Skip to main content

Advertisement

SpringerLink
Log in

Follicular Lymphoma: Past, Present, and Future

  • Lymphoma (DO Persky, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Even in the modern era, follicular lymphoma (FL) remains largely an incurable but treatable disease with both standard and novel treatment modalities. Despite the abundance of efficacious treatment modalities currently available, there is no universally agreed upon standard approach to treatment for patients with FL, particularly in the relapsed/refractory (R/R) setting. There is an increasing need for better tools to risk-stratify patients and to identify those likely to experience relapse early. Additionally, the use of gene expression profiling and next-generation sequencing techniques in recent years has led to a wealth of knowledge regarding the molecular drivers of lymphomagenesis; however, much of this knowledge is not currently applicable on a day to day basis in the clinic setting. Further studies are needed to determine a validated, clinically relevant predictive model that incorporates patient factors and molecular factors that will guide clinicians on the most effective treatment strategy. With many questions left unanswered, it is our opinion that the treatment of FL and sequencing of therapy in the R/R setting should be a personalized approach that balances patient-specific factors such as preferences and comorbidities with treatment-related factors such as known response rates and toxicity profiles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Casulo C, Nastoupil L, Fowler NH, Friedberg JW, Flowers CR. Unmet needs in the first-line treatment of follicular lymphoma. Ann. Oncol. 2017;28(9):2094–106.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  2. Teras LR, DeSantis CE, Cerhan JR, Morton LM, Jemal A, Flowers CR. 2016 US lymphoid malignancy statistics by World Health Organization subtypes. CA Cancer J Clin. 2016;

  3. Nastoupil LJ, Sinha R, Byrtek M, Ziemiecki R, Taylor M, Friedberg JW, et al. Comparison of the effectiveness of frontline chemoimmunotherapy regimens for follicular lymphoma used in the United States. Leuk Lymphoma. 2015;56(5):1295–302.

    Article  PubMed  CAS  Google Scholar 

  4. •• Casulo C, Byrtek M, Dawson KL, Zhou X, Farber CM, Flowers CR, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J Clin Oncol. 2015;33(23):2516–22. Identified relapse within 2 years as a high-risk feature in FL.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Cheah CY, Fowler NH. Novel agents for relapsed and refractory follicular lymphoma. Best Pract Res Clin Haematol. 2018;31(1):41–8.

    Article  PubMed  Google Scholar 

  6. Reagan PM, Friedberg JW. Follicular lymphoma: first-line treatment without chemotherapy for follicular lymphoma. Curr Treat Options in Oncol. 2015;16(7):32.

    Article  Google Scholar 

  7. Hiddemann W, Cheson BD. How we manage follicular lymphoma. Leukemia. 2014;28(7):1388–95.

    Article  PubMed  CAS  Google Scholar 

  8. •• Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM, Szczepanowski M, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015;16(9):1111–22. Development of the m7-FLIPI as a clinicomolecular prognostic tool in FL.

    Article  PubMed  CAS  Google Scholar 

  9. Buske C, Hoster E, Dreyling M, Hasford J, Unterhalt M, Hiddemann W. The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome. Blood. 2006;108(5):1504–8.

    Article  PubMed  CAS  Google Scholar 

  10. Solal-Celigny P, Roy P, Colombat P, White J, Armitage JO, Arranz-Saez R, et al. Follicular lymphoma international prognostic index. Blood. 2004;104(5):1258–65.

    Article  PubMed  CAS  Google Scholar 

  11. Federico M, Bellei M, Marcheselli L, Luminari S, Lopez-Guillermo A, Vitolo U, 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(27):4555–62.

    Article  PubMed  Google Scholar 

  12. Lopez-Guillermo A. A novel clinicogenetic prognostic score for follicular lymphoma. Lancet Oncol. 2015;16(9):1011–2.

    Article  PubMed  Google Scholar 

  13. Kahl BS. Follicular lymphoma: are we ready for a risk-adapted approach? Hematology Am Soc Hematol Educ Program. 2017;2017(1):358–64.

    PubMed  Google Scholar 

  14. Andorsky DJ, Yacoub A, Melear JM, Coleman M, Kolibaba KS, Brooks HD, et al. Phase IIIb randomized study of lenalidomide plus rituximab (R2) followed by maintenance in relapsed/refractory NHL: analysis of patients with double-refractory or early relapsed follicular lymphoma (FL). J Clin Oncol. 2017;35(15_suppl):7502.

    Article  Google Scholar 

  15. Huet S, Tesson B, Jais JP, Feldman AL, Magnano L, Thomas E, et al. A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts. Lancet Oncol. 2018;19(4):549–61.

    Article  PubMed  Google Scholar 

  16. Mac Manus MP, Hoppe RT. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J. Clin Oncol. 1996;14(4):1282–1290.

  17. Nastoupil L, Sinha R, Hirschey A, Flowers CR. Considerations in the initial management of follicular lymphoma. Community Oncol. 2012;9(11):S53–60.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Brice P, Bastion Y, Lepage E, Brousse N, Haioun C, Moreau P, et al. Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: a randomized study from the Groupe d’Etude des Lymphomes Folliculaires. Groupe d’Etude des Lymphomes de l'Adulte. J. Clin Oncol. 1997;15(3):1110–7.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  20. Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P, et al. Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. J. Clin Oncol. 2014;15(4):424–35.

    CAS  Google Scholar 

  21. Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, et al. Rituximab extended schedule or re-treatment trial for low-tumor burden follicular lymphoma: eastern cooperative oncology group protocol e4402. J Clin Oncol. 2014;32(28):3096–102.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Friedberg JW, Taylor MD, Cerhan JR, Flowers CR, Dillon H, Farber CM, et al. Follicular lymphoma in the United States: first report of the national LymphoCare study. J Clin Oncol: official journal of the American Society of Clinical Oncology. 2009;27(8):1202–8.

    Article  Google Scholar 

  23. Hiddemann W, Kneba M, Dreyling M, Schmitz N, Lengfelder E, Schmits R, et al. 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  PubMed  CAS  Google Scholar 

  24. Marcus R, Imrie K, Belch A, Cunningham D, Flores E, Catalano J, et al. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood. 2005;105(4):1417–23.

    Article  PubMed  CAS  Google Scholar 

  25. Herold M, Haas A, Srock S, Neser S, Al-Ali KH, Neubauer A, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol. 2007;25(15):1986–92.

    Article  PubMed  CAS  Google Scholar 

  26. Salles G, Mounier N, de Guibert S, Morschhauser F, Doyen C, Rossi JF, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 2008;112(13):4824–31.

    Article  PubMed  CAS  Google Scholar 

  27. Marcus R, Imrie K, Solal-Celigny P, Catalano JV, Dmoszynska A, Raposo JC, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol. 2008;26(28):4579–86.

    Article  PubMed  CAS  Google Scholar 

  28. Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C, 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  PubMed  CAS  Google Scholar 

  29. •• Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, et al. Obinutuzumab for the First-Line Treatment of Follicular Lymphoma. N Engl J Med. 2017;377(14):1331–44. GALLIUM trial. Results led to FDA approval of obinutuzumab in combination with chemotherapy followed by maintenance obinutuzumab.

    Article  PubMed  CAS  Google Scholar 

  30. Han TT, Fan L, Li JY, Xu W. Role of chemokines and their receptors in chronic lymphocytic leukemia: function in microenvironment and targeted therapy. Cancer Biol Ther. 2014;15(1):3–9.

    Article  PubMed  CAS  Google Scholar 

  31. Fowler NH, Cheah CY, Gascoyne RD, Gribben J, Neelapu SS, Ghia P, et al. Role of the tumor microenvironment in mature B-cell lymphoid malignancies. Haematologica. 2016;101(5):531–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, et al. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014;15(12):1311–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Becnel MR, Nastoupil L, Davis RE, Hagemeister FB, Fanale MA, Fayad L, et al. Safety and activity of lenalidomide and rituximab in previously untreated marginal zone lymphoma: subgroup analysis and long-term follow-up of an open-label phase II trial. Blood. 2017;130(Suppl 1):4040.

    Google Scholar 

  34. Jerkeman M, Hallek M, Dreyling M, Thieblemont C, Kimby E, Staudt L. Targeting of B-cell receptor signalling in B-cell malignancies. J Intern Med. 2017;282:415–28.

    Article  PubMed  CAS  Google Scholar 

  35. Rosenquist R, Bea S, Du MQ, Nadel B, Pan-Hammarstrom Q. Genetic landscape and deregulated pathways in B-cell lymphoid malignancies. J Intern Med. 2017;282:371–94.

    Article  PubMed  CAS  Google Scholar 

  36. Chen SS, Chang BY, Chang S, Tong T, Ham S, Sherry B, et al. BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia. Leukemia. 2016;30(4):833–43.

    Article  PubMed  CAS  Google Scholar 

  37. Spina V, Rossi D. Molecular pathogenesis of splenic and nodal marginal zone lymphoma. Best Pract Res Clin Haematol. 2017;30(1–2):5–12.

    Article  PubMed  Google Scholar 

  38. Barbieri F, Bajetto A, Thellung S, Wurth R, Florio T. Drug design strategies focusing on the CXCR4/CXCR7/CXCL12 pathway in leukemia and lymphoma. Expert Opin Drug Discovery. 2016;11(11):1093–109.

    Article  CAS  Google Scholar 

  39. Chen J, Kinoshita T, Sukbuntherng J, Chang BY, Elias L. Ibrutinib inhibits ERBB receptor tyrosine kinases and HER2-amplified breast cancer cell growth. Mol Cancer Ther. 2016;15(12):2835–44.

    Article  PubMed  CAS  Google Scholar 

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

  41. Salles G, Seymour JF, Offner F, Lopez-Guillermo A, Belada D, Xerri L, et al. Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet. 2011;377(9759):42–51.

    Article  PubMed  CAS  Google Scholar 

  42. • Salles GA, Seymour JF, Feugier P, Offner F, Lopez-Guillermo A, Belada D, et al. Long term follow-up of the PRIMA study: half of patients receiving rituximab maintenance remain progression free at 10 years. Blood. 2017;130(Suppl 1):486. Follow-up of PRIMA study suggesting durable remission with RM.

    Google Scholar 

  43. Hill BT, Nastoupil L, Winter AM, Becnel MR, Cerhan JR, Habermann TM, et al. Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab (BR) for follicular lymphoma: a real world analysis across 13 US cancer centers. Blood. 2017;130(Suppl 1):2779.

    Google Scholar 

  44. Trotman J, Fournier M, Lamy T, Seymour JF, Sonet A, Janikova A, et al. Positron emission tomography-computed tomography (PET-CT) after induction therapy is highly predictive of patient outcome in follicular lymphoma: analysis of PET-CT in a subset of PRIMA trial participants. J Clin Oncol. 2011;29(23):3194–200.

    Article  PubMed  Google Scholar 

  45. Trotman J, Luminari S, Boussetta S, Versari A, Dupuis J, Tychyj C, et al. Prognostic value of PET-CT after first-line therapy in patients with follicular lymphoma: a pooled analysis of central scan review in three multicentre studies. Lancel Haematol. 2014;1(1):e17–27.

    Article  Google Scholar 

  46. de Jong D, de Boer JP. Predicting transformation in follicular lymphoma. Leuk Lymphoma. 2009;50(9):1406–11.

    Article  PubMed  CAS  Google Scholar 

  47. • Cheson BD, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, et al. Overall survival benefit in patients with rituximab-refractory indolent non-Hodgkin lymphoma who received obinutuzumab plus bendamustine induction and obinutuzumab maintenance in the GADOLIN study. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018:Jco2017763656. RM following frontline BR is most impactful in patients that fail to achieve a CR at the end of induction.

  48. Witzig TE, Nowakowski GS, Habermann TM, Goy A, Hernandez-Ilizaliturri FJ, Chiappella A, et al. A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma. Ann Oncol. 2015;26(8):1667–77.

    Article  PubMed  CAS  Google Scholar 

  49. Witzig TE, Wiernik PH, Moore T, Reeder C, Cole C, Justice G, et al. Lenalidomide oral monotherapy produces durable responses in relapsed or refractory indolent non-Hodgkin’s lymphoma. J Clin Oncol. 2009;27(32):5404–9.

    Article  PubMed  CAS  Google Scholar 

  50. Leonard J, Gribben JG, Trněný M, Scheinberg P, Tobinai K, Fowler NH, et al. AUGMENT: a randomized, phase 3 trial in patients with relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) to compare efficacy and safety of lenalidomide plus rituximab (R2) versus placebo plus rituximab. J Clin Oncol. 2015;33(15_suppl):TPS8603-TPS.

    Google Scholar 

  51. Coleman M, Andorsky DJ, Yacoub A, Melear JM, Kolibaba KS, Brooks HD, et al. Phase IIIb study of lenalidomide plus rituximab followed by maintenance in relapsed or refractory NHL: analysis of marginal zone lymphoma. Hematol Oncol (ICML meeting). 2017;35(suppl S2):148. (Abstract 39)

    Article  Google Scholar 

  52. Bartlett NL, Costello BA, LaPlant BR, Ansell SM, Kuruvilla JG, Reeder CB, et al. Single-agent ibrutinib in relapsed or refractory follicular lymphoma: a phase 2 consortium trial. Blood. 2018;131(2):182–90.

    Article  PubMed  CAS  Google Scholar 

  53. Fowler NH, Hiddemann W, Leonard J, Larsen JS, Rose E, Zhuang SH, et al. A phase III 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. J Clin Oncol. 2015;33(15_suppl):TPS8601-TPS.

    Google Scholar 

  54. Davies A. Idelalisib for relapsed/refractory indolent B-cell non-Hodgkin’s lymphoma: an overview of pharmacokinetics and clinical trial outcomes. Expert Rev Hematol. 2015;8(5):581–93.

    Article  PubMed  CAS  Google Scholar 

  55. •• Dreyling M, Santoro A, Mollica L, Leppa S, Follows GA, Lenz G, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J. Clin Oncol. 2017;35(35):3898–905. Phase II trial of copanlisib that led to FDA approval in R/R FL.

    Article  PubMed  Google Scholar 

  56. Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, et al. PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008–18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Fowler N, Davis E. Targeting B-cell receptor signaling: changing the paradigm. Hematology Am Soc Hematol Educ Program. 2013;2013:553–60.

    PubMed  Google Scholar 

  58. • Gopal AK, Kahl BS, Flowers CR, Martin P, Ansell SM, Abella-Dominicis E, et al. Idelalisib is effective in patients with high-risk follicular lymphoma and early relapse after initial chemoimmunotherapy. Blood. 2017;129(22):3037–9. Idelalisib effective in patients with early relapse (within 2 years).

    Article  PubMed  CAS  Google Scholar 

  59. Greenwell IB, Ip A, Cohen JB. PI3K Inhibitors: Understanding toxicity mechanisms and management. Oncology (Williston Park, NY.). 2017;31(11):821–8.

    Google Scholar 

  60. Zelenetz AD, Barrientos JC, Brown JR, Coiffier B, Delgado J, Egyed M, et al. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017;18(3):297–311.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Davids MS, Roberts AW, Seymour JF, Pagel JM, Kahl BS, Wierda WG, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J. Clin Oncol. 2017;35(8):826–33.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Khan N, Kahl B. Targeting BCL-2 in hematologic malignancies. Target Oncol. 2018;

  63. Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, et al. A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica. 2015;100(3):357–62.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, 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):1198–203.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Evens AM, Balasubramanian S, Vose JM, Harb W, Gordon LI, Langdon R, et al. A phase I/II multicenter, open-label study of the oral histone deacetylase inhibitor abexinostat in relapsed/refractory lymphoma. Clin Cancer Res. 2016;22(5):1059–66.

    Article  PubMed  CAS  Google Scholar 

  66. Ribrag V, Kim WS, Bouabdallah R, Lim ST, Coiffier B, Illes A, et al. Safety and efficacy of abexinostat, a pan-histone deacetylase inhibitor, in non-Hodgkin lymphoma and chronic lymphocytic leukemia: results of a phase II study. Haematologica. 2017;102(5):903–9.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Korfi K, Ali S, Heward JA, Fitzgibbon J. Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations. Epigenetics. 2017;12(5):370–7.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Gulati N, Beguelin W, Giulino-Roth L. Enhancer of zeste homolog 2 (EZH2) inhibitors. Leukemia & Lymphoma. 2018:1–12.

  69. •• Morschhauser F, Salles G, McKay P, Tilly H, Schmitt A, Gerecitano J, et al. Interim report from a phase 2 multicenter study of tazemetostat, an EZH2 inhibitor, in patients with relapsed or refractory B-cell non-Hodgkin lymphomas. Haematol Oncol. 2017;35(S2):24–5. Led to FDA Fast Track Designation in R/R FL.

    Article  Google Scholar 

  70. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677–704.

    Article  PubMed  CAS  Google Scholar 

  71. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8(6):467–77.

    Article  PubMed  CAS  Google Scholar 

  72. Oncale M, Maymani H, Nastoupil L. Harnessing the immune system through programmed death-1 blockade in the management of Hodgkin lymphoma 2017. 1–7 p.

  73. Nastoupil LJ, Neelapu SS. Novel immunologic approaches in lymphoma: unleashing the brakes on the immune system. Curr Oncol Rep. 2015;17(7):30.

    Article  PubMed  CAS  Google Scholar 

  74. Nattamai D, Neelapu SS. PD-1 expression is markedly upregulated on intratumoral CD4+ and CD8+ T cells in follicular lymphoma and is associated with T-cell exhaustion. Blood. 2007;110(11):2749.

    Google Scholar 

  75. Nastoupil L, Westin JR, Fowler NH, Fanale MA, Samaniego F, Oki Y, et al. High complete response rates with pembrolizumab in combination with rituximab in patients with relapsed follicular lymphoma: results of an open-label, phase II study. Blood. 2017;130(Suppl 1):414.

    Google Scholar 

  76. Myklebust JH, Irish JM, Brody J, Czerwinski DK, Houot R, Kohrt HE, et al. High PD-1 expression and suppressed cytokine signaling distinguish T cells infiltrating follicular lymphoma tumors from peripheral T cells. Blood. 2013;121(8):1367–76.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Xu-Monette ZY, Zhou J, Young KH. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018;131(1):68–83.

    PubMed  CAS  Google Scholar 

  78. Jelinek T, Mihalyova J, Kascak M, Duras J, Hajek R. PD-1/PD-L1 inhibitors in haematological malignancies: update 2017. Immunology. 2017;152(3):357–71.

    Article  PubMed  CAS  Google Scholar 

  79. Goodman A, Patel SP, Kurzrock R. PD-1-PD-L1 immune-checkpoint blockade in B-cell lymphomas. Nat Rev Clin Oncol. 2016;advance online publication.

  80. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 2006;27(4):195–201.

    Article  PubMed  CAS  Google Scholar 

  81. Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol. 2016;34(23):2690–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Zinzani PL, Broccoli A. Possible novel agents in marginal zone lymphoma. Best Pract Res Clin Haematol. 2017;30(1–2):149–57.

    Article  PubMed  Google Scholar 

  83. •• Schuster SJ, Svoboda J, Chong EA, Nasta SD, Mato AR, Anak O, et al. Chimeric antigen receptor T cells in refractory B-cell lymphomas. N Engl J Med. 2017;377(26):2545–54. This study demonstrated impressive complete response rates and duration of remission heaviy pretreated patients with FL treated witih CAR-T therapy.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Chimeric antigen receptor T-cell therapy—assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15(1):47–62.

    Article  PubMed  CAS  Google Scholar 

  85. Park JH, Romero FA, Taur Y, Sadelain M, Brentjens RJ, Hohl TM, et al. Cytokine release syndrome grade is a predictive marker for infections in relapsed or refractory B-cell all patients treated with CAR T cells. Clinical Infectious Diseases: an official publication of the Infectious Diseases Society of America. 2018.

  86. Wang Z, Han W. Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy. Biomark Res. 2018;6:4.

    Article  PubMed  PubMed Central  Google Scholar 

  87. • Michot J-M, Bouabdallah R, Doorduijn JK, Vitolo U, Kersten MJ, Chiappella A, et al. CC-122, a novel cereblon modulating agent, in combination with obinutuzumab (GA101) in patients with relapsed and refractory (R/R) B-cell non-Hodgkin lymphoma (NHL). Blood. 2017;130(Suppl 1):411. Novel agent that may be beneficial in heavily pretreated patients with R/R FL.

    Google Scholar 

  88. Suneja G, Boyer M, Yehia BR, Shiels MS, Engels EA, Bekelman JE, et al. Cancer treatment in patients with HIV infection and non–AIDS-defining cancers: a survey of US oncologists. J Oncol Pract.. 2015;11(3):e380-e7.

    Article  Google Scholar 

  89. Suneja G, Lin CC, Simard EP, Han X, Engels EA, Jemal A. Disparities in cancer treatment among patients infected with the human immunodeficiency virus. Cancer. 2016;122(15):2399–407.

    Article  PubMed  CAS  Google Scholar 

  90. Becnel M, Flowers C, Nastoupil L. Disparities in lymphoma on the basis of race, gender, HIV status, and sexual orientation 2017. 8- p.

  91. Goodman A, Patel SP, Kurzrock R. PD-1-PD-L1 immune-checkpoint blockade in B-cell lymphomas. Nat Rev Clin Oncol. 2017;14(4):203–20.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 429, Houston, TX, 77030, USA

    Melody R. Becnel MD & Loretta J. Nastoupil MD

Authors
  1. Melody R. Becnel MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loretta J. Nastoupil MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melody R. Becnel MD.

Ethics declarations

Conflict of Interest

Melody R. Becnel declares that she has no conflict of interest.

Loretta J. Nastoupil has received research support from Celgene, Genentech, and TG Therapeutics, and she has also received compensation from Celgene, Genentech, Gilead Sciences, Novartis, and TG Therapeutics for service as a consultant.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Lymphoma

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Becnel, M.R., Nastoupil, L.J. Follicular Lymphoma: Past, Present, and Future. Curr. Treat. Options in Oncol. 19, 32 (2018). https://doi.org/10.1007/s11864-018-0550-0

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11864-018-0550-0

Keywords

Search

Navigation