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Low-Grade Lymphomas (Other than CLL/SLL) in Older Patients

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Geriatric Oncology

Abstract

The incidence of non-Hodgkin lymphomas has been progressively increasing over the last decades, especially in the elderly. Taken with an aging population, this scenario represents a growing health problem with significant implications for the care of older patients. In fact, because of comorbidities and organ dysfunctions, elderly patients are at an increased risk of therapy-related toxicity. In the setting of indolent lymphomas, even in advanced stages, there is no benefit in terms of outcome in administering early therapy. On the contrary, a “watch and wait” approach represents the standard of care, until specific treatment is indicated. In this case, an accurate evaluation could be made by the comprehensive geriatric assessment (CGA) based on age, comorbidities, and functional disabilities of daily living, which is an important tool to discriminate between fit, unfit, and frail patients. CGA is useful to determine the patient chance of tolerating and responding to therapy, making a whole evaluation of older patients, beyond chronological age itself. The therapeutic goal for elderly patients is to find a balance between effective therapy and related toxicity; therefore, therapy regimens used for younger patients may not be always appropriate for the elderly. When treatment is indicated and feasible, the use of rituximab in combination with chemotherapy is the standard of care in first-line treatment. Furthermore, there is a remarkable number of emerging new drugs which represent valid therapeutic options in relapsed/refractory setting and may allow a chemo-free treatment; therefore, continued participation in clinical trials which include also elderly patients should be recommended.

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References

  • Arcaini L, Lazzarino M, Colombo N, Intergruppo Italiano Linfomi, et al. Splenic marginal zone lymphoma: a prognostic model for clinical use. Blood. 2006;107(12):4643–9.

    Article  CAS  PubMed  Google Scholar 

  • 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):346–50.

    Article  CAS  PubMed  Google Scholar 

  • 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):1404–10.

    Article  CAS  PubMed  Google Scholar 

  • Arcaini L, Besson K, 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. Blood. 2015;126:3938.

    Google Scholar 

  • Arcaini L, Rossi D, Paulli M. Splenic marginal zone lymphoma: from genetics to management. Blood. 2016;127(17):2072–81.

    Article  CAS  PubMed  Google Scholar 

  • Ardeshna KM, Smith P, Norton A, et al. Long-term effect of watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomized controlled trial. Lancet. 2003;362(9383):516–22.

    Article  CAS  PubMed  Google Scholar 

  • Ardeshna KM, Qian W, Smith P. An intergroup randomized trial of rituximab versus watch and wait strategy in patients with stage II, III, IV, asymptomatic, non bulky follicular lymphoma (grades 1, 2, 3a), a preliminary analysis. Blood. 2010;116:6.

    Google Scholar 

  • Bai L-Y, Yang M-H, Chiou T-J, et al. Non Hodgkin Lymphoma in elderly patients. Cancer. 2003;98:1188. American Cancer Society.

    Article  PubMed  Google Scholar 

  • Bairey O, Benjamini O, Blickstein D, et al. Non-Hodgkin’s Lymphoma in patients 80 years of age or older. Ann Oncol. 2006;17:928–34.

    Article  CAS  PubMed  Google Scholar 

  • Barrington SF, Mikhaeel NG, Kostakoglu L, et al. Role of imaging in the staging and response assessment of lymphoma: consensus of the international conference on malignant lymphomas imaging working group. J Clin Oncol. 2014;32:3048–58.

    Article  PubMed  PubMed Central  Google Scholar 

  • Berkman B, Rohan B, Sampson S. Myths and biases related to cancer in the elderly. Cancer. 1994;74(7 Suppl):2004–8.

    Article  CAS  PubMed  Google Scholar 

  • Buske C, Leblond V, Dimopoulos E, et al. Waldenstrom’s Macroglobulinemia: ESMO clinical practice guidelines. Ann Oncol. 2013;24(Suppl 6):vi155–9.

    Article  PubMed  Google Scholar 

  • Caimi PF, Barr PM, Berger NA, Lazarus HM. Non-Hodgkin Lymphoma in the elderly. Drugs Aging. 2010;27(3):211–38.

    Article  PubMed  Google Scholar 

  • Castellino A, Santambrogio E, Nicolosi M, et al. Follicular lymphoma: the management of the elderly. Mediterranean J Hematol Infect Dis. 2017;9:e2017009.

    Article  Google Scholar 

  • Chen Q, Ayer T, Nastoupil LJ, et al. Initial management strategies for follicular lymphoma. Int J Hematol Oncol. 2012;1(1):35–45.

    Article  CAS  PubMed  Google Scholar 

  • Cheson BD, Fisher R, Barrington S, et al. Recommendations for Initial Evaluation, staging and response assessment of Hodgkin and non-Hodgkin Lymphoma: the Lugano Classification. J Clin Oncol. 2014;32: 3059–67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Conconi A, Franceshetti S, Aprile von Hohenstaufen K, et al. Histologic transformation in marginal zone lymphomas. Ann Oncol. 2015;26(11):2329–35.

    Article  CAS  PubMed  Google Scholar 

  • Cutter J, Wallenstein S, Troy K. Non-Hodgkin’s Lymphoma in patients 70 years of age or older: factors associated with survival. Leukemia Res. 2002;26:447–50.

    Article  Google Scholar 

  • Dimopoulos MA, on behalf of the iNNOVATE Study Group and the European Consortium for Waldenström’s Macroglobulinemia, et al. Ibrutinib for patients with rituximab-refractory Waldenström’s macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial. Lancet Oncol. 2017;18(2):241–50.

    Article  CAS  PubMed  Google Scholar 

  • Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, et al. Primary treatment of Waldenstrom macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol. 2007;25(22):3344–9.

    Article  CAS  PubMed  Google Scholar 

  • 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;24:857e77.

    Article  Google Scholar 

  • Dreyling M, Ghielmini S, Rule S, et al. Newly diagnosed and relapsed follicular lymphoma: ESMO clinical practice guidelines. Ann Oncol. 2016;27(suppl 5):v83–90.

    Article  CAS  PubMed  Google Scholar 

  • Else M, Marin-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):322–8.

    Article  CAS  PubMed  Google Scholar 

  • Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;10:1824–31.

    Article  Google Scholar 

  • Extermann M, Overcash J, Lyman GH, et al. Comorbidity and functional status are independent in older cancer patients. J Clin Oncol. 1998;16:1582–7.

    Article  CAS  PubMed  Google Scholar 

  • Federico M, Bellei M, Marcheselli L, et al. Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol. 2009;27:4555–62.

    Article  PubMed  Google Scholar 

  • 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. 2012a;30:2988–94.

    Article  CAS  PubMed  Google Scholar 

  • Ferreri AJ, Govi S, Raderer M, et al. Helicobacter pylori eradication as exclusive treatment for limited-stage gastric diffuse large B-cell lymphoma: results of a multicenter phase 2 trial. Blood. 2012b;120(18): 3858–60.

    Google Scholar 

  • 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):2944–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fowler NH, Davis RE, Rawal S. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014;15:1311–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ganai S, Lee KF, Merrill A, et al. Adverse outcomes of geriatric patients undergoing abdominal surgery who are at high risk for delirium. Arch Surg. 2007;142:1072e8.

    Article  Google Scholar 

  • Gertz MA, Kyle RA. Hyperviscosity syndrome. J Intensive Care Med. 1995;10:128–41.

    Article  CAS  PubMed  Google Scholar 

  • Goede V. Marginal zone lymphoma in elderly and geriatric patients. Best Pract Res Clin Hematol. 2017;30: 156–65.

    Article  Google Scholar 

  • Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the international lymphoma study group. Blood. 1994;84:1361–92.

    PubMed  CAS  Google Scholar 

  • Hiddemann W, Kneba M. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood. 2005;106(12):3725–32.

    Article  CAS  PubMed  Google Scholar 

  • Kalpadakis C, Pangalis GA, Angelopoulou MK, et al. Validation of the simplified prognostic score for splenic marginal zone lymphoma of the splenic marginal zone lymphoma working group. Leuk Lymphoma. 2014;55(11):2640–2.

    Article  PubMed  Google Scholar 

  • Kavic SM, Segan RD, Park AE. Laparoscopic splenectomy in the elderly: a morbid procedure? Surg Endosc. 2005;19:1561e4.

    Article  Google Scholar 

  • Leblond V, Johnson S, Chevret S, et al. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated Waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013;31:301e7.

    Article  CAS  Google Scholar 

  • Martinelli G, Laszlo D, Bertolini F, et al. Chlorambucil in combination with induction and maintenance rituximab is feasible and active in indolent Non-Hodgkin’s Lymphoma. Br J Haematol. 2003;123(2):271–7.

    Article  CAS  PubMed  Google Scholar 

  • Matsuo K, Kusano A, Sugumar A, et al. Effect of hepatitis C virus infection on the risk of Non-Hodgkin’s Lymphoma: a meta-analysis of epidemiological studies. Cancer Sci. 2004;95:745–52.

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin P, Hagemeister FB, Rodriguez MA, et al. Safety of fludarabine, mitoxantrone, and dexamethasone combined with rituximab in the treatment of stage IV indolent lymphoma. Semin Oncol. 2000;27:37–41.

    PubMed  CAS  Google Scholar 

  • Montalban C, Abraira V, Arcaini L, Splenic Marginal Zone Lymphoma Study Group, 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):164–71.

    Article  PubMed  Google Scholar 

  • Montalban C, Abraira V, Arcaini L, Splenic Marginal Zone Lymphoma Study Group (SMZLSG), et al. Simplification of risk stratification for splenic marginal zone lymphoma: a point-based score for practical use. Leuk Lymphoma. 2014;55(4):929–31.

    Article  PubMed  Google Scholar 

  • Morrison VA. Non-Hodgkin’s Lymphoma in the elderly; review article, published on Cancer network. 2007.

    Google Scholar 

  • Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with Yttrium-90–Ibritumomab Tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol. 2008;26(32): 5156–64.

    Article  CAS  PubMed  Google Scholar 

  • Ninan MJ, Morrison VA. Therapeutic approaches to Non-Hodgkin’s Lymphoma in the elderly patient. Expert Rev Hematol. 2009;2(2):173–82.

    Article  PubMed  Google Scholar 

  • Older Adults Oncology. National comprehensive cancer network (NCCN) clinical practice guidelines in oncology; 2017. Version 2. J Natl Compr Canc Netw. 2014;12(9):1282–303.

    Google Scholar 

  • Olszewski AJ, Castillo JJ. Survival of patients with marginal zone lymphoma: analysis of the surveillance, epidemiology and end results database. Cancer. 2013;119(3):629–38.

    Article  PubMed  Google Scholar 

  • Peterson PM, Goapodarowitz M, Tsang R, et al. Long-term outcome in stage I and II follicular lymphoma following treatment with involved field radiotherapy alone. Proc ASCO. 2004;23:561.

    Google Scholar 

  • Radford J, Davies A, Cartron G, et al. Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study BO21000. Blood. 2013;122(7):1137–43. https://doi.org/10.1182/blood-2013-01-481341.

    Article  PubMed  CAS  Google Scholar 

  • Rahman AM, Yusuf SW, Ewer MS. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomedicine. 2007;2(4): 567–83.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Rummel MJ. Bendamustine plus rituximab versus CHOP plus rituximab in the first-line treatment of patients with Waldenström’s disease – first interim results of a randomized phase III study of the Studygroup Indolent Lymphomas (StiL). In: Vth international Workshop on Waldenström Macroglobulinemia. Stockholm; 2008.

    Google Scholar 

  • Rummel MJ, Al-Batran SE, Kim SZ, et al. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade Non-Hodgkin’s Lymphoma. J Clin Oncol. 2005;23(15):3383–9.

    Article  CAS  PubMed  Google Scholar 

  • Rummel MJ, Niederle N, Maschmeyer G, Study Group Indolent Lymphomas (StiL), 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):1203–10.

    Article  CAS  PubMed  Google Scholar 

  • Saadoun D, Suarez F, Lefrere F, et al. Splenic lymphoma with villous lymphocytes, associated with type II cryoglobulinemia and HCV infection: a new entity? Blood. 2005;105(1):74–6.

    Article  CAS  PubMed  Google Scholar 

  • Sagaert X, de Paepe P, Libbrecht L, et al. Forkhead box protein P1 expression in mucosa associated lymphoid tissue lymphomas predicts poor prognosis and transformation to diffuse large B-cell lymphoma. J Clin Oncol. 2006;24(16):2490–7.

    Article  CAS  PubMed  Google Scholar 

  • Salles G, Seymour JF, Offner F, et al. Rituximab maintenance for 2 years in patients with high tumor burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomized controlled trial. Lancet. 2011;377(9759):42–51.

    Article  CAS  PubMed  Google Scholar 

  • Schulz H, Bohlius J, Skoetz N, et al. Chemotherapy plus rituximab versus chemotherapy alone for B-cell non-Hodgkin’s Lymphoma. Cochrane Database Syst Rev. 2007;4:CD003805.

    Google Scholar 

  • 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;17:1081.

    Article  CAS  PubMed  Google Scholar 

  • Seymour JF, Feugier P, Offner F, et al. Updated 6 year follow-up of the PRIMA study confirms the benefit of 2-year rituximab maintenance in follicular lymphoma patients responding to frontline Immunochemotherapy. Blood. 2013;122:abstr.509.

    Google Scholar 

  • Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by sub-type: a report from the Haematological malignancy research network. Br J Cancer. 2011;105:1684–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solal-Céligny P, Roy P, Colombat P, White J, Armitage JO, et al. Follicular lymphoma international prognostic index. Blood. 2004;104:1258–65.

    Article  CAS  PubMed  Google Scholar 

  • 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):3034–44.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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, non follicular B-cell lymphoma (marginal zone, lymphoplasmacytic, and small lymphocytic lymphoma). Clin Lymphoma Myeloma Leuk. 2015;15(2): 75–85.

    Article  PubMed  Google Scholar 

  • Taverna CJ, Martinell G, Hitz F, et al. Rituximab maintenance treatment for a maximum of 5 years in follicular lymphoma: results of the randomized phase III trial SAKK 35/03. J Clin Oncol. 2013;122:abstr.508.

    Google Scholar 

  • The Non-Hodgkin’s Lymphoma Classification Project. Effect of age on the characteristics and clinical behavior of Non-Hodgkin’s Lymphoma patients. Ann Oncol. 1997;8:973–8.

    Article  Google Scholar 

  • 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):41–7.

    Article  PubMed  Google Scholar 

  • Thieblemont C, Molina T and Davi F. Optimizing therapy for nodal marginal zone lymphoma. Blood. 2016;127:2064–2071.

    Article  CAS  PubMed  Google Scholar 

  • Trebouet A, Marchand T, Lemal R, et al. Lymphoma occurring in patients over 90 years of age characteristics, outcomes, and prognostic factors. A retrospective analysis of 234 cases from the LYSA. Ann Oncol. 2013;24:2612–8.

    Article  CAS  PubMed  Google Scholar 

  • Treon SP. How I treat Waldenstrom Macroglobulinemia. Blood. 2015;126:721–32.

    Article  CAS  PubMed  Google Scholar 

  • Treon SP, Branagan AR, Hunter Z, et al. Paradoxical increases in serum IgM and viscosity levels following rituximab in Waldenstrom’s macroglobulinemia. Ann Oncol. 2004;15(10):1481–3.

    Article  CAS  PubMed  Google Scholar 

  • Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med. 2012;367:826–33.

    Article  CAS  PubMed  Google Scholar 

  • Treon SP, Tripsas CK, Meid K, et al. Ibrutinib in previously treated Waldenstrom’s macroglobulinemia. N Engl J Med. 2015;372:1430–40.

    Article  CAS  PubMed  Google Scholar 

  • Tucci A, Ferrari S, Bottelli C, et al. A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer. 2009;115:4547–53.

    Article  PubMed  Google Scholar 

  • Tucci A, Martelli M, Rigacci L, et al. Comprehensive geriatric assessment is an essential tool to support treatment decisions in elderly patients with diffuse large B-cell lymphoma: a prospective multicenter evaluation in 173 patients by the Lymphoma Italian Foundation (FIL). Leuk Lymphoma. 2015;56(4):921–6.

    Article  CAS  PubMed  Google Scholar 

  • Viardot A, Buske C. Indolent lymphomas in older patients. In: Management of hematological cancer in older people. London: Springer; 2015.

    Google Scholar 

  • Vitolo U, Ladetto M, Boccomini C, et al. Rituximab maintenance compared with observation after brief first-line R-FND chemoimmunotherapy with rituximab consolidation in patients age older than 60 years with advanced follicular lymphoma: a phase III randomized study by the Fondazione Italiana Linfomi. J Clin Oncol. 2013;31(27):3351–9.

    Article  CAS  PubMed  Google Scholar 

  • Zelenetz AD, Gordon LI, Wierda WG, et al. Non-Hodgkin’s Lymphomas. In: National comprehensive cancer network (NCCN) clinical practice guidelines in oncology; 2014. Version 4.

    Google Scholar 

  • Zucca E, Bertoni F. The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance. Blood. 2016;127(17):2082–92.

    Article  CAS  PubMed  Google Scholar 

  • Zucca E, Conconi A, Pedrinis E, et al. Non gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. Blood. 2003;101:2489–95.

    Article  CAS  PubMed  Google Scholar 

  • 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):vi144–8.

    PubMed  Google Scholar 

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Defrancesco, I., Frigeni, M., Arcaini, L. (2018). Low-Grade Lymphomas (Other than CLL/SLL) in Older Patients. In: Extermann, M. (eds) Geriatric Oncology . Springer, Cham. https://doi.org/10.1007/978-3-319-44870-1_41-1

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