borchmann P, Schnell R, Knippertz R, et al. Phase I study of BBR 2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma. Ann Oncol. 2001;12(5):661-667.
113. Pettengell R, Coiffier B, Narayanan G, et al. Pixantrone dimaleate versus other chemotherapeutic agents as a single-agent salvage treatment in patients with relapsed or refractory aggressive non-Hodgkin lymphoma: a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2012;13(7):696-706.
114. Paoluzzi L, O'Connor OA. Mechanistic rationale and clinical evidence for the efficacy of proteasome inhibitors against indolent and mantle cell lymphomas. BioDrugs. 2006;20(1):13-23.
115. Friedberg JW, Vose JM, Kelly JL, et al. The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma. Blood. 2011;117(10):2807-2812.
116. Ribrag V, Gisselbrecht C, Haioun C, et al. Efficacy and toxicity of 2 schedules of frontline rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone plus bortezomib in patients with B-cell lymphoma: a randomized phase 2 trial from the French Adult Lymphoma Study Group (GELA). Cancer. 2009;115(19):4540-4546.
117. de Vos S, Goy A, Dakhil SR, et al. Multicenter randomized phase II study of weekly or twice-weekly bortezomib plus rituximab in patients with relapsed or refractory follicular or marginal-zone B-cell lymphoma. J Clin Oncol. 2009;27(30):5023-5030.
118. Agathocleous A, Rohatiner A, Rule S, et al. Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia. Br J Haematol. 2010;151(4): 346-353.
119. Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006;24(30):4867-4874.
120. Zinzani PL, Pellegrini C, Merla E, et al. Bortezomib as salvage treatment for heavily pretreated relapsed lymphoma patients: a multicenter retrospective study. Hematol Oncol. Epub October 29, 2012.
121. Coiffier B, Osmanov EA, Hong X, et al. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial. Lancet Oncol. 2011;12(8):773-784.
122. Chiappella A, Vitolo U. Lenalidomide in diffuse large B-cell lymphomas. Adv Hematol. 2012;2012:498342.
123. Wiernik PH, Lossos IS, Tuscano JM, et al. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008;26(30):4952-4957.
124. Witzig TE, Vose JM, Zinzani PL, et al. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011;22(7):1622-1627.
125. Zinzani PL, Pellegrini C, Gandolfi L, et al. 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(6):462-466.
126. Wang M, Fayad L, Wagner-Bartak N, et al. Lenalidomide in combination with rituximab for patients with relapsed or refractory mantle-cell lymphoma: a phase 1/2 clinical trial. Lancet Oncol. 2012;13(7):716-723.
127. Chiappella A, Franceschetti S, Castellino A, Carella AM, et al. 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). Presented at: 54th ASH Annual Meeting and Exposition; December 8-11, 2012; Atlanta, GA, USA.
128. Micallef IN, Maurer MJ, Wiseman GA, et al. Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma. Blood. 2011;118(15):4053-4061.
129. Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30(6): 631-636.
130. Zinzani PL, Khuageva NK, Wang H, et al. Bortezomib plus rituximab versus rituximab in patients with high-risk, relapsed, rituximab-naive or rituximab-sensitive follicular lymphoma: subgroup analysis of a randomized phase 3 trial. J Hematol Oncol. 2012;5:67.
131. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology. Non-Hodgkin's Lymphomas Version 1.2013. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.