Future directions

In the current landscape, standardized treatment algorithms still lack sufficient evidence-based guidelines required to guide optimal therapy. Obinutuzumab, which has shown efficacy in FL, is currently being tested both in combination with chlorambucil and bendamustine in current Phase III trials for MZL.131,132 However, Herold et al recently reported the results of a subset of patients in the randomized Gallium trial comparing obinutuzumab or rituximab in patients with previously untreated advanced stage MZL.133 This study did show a significant difference in PFS between arms and actually showed increased frequency and severity of AEs.133 Other investigatory trials continue to be underway looking for other efficacious novel agents.

Continue Reading


MZL is a relatively rare and heterogeneous malignancy of B-cells that makes dedicated clinical trials difficult to perform and for which standardized treatment regimens are unfortunately lacking. Though each subtype has a unique initial treatment strategy based on limited-stage disease characteristics, with more advanced stage disease and R/R MZL, regimens used for advanced FL are usually employed. Though smaller studies have specifically looked at chemoimmunotherapy regimens for R/R MZL, consensus evidence-based guidelines on treatment specific to MZL are lacking. A recent pivotal Phase II trial has shown that single-agent ibrutinib is both a safe and efficacious treatment for all subtypes R/R MZL. Based on this, ibrutinib is rapidly gaining popularity as an agent of choice in MZL that progresses after rituximab-based therapy. Future studies will inform about the role of single-agent ibrutinib in both treatment-naïve patients, and its role in R/R MZL in combination with other agents.


The authors report no conflicts of interest in this work.

Nathan M. Denlinger, Narendranath Epperla, Basem M. William

Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center (OSUCCC-James), The Ohio State University, Columbus, OH, USA 


1. Swerdlow SH, Campo E, Pileri S, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–2390.

2. Al-Hamadani M, Habermann TM, Cerhan JR, Macon WR, Maurer MJ, Go RS. Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: a longitudinal analysis of the National Cancer Data Base from 1998 to 2011. Am J Hematol. 2015;90(9):790–795.

3. Weill JC, Weller S, Reynaud CA. Human marginal zone B cells. Annu Rev Immunol. 2009;27:267–285.

4. Quinn ER, Chan CH, Hadlock KG, Foung SK, Flint M, Levy S. The B-cell receptor of a hepatitis C virus (HCV)-associated non-Hodgkin lymphoma binds the viral E2 envelope protein, implicating HCV in lymphomagenesis. Blood. 2001;98(13):3745–3749.

5. Zucca E, Bertoni F, Roggero E, et al. Molecular analysis of the progression from Helicobacter pylori-associated chronic gastritis to mucosa-associated lymphoid-tissue lymphoma of the stomach. N Engl J Med. 1998;338(12):804–810.

6. Zucca E, Bertoni F, Vannata B, Cavalli F. Emerging role of infectious etiologies in the pathogenesis of marginal zone B-cell lymphomas. Clin Cancer Res. 4;20(20):5207–5216.

7. Kuo SH, Cheng AL. Helicobacter pylori and mucosa-associated lymphoid tissue: what’s new. Hematology Am Soc Hematol Educ Program. 2013;2013:109–117.

8. Khalil MO, Morton LM, Devesa SS, et al. Incidence of marginal zone lymphoma in the United States, 2001–2009 with a focus on primary anatomic site. Br J Haematol. 2014;165(1):67–77.

9. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) Research Data (1973–2014). In: National Cancer Institute D, Surveillance Research Program, ed released April 2017, based on the November 2016 submission.

10. Olszewski AJ, Castillo JJ. Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database. Cancer. 2013;119(3):629–638.

11. Niemann CU, Wiestner A. B-cell receptor signaling as a driver of lymphoma development and evolution. Semin Cancer Biol. 2013;23(6):410–421.

12. Noy A, de Vos S, Thieblemont C, et al. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017;129(16):2224–2232.

13. Yan Q, Huang Y, Watkins AJ, et al. BCR and TLR signaling pathways are recurrently targeted by genetic changes in splenic marginal zone lymphomas. Haematologica. 2012;97(4):595–598.

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

15. Cohen SM, Petryk M, Varma M, Kozuch PS, Ames ED, Grossbard ML. Non-Hodgkin’s lymphoma of mucosa-associated lymphoid tissue. Oncologist. 2006;11(10):1100–1117.

16. Dierlamm J, Baens M, Wlodarska I, et al. The apoptosis inhibitor gene API2 and a novel 18q gene, MLT, are recurrently rearranged in the t(11;18)(q21;q21) associated with mucosa-associated lymphoid tissue lymphomas. Blood. 1999;93(11):3601–3609.

17. Willis TG, Jadayel DM, Du MQ, et al. Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell. 1999;96(1):35–45.

18. Streubel B, Lamprecht A, Dierlamm J, et al. T(14;18)(q32;q21) involving IGH and MALT1 is a frequent chromosomal aberration in MALT lymphoma. Blood. 2003;101(6):2335–2339.

19. Rinaldi A, Mian M, Chigrinova E, et al. Genome-wide DNA profiling of marginal zone lymphomas identifies subtype-specific lesions with an impact on the clinical outcome. Blood. 2011;117(5):1595–1604.

20. Kwee I, Rancoita PM, Rinaldi A, et al. Genomic profiles of MALT lymphomas: variability across anatomical sites. Haematologica. 2011;96(7):1064–1066.

21. Suarez F, Lortholary O, Hermine O, Lecuit M. Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation. Blood. 2006;107(8):3034–3044.

22. O’Rourke JL. Gene expression profiling in Helicobacter-induced MALT lymphoma with reference to antigen drive and protective immunization. J Gastroenterol Hepatol. 2008;23(Suppl 2):S151–S156.

23. Bracci PM, Benavente Y, Turner JJ, et al. Medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project. J Natl Cancer Inst Monogr. 2014;2014(48):52–65.

24. Arcaini L, Burcheri S, Rossi A, et al. Prevalence of HCV infection in nongastric marginal zone B-cell lymphoma of MALT. Ann Oncol. 2007;18(2):346–350.

25. Arcaini L, Merli M, Volpetti S, Rattotti S, Gotti M, Zaja F. Indolent B-cell lymphomas associated with HCV infection: clinical and virological features and role of antiviral therapy. Clin Dev Immunol. 2012;2012:638185.

26. Hermine O, Lefrère F, Bronowicki JP, et al. Regression of splenic lymphoma with villous lymphocytes after treatment of hepatitis C virus infection. N Engl J Med. 2002;347(2):89–94.

27. Derringer GA, Thompson LD, Frommelt RA, Bijwaard KE, Heffess CS, Abbondanzo SL. Malignant lymphoma of the thyroid gland: a clinicopathologic study of 108 cases. Am J Surg Pathol. 2000;24(5):623–639.

28. Manganelli P, Fietta P, Quaini F. Hematologic manifestations of primary Sjögren’s syndrome. Clin Exp Rheumatol. 2006;24(4):438–448.

29. Zintzaras E, Voulgarelis M, Moutsopoulos HM. The risk of lymphoma development in autoimmune diseases: a meta-analysis. Arch Intern Med. 2005;165(20):2337–2344.

30. Nocturne G, Mariette X. Sjögren Syndrome-associated lymphomas: an update on pathogenesis and management. Br J Haematol. 2015;168(3):317–327.

31. Wang SS, Vajdic CM, Linet MS, et al. Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci. Am J Epidemiol. 2015;181(6):406–421.

32. Starr AG, Caimi PF, Fu P, et al. Dual institution experience of extranodal marginal zone lymphoma reveals excellent long-term outcomes. Bri J Haematol. 2016;173(3):404–412.

33. Zucca E, Copie-Bergman C, Ricardi U, et al. Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi144–vi148.

34. Zinzani PL. The many faces of marginal zone lymphoma. Hematol Am Soc Hematol Educ Program. 2012;2012:426–432.

35. Zucca E, Conconi A, Pedrinis E, et al. Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood. 2003;101(7):2489–2495.

36. Thieblemont C, Bastion Y, Berger F, et al. Mucosa-associated lymphoid tissue gastrointestinal and nongastrointestinal lymphoma behavior: analysis of 108 patients. J Clin Oncol. 1997;15(4):1624–1630.

37. Raderer M, Wöhrer S, Streubel B, et al. Assessment of disease dissemination in gastric compared with extragastric mucosa-associated lymphoid tissue lymphoma using extensive staging: a single-center experience. J Clin Oncol. 2006;24(19):3136–3141.

38. de Boer JP, Hiddink RF, Raderer M, et al. Dissemination patterns in non-gastric MALT lymphoma. Haematologica. 2008;93(2):201–206.

39. Boveri E, Arcaini L, Merli M, et al. Bone marrow histology in marginal zone B-cell lymphomas: correlation with clinical parameters and flow cytometry in 120 patients. Ann Oncol. 2009;20(1):129–136.

40. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin’s lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol. 1998;16(8):2780–2795.

41. Liu L, Wang H, Chen Y, Rustveld L, Liu G, Du XL. Splenic marginal zone lymphoma: a population-based study on the 2001–2008 incidence and survival in the United States. Leuk Lymphoma. 2013;54(7):1380–1386.

42. Thieblemont C, Felman P, Berger F, et al. Treatment of splenic marginal zone B-cell lymphoma: an analysis of 81 patients. Clin Lymphoma. 2002;3(1):41–47.

43. Arcaini L, Lazzarino M, Colombo N, et al. Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood. 2006;107(12):4643–4649.

44. Arcaini L, Paulli M, Boveri E, et al. Splenic and nodal marginal zone lymphomas are indolent disorders at high hepatitis C virus seroprevalence with distinct presenting features but similar morphologic and phenotypic profiles. Cancer. 2004;100(1):107–115.

45. Starr AG, Caimi PF, Fu P, et al. Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era. Hematology. 2017;22(7):405–411.

46. Parry-Jones N, Matutes E, Gruszka-Westwood AM, Swansbury GJ, Wotherspoon AC, Catovsky D. Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients. Br J Haematol. 2003;120(5):759–764.

47. Matutes E, Oscier D, Montalban C, et al. Splenic marginal zone lymphoma proposals for a revision of diagnostic, staging and therapeutic criteria. Leukemia. 2008;22(3):487–495.

48. Ponzoni M, Kanellis G, Pouliou E, et al. Bone marrow histopathology in the diagnostic evaluation of splenic marginal-zone and splenic diffuse red pulp small B-cell lymphoma: a reliable substitute for spleen histopathology? Am J Surg Pathol. 2012;36(11):1609–1618.

49. Arcaini L, Lucioni M, Boveri E, Paulli M. Nodal marginal zone lymphoma: current knowledge and future directions of an heterogeneous disease. Eur J Haematol. 2009;83(3):165–174.

50. Thieblemont C, Molina T, Davi F. Optimizing therapy for nodal marginal zone lymphoma. Blood. 2016;127(17):2064–2071.

51. Arcaini L, Paulli M, Burcheri S, et al. Primary nodal marginal zone B-cell lymphoma: clinical features and prognostic assessment of a rare disease. Br J Haematol. 2007;136(2):301–304.

52. van den Brand M, van der Velden WJ, Diets IJ, et al. Clinical features of patients with nodal marginal zone lymphoma compared to follicular lymphoma: similar presentation, but differences in prognostic factors and rate of transformation. Leuk Lymphoma. 2016;57(7):1649–1656.

53. Starr AG, Caimi PF, Fu P, et al. Dual institution experience of nodal marginal zone lymphoma reveals excellent long-term outcomes in the rituximab era. Br J Haematol. 2016;175(2):275–280.

54. Vallisa D, Bernuzzi P, Arcaini L, et al. Role of anti-hepatitis C virus (HCV) treatment in HCV-related, low-grade, B-cell, non-Hodgkin’s lymphoma: a multicenter Italian experience. J Clin Oncol. 2005;23(3):468–473.

55. Dreyling M, Thieblemont C, Gallamini A, et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma. Ann Oncol. 2013;24(4):857–877.

56. Vannata B, Zucca E. Hepatitis C virus-associated B-cell non-Hodgkin lymphomas. Hematology Am Soc Hematol Educ Program. 2014;2014(1):590–598.

57. Michot JM, Canioni D, Driss H, et al. Antiviral therapy is associated with a better survival in patients with hepatitis C virus and B-cell non-Hodgkin lymphomas, ANRS HC-13 lympho-C study. Am J Hematol. 2015;90(3):197–203.

58. Arcaini L, Besson C, Peveling-Oberhag J, et al. Anti-lymphoma activity of interferon-free antiviral treatment in patients with indolent B-cell lymphomas associated with hepatitis C virus infection. In: Besson C, editor. Vol 126. Blood Ame Soc Hematol. 2015;126:3938.

59. Tarella C, Arcaini L, Baldini L, et al. Italian Society of Hematology, Italian Society of Experimental Hematology, and Italian Group for Bone Marrow Transplantation guidelines for the management of indolent, nonfollicular B-cell lymphoma (marginal zone, lymphoplasmacytic, and small lymphocytic lymphoma). Clin Lymphoma Myeloma Leuk. 2015;15(2):75–85.

60. Arcaini L, Vallisa D, Rattotti S, et al. Antiviral treatment in patients with indolent B-cell lymphomas associated with HCV infection: a study of the Fondazione Italiana Linfomi. Ann Oncol. 2014;25(7):1404–1410.

61. Zullo A, Hassan C, Cristofari F, et al. Effects of Helicobacter pylori eradication on early stage gastric mucosa-associated lymphoid tissue lymphoma. Clin Gastroenterol Hepatol. 2010;8(2):105–110.

62. Malfertheiner P, Megraud F, O’Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut. 2007;56(6):772–781.

63. Chey WD, Wong BC, Gastroenterology PPCotACo. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–1825.

64. Ferreri AJ, Dolcetti R, Du MQ, et al. Ocular adnexal MALT lymphoma: an intriguing model for antigen-driven lymphomagenesis and microbial-targeted therapy. Ann Oncol. 2008;19(5):835–846.

65. Govi S, Dolcetti R, Ponzoni M, et al. Final results of a multicenter phase II trial with translational elements to investigate the possible infective causes of ocular adnexal marginal zone B-cell lymphoma (OAMZL) with particular reference to chlamydia species and the efficacy of doxycycline as first-line lymphoma treatment (the IELSG#27 TRIAL). In: Dolcetti R, editor. Vol 118. Blood Am Soc Hematol. 2011; 118:267.

66. Zullo A, Hassan C, Ridola L, et al. Eradication therapy in Helicobacter pylori-negative, gastric low-grade mucosa-associated lymphoid tissue lymphoma patients: a systematic review. J Clin Gastroenterol. 2013;47(10):824–827.

67. Kiesewetter B, Raderer M. Antibiotic therapy in nongastrointestinal MALT lymphoma: a review of the literature. Blood. 2013;122(8):1350–1357.

68. Lecuit M, Lortholary O. Immunoproliferative small intestinal disease associated with Campylobacter jejuni. Med Mal Infect. 2005;35(Suppl 2):S56–S58.

69. Ferreri AJ, Govi S, Ponzoni M. Marginal zone lymphomas and infectious agents. Semin Cancer Biol. 2013;23(6):431–440.

70. Ferreri AJ, Govi S, Pasini E, et al. Chlamydophila psittaci eradication with doxycycline as first-line targeted therapy for ocular adnexae lymphoma: final results of an international phase II trial. J Clin Oncol. 2012;30(24):2988–2994.

71. Thieblemont C, Berger F, Dumontet C, et al. Mucosa-associated lymphoid tissue lymphoma is a disseminated disease in one third of 158 patients analyzed. Blood. 2000;95(3):802–806.

72. Yahalom J. MALT lymphomas: a radiation oncology viewpoint. Ann Hematol. 2001;80(Suppl 3):B100–B105.

73. Koch P, Probst A, Berdel WE, et al. Treatment results in localized primary gastric lymphoma: data of patients registered within the German multicenter study (GIT NHL 02/96). J Clin Oncol. 2005;23(28):7050–7059.

74. Goda JS, Gospodarowicz M, Pintilie M, et al. Long-term outcome in localized extranodal mucosa-associated lymphoid tissue lymphomas treated with radiotherapy. Cancer. 2010;116(16):3815–3824.

75. Teckie S, Qi S, Lovie S, et al. Long-term outcomes and patterns of relapse of early-stage extranodal marginal zone lymphoma treated with radiation therapy with curative intent. Int J Radiat Oncol Biol Phys. 2015;92(1):130–137.

76. Wirth A, Gospodarowicz M, Aleman BM, et al. Long-term outcome for gastric marginal zone lymphoma treated with radiotherapy: a retrospective, multi-centre, International Extranodal Lymphoma Study Group study. Ann Oncol. 2013;24(5):1344–1351.

77. (NCCN). NCCN. National Comprehensive Cancer Network guidelines V.2.2013: non-Hodgkin’s lymphoma. National Comprehensive Cancer Network Guidelines; 2013. Available from: http://www.nccn.org/professionals/physician_gls/PDF/nhl.pdf. Accessed November 11, 2013.

78. Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381(9873):1203–1210.

79. Salar A, Domingo-Domenech E, Panizo C, et al. First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2014;1(3):e104–e111.

80. Zucca E, Conconi A, Martinelli G, et al. Final results of the IELSG-19 randomized trial of mucosa-associated lymphoid tissue lymphoma: improved event-free and progression-free survival with rituximab plus chlorambucil versus either chlorambucil or rituximab monotherapy. J Clin Oncol. 2017;35(17):1905–1912.

81. Thieblemont C, Felman P, Callet-Bauchu E, et al. Splenic marginal-zone lymphoma: a distinct clinical and pathological entity. Lancet Oncol. 2003;4(2):95–103.


Chacón JI, Mollejo M, Muñoz E, et al. Splenic marginal zone lymphoma: clinical characteristics and prognostic factors in a series of 60 patients. Blood. 2002;100(5):1648–1654.

83. Olszewski AJ. Survival outcomes with and without splenectomy in splenic marginal zone lymphoma. Am J Hematol. 2012;87(11): E119–E122.

84. Kalpadakis C, Pangalis GA, Angelopoulou MK, et al. Treatment of splenic marginal zone lymphoma with rituximab monotherapy: progress report and comparison with splenectomy. Oncologist. 2013; 18(2):190–197.

85. Lefrère F, Hermine O, Belanger C, et al. Fludarabine: an effective treatment in patients with splenic lymphoma with villous lymphocytes. Leukemia. 2000;14(4):573–575.

86. Kalpadakis C, Pangalis GA, Dimopoulou MN, et al. Rituximab monotherapy is highly effective in splenic marginal zone lymphoma. Hematol Oncol. 2007;25(3):127–131.

87. Arcaini L, Orlandi E, Scotti M, et al. Combination of rituximab, cyclophosphamide, and vincristine induces complete hematologic remission of splenic marginal zone lymphoma. Clin Lymphoma. 2004;4(4):250–252.

88. Iannitto E, Luminari S, Tripodo C, et al. Rituximab with cyclophosphamide, vincristine, non-pegylated liposomal doxorubicin and prednisone as first-line treatment for splenic marginal zone lymphoma: a Fondazione Italiana Linfomi phase II study. Leuk Lymphoma. 2015;56(12):3281–3287.

89. Lenglet J, Traullé C, Mounier N, et al. Long-term follow-up analysis of 100 patients with splenic marginal zone lymphoma treated with splenectomy as first-line treatment. Leuk Lymphoma. 2014;55(8):1854–1860.

90. Troussard X, Valensi F, Duchayne E, et al. Splenic lymphoma with villous lymphocytes: clinical presentation, biology and prognostic factors in a series of 100 patients. Groupe Francais d’Hématologie Cellulaire (GFHC). Br J Haematol. 1996;93(3):731–736.

91. Bennett M, Schechter GP. Treatment of splenic marginal zone lymphoma: splenectomy versus rituximab. Semin Hematol. 2010;47(2):143–147.

92. Kalpadakis C, Pangalis GA, Vassilakopoulos TP, Sachanas S, Angelopoulou MK. Treatment of splenic marginal zone lymphoma: should splenectomy be abandoned? Leuk Lymphoma. 2014;55(7):1463–1470.

93. Bennett M, Yegena S, Dave HP, Schechter GP. Re: rituximab monotherapy is highly effective in splenic marginal zone lymphoma. Hematol Oncol. 2008;26(2):114.

94. Else M, Marín-Niebla A, de la Cruz F, et al. Rituximab, used alone or in combination, is superior to other treatment modalities in splenic marginal zone lymphoma. Br J Haematol. 2012;159(3):322–328.

95. Brown JR, Friedberg JW, Feng Y, et al. A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. Br J Haematol. 2009;145(6):741–748.

96. Cervetti G, Galimberti S, Sordi E, et al. Significant efficacy of 2-CdA with or without rituximab in the treatment of splenic marginal zone lymphoma (SMZL). Ann Oncol. 2010;21(4):851–854.

97. Orciuolo E, Buda G, Sordi E, et al. 2CdA chemotherapy and rituximab in the treatment of marginal zone lymphoma. Leuk Res. 2010;34(2):184–189.

98. Laribi K, Tempescul A, Ghnaya H, et al. The bendamustine plus rituximab regimen is active against primary nodal marginal zone B-cell lymphoma. Hematol Oncol. 2016;35(4):536–541.

99. Thieblemont C, Coiffier B. Management of marginal zone lymphomas. Curr Treat Options Oncol. 2006;7(3):213–222.

100. Avivi I, Arcaini L, Ferretti V, et al. High dose therapy and autologous stem cell transplantation in marginal zone lymphoma: an EBMT-FIL-gimeto retrospective study. Blood. 2014;124:2526.

101. Bertoni F, Coiffier B, Salles G, et al. MALT lymphomas: pathogenesis can drive treatment. Oncology (Williston Park). 2011;25(12):1134–1142, 1147.

102. Li L, Bierman P, Vose J, Loberiza F, Armitage JO, Bociek RG. High-dose therapy/autologous hematopoietic stem cell transplantation in relapsed or refractory marginal zone non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2011;11(3):253–256.

103. Brown JR, Gaudet G, Friedberg JW, et al. Autologous bone marrow transplantation for marginal zone non-Hodgkin’s lymphoma. Leuk Lymphoma. 2004;45(2):315–320.

104. Locke FL, Neelapu SS, Bartlett NL, et al. Clinical and biologic covariates of outcomes in ZUMA-1: a pivotal trial of axicabtagene ciloleucel (axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (r-NHL). J Clin Oncol. 2017;35(15 Suppl):7512.

105. Gil L, Kazmierczak M, Kroll-Balcerzak R, Komarnicki M. Bendamustine-based therapy as first-line treatment for non-Hodgkin lymphoma. Med Oncol. 2014;31(5):944.

106. Kiesewetter B, Mayerhoefer ME, Lukas J, Zielinski CC, Müllauer L, Raderer M. Rituximab plus bendamustine is active in pretreated patients with extragastric marginal zone B cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma). Ann Hematol. 2014;93(2):249–253.

107. Conconi A, Martinelli G, Lopez-Guillermo A, et al. Clinical activity of bortezomib in relapsed/refractory MALT lymphomas: results of a phase II study of the International Extranodal Lymphoma Study Group (IELSG). Ann Oncol. 2011;22(3):689–695.

108. 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.

109. Kiesewetter B, Willenbacher E, Willenbacher W, et al. A phase II study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma). Blood. 2017;129(3):383–385.

110. Kalpadakis C, Pangalis GA, Angelopoulou MK, Vassilakopoulos TP. Treatment of splenic marginal zone lymphoma. Best Pract Res Clin Haematol. 2017;30(1–2):139–148.

111. Bennett M, Sharma K, Yegena S, Gavish I, Dave HP, Schechter GP. Rituximab monotherapy for splenic marginal zone lymphoma. Haematologica. 2005;90(6):856–858.

112. Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014;123(19):2944–2952.

113. Troch M, Jonak C, Müllauer L, et al. A phase II study of bortezomib in patients with MALT lymphoma. Haematologica. 2009;94(5):738–742.

114. O’Connor OA, Wright J, Moskowitz C, et al. Phase II clinical experience with the novel proteasome inhibitor bortezomib in patients with indolent non-Hodgkin’s lymphoma and mantle cell lymphoma. J Clin Oncol. 2005;23(4):676–684.

115. Zucca E, Bertoni F. The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance. Blood. 2016;127(17):2082–2092.

116. Thieblemont C, Cascione L, Conconi A, et al. A MALT lymphoma prognostic index. Blood. 2017;130(12):1409–1417.

117. Bertoni F, Zucca E. State-of-the-art therapeutics: marginal-zone lymphoma. J Clin Oncol. 2005;23(26):6415–6420.

118. Montalbán C, Abraira V, Arcaini L, et al. Risk stratification for Splenic Marginal Zone Lymphoma based on haemoglobin concentration, platelet count, high lactate dehydrogenase level and extrahilar lymphadenopathy: development and validation on 593 cases. Br J Haematol. 2012;159(2):164–171.

119. Montalban C, Abraira V, Arcaini L, et al. Simplification of risk stratification for splenic marginal zone lymphoma: a point-based score for practical use. Leuk Lymphoma. 2014;55(4):929–931.

120. Kuper-Hommel MJ, van de Schans SA, Vreugdenhil G, van Krieken JH, Coebergh JW. Trends in incidence, therapy and outcome of localized nodal and extranodal marginal zone lymphomas: declining incidence and inferior outcome for gastrointestinal sites. Leuk Lymphoma. 2013;54(9):1891–1897.

121. Berger F, Felman P, Thieblemont C, et al. Non-MALT marginal zone B-cell lymphomas: a description of clinical presentation and outcome in 124 patients. Blood. 2000;95(6):1950–1956.

122. Heilgeist A, McClanahan F, Ho AD, Witzens-Harig M. Prognostic value of the Follicular Lymphoma International Prognostic Index score in marginal zone lymphoma: an analysis of clinical presentation and outcome in 144 patients. Cancer. 2013;119(1):99–106.

123. Bernard S, Danglade D, Gardano L, et al. Inhibitors of BCR signalling interrupt the survival signal mediated by the micro-environment in mantle cell lymphoma. Int J Cancer. 2015;136(12):2761–2774.

124. de Gorter DJ, Beuling EA, Kersseboom R, et al. Bruton’s tyrosine kinase and phospholipase Cgamma2 mediate chemokine-controlled B cell migration and homing. Immunity. 2007;26(1):93–104.

125. de Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119(11):2590–2594.

126. Ponader S, Chen SS, Buggy JJ, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119(5):1182–1189.

127. 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.

128. Bartlett NL, Costello BA, LaPlant BR, et al. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2017;131(2):182–190.

129. Fowler N, Nastoupil L, de Vos S, et al. Ibrutinib plus rituximab in treatment-naive patients with follicular lymphoma: results from a multicenter, phase 2 study. Blood. 2015;126(23):470.

130. Fowler NH. A phase 3 study of ibrutinib in combination with either bendamustine and rituximab (BR) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously treated follicular lymphoma or marginal zone lymphoma. In: Hiddemann W, editors. Vol 32. 2014 ASCO Annual Meeting. J Clin Oncol. 2014:32.

131. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014; 370(12):1101–1110.

132. Sehn LH, Chua N, Mayer J, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016;17(8):1081–1093.

133. Herold M, Hoster E, Janssens A, et al. Immunochemotherapy with obinutuzumab or rituximab in a subset of patients in the randomised gallium trial with previously untreated marginal zone lymphoma (MZL). Hematol Oncol. 2017;35:146–147.