629
Views
0
CrossRef citations to date
0
Altmetric
Reviews

Primary CNS lymphoma: update on molecular pathogenesis and therapy

, &
Pages 57-65 | Received 20 Jul 2022, Accepted 30 Sep 2022, Published online: 26 Oct 2022

References

  • Lv C, Wang J, Zhou M, et al. Primary Central nervous system lymphoma in the United States, 1975–2017. Ther Adv Hematol. 2022;13:20406207211066166.
  • Olson JE, Janney CA, Rao RD, et al. The continuing increase in the incidence of primary Central nervous system non-Hodgkin lymphoma. Cancer. 2002;95(7):1504–1510.
  • Schabet M. Epidemiology of primary CNS lymphoma. J Neurooncol. 1999;43(3):199–201.
  • Mahale P, Shiels MS, Lynch CF, et al. Incidence and outcomes of primary central nervous system lymphoma in solid organ transplant recipients. Am J Transplant. 2018;18(2):453–461.
  • Lai R, Rosenblum MK, DeAngelis LM. Primary CNS lymphoma: a whole-brain disease? Neurology. 2002;59(10):1557–1562.
  • Rubenstein JL, Fridlyand J, Shen A, et al. Gene expression and angiotropism in primary CNS lymphoma. Blood. 2006;107(9):3716–3723.
  • Braaten KM, Betensky RA, de Leval L, et al. BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma. Clin Cancer Res. 2003;9(3):1063–1069.
  • Montesinos-Rongen M, Brunn A, Bentink S, et al. Gene expression profiling suggests primary central nervous system lymphomas to be derived from a late germinal center B cell. Leukemia. 2008;22(2):400–405.
  • Mondello P, Cuzzocrea S, Arrigo C, et al. STAT6 activation correlates with cerebrospinal fluid IL-4 and IL-10 and poor prognosis in primary central nervous system lymphoma. Hematol Oncol. 2020;38(1):106–110.
  • Sasayama T, Nakamizo S, Nishihara M, et al. Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro Oncol. 2012;14(3):368–380.
  • Rubenstein JL, Wong VS, Kadoch C, et al. CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood. 2013;121(23):4740–4748.
  • Villa D, Tan KL, Steidl C, et al. Molecular features of a large cohort of primary central nervous system lymphoma using tissue microarray. Blood Adv. 2019;3(23):3953–3961.
  • Kim S, Nam SJ, Kwon D, et al. MYC and BCL2 overexpression is associated with a higher class of Memorial Sloan-Kettering Cancer Center prognostic model and poor clinical outcome in primary diffuse large B-cell lymphoma of the central nervous system. BMC Cancer. 2016;16(1):363.
  • Nakamura T, Tateishi K, Niwa T, et al. Recurrent mutations of CD79B and MYD88 are the hallmark of primary central nervous system lymphomas. Neuropathol Appl Neurobiol. 2016;42(3):279–290.
  • Fukumura K, Kawazu M, Kojima S, et al. Genomic characterization of primary central nervous system lymphoma. Acta Neuropathol. 2016;131(6):865–875.
  • Braggio E, Van Wier S, Ojha J, et al. Genome-Wide analysis uncovers novel recurrent alterations in primary Central nervous system lymphomas. Clin Cancer Res. 2015;21(17):3986–3994.
  • Vater I, Montesinos-Rongen M, Schlesner M, et al. The mutational pattern of primary lymphoma of the central nervous system determined by whole-exome sequencing. Leukemia. 2015;29(3):677–685.
  • Gonzalez-Aguilar A, Idbaih A, Boisselier B, et al. Recurrent mutations of MYD88 and TBL1XR1 in primary central nervous system lymphomas. Clin Cancer Res. 2012;18(19):5203–5211.
  • Chapuy B, Roemer MGM, Stewart C, et al. Targetable genetic features of primary testicular and primary central nervous system lymphomas. Blood. 2016;127(7):869–881.
  • Gandhi MK, Hoang T, Law SC, et al. EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity. Blood. 2021;137(11):1468–1477.
  • Nayyar N, White MD, Gill CM, et al. MYD88 L265P mutation and CDKN2A loss are early mutational events in primary central nervous system diffuse large B-cell lymphomas. Blood Adv. 2019;3(3):375–383.
  • Radke J, Ishaque N, Koll R, et al.; ICGC MMML-Seq Consortium. The genomic and transcriptional landscape of primary central nervous system lymphoma. Nat Commun. 2022;13(1):2558.
  • Schmitz R, Wright GW, Huang DW, et al. Genetics and pathogenesis of diffuse large B-Cell lymphoma. N Engl J Med. 2018;378(15):1396–1407.
  • Güney E, Lucas C-HG, Qi Z, et al. A genetically distinct pediatric subtype of primary CNS large B-cell lymphoma is associated with favorable clinical outcome. Blood Adv. 2022;6(10):3189–3193.
  • Geng H, Tsang M, Subbaraj L, et al. Tumor metabolism and neurocognition in CNS lymphoma. Neuro Oncol. 2021;23(10):1668–1679.
  • Barajas RF, Politi LS, Anzalone N, et al. Consensus recommendations for MRI and PET imaging of primary Central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG). Neuro Oncol. 2021;23(7):1056–1071.
  • Margold M, Seidel S, Kowalski T, et al. The value of bone marrow biopsy for staging of patients with primary CNS lymphoma. Neuro Oncol. 2021;23(12):2076–2084.
  • Bobillo S, Crespo M, Escudero L, et al. Cell free circulating tumor DNA in cerebrospinal fluid detects and monitors central nervous system involvement of B-cell lymphomas. Haematologica. 2021;106(2):513–521.
  • Mutter JA. Profiling of circulating tumor DNA for noninvasive disease detection, risk stratification, and MRD monitoring in patients with CNS lymphoma. Proc. American Society of Hematology Annual Meeting 2021 Blood (2021) 138 (Supplement 1): 6.
  • Kurtz DM, Soo J, Co Ting Keh L, et al. Enhanced detection of minimal residual disease by targeted sequencing of phased variants in circulating tumor DNA. Nat Biotechnol. 2021;39(12):1537–1547.
  • Tan WJ, Wang MM, Ricciardi-Castagnoli P, et al. Single-cell MYD88 sequencing of isolated B cells from vitreous biopsies aids vitreoretinal lymphoma diagnosis. Blood. 2019;134(8):709–712.
  • Ervin T, Canellos GP. Successful treatment of recurrent primary central nervous system lymphoma with high-dose methotrexate. Cancer. 1980;45(7):1556–1557.
  • Skarin AT, Zuckerman KS, Pitman SW, et al. High-dose methotrexate with folinic acid in the treatment of advanced non-Hodgkin lymphoma including CNS involvement. Blood. 1977;50(6):1039–1047.
  • Thomas S, Fisher KH, Snowden JA, et al. Methotrexate is a JAK/STAT pathway inhibitor. PLoS One. 2015;10(7):e0130078.
  • Majumdar S, Aggarwal BB. Methotrexate suppresses NF-kappaB activation through inhibition of IkappaBalpha phosphorylation and degradation. J Immunol. 2001;167(5):2911–2920.
  • DeAngelis LM, Seiferheld W, Schold SC, et al. Combination chemotherapy and radiotherapy for primary Central nervous system lymphoma: Radiation Therapy Oncology Group Study 93-10. J Clin Oncol. 2002;20(24):4643–4648.
  • Nelson DF, Martz KL, Bonner H, et al. Non-Hodgkin’s lymphoma of the brain: can high dose, large volume radiation therapy improve survival? Report on a prospective trial by the Radiation Therapy Oncology Group (RTOG): RTOG 8315. Int J Radiat Oncol Biol Phys. 1992;23(1):9–17.
  • Abrey LE, DeAngelis LM, Yahalom J. Long-term survival in primary CNS lymphoma. J Clin Oncol. 1998;16(3):859–863.
  • Ferreri AJM, Cwynarski K, Pulczynski E, et al.; International Extranodal Lymphoma Study Group (IELSG). Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol. 2016;3(5):e217–e227.
  • Bromberg JEC, Issa S, Bakunina K, et al. Rituximab in patients with primary CNS lymphoma (HOVON 105/ALLG NHL 24): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2019;20(2):216–228.
  • Schmitt AM, Herbrand AK, Fox CP, et al. Rituximab in primary central nervous system lymphoma—a systematic review and meta-analysis. Hematol Oncol. 2019;37(5):548–557.
  • DeAngelis LM, Yahalom J, Thaler HT, et al. Combined modality therapy for primary CNS lymphoma. J Clin Oncol. 1992;10(4):635–643.
  • Morris PG, Correa DD, Yahalom J, et al. Rituximab, methotrexate, procarbazine, and vincristine followed by consolidation reduced-dose whole-brain radiotherapy and cytarabine in newly diagnosed primary CNS lymphoma: final results and long-term outcome. J Clin Oncol. 2013;31(31):3971–3979.
  • Omuro AMP, DeAngelis LM, Karrison T, NRG, et al. Randomized phase II study of rituximab, methotrexate (MTX), procarbazine, vincristine, and cytarabine (R-MPV-A) with and without low-dose whole-brain radiotherapy (LD-WBRT) for newly diagnosed primary CNS lymphoma (PCNSL). J Clin Oncol. 2020;38(15_suppl):2501–2501.
  • Wieduwilt MJ, Valles F, Issa S, et al. Immunochemotherapy with intensive consolidation for primary CNS lymphoma: a pilot study and prognostic assessment by diffusion-weighted MRI. Clin Cancer Res. 2012;18(4):1146–1155.
  • Rubenstein JL, Hsi ED, Johnson JL, et al. Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol. 2013;31(25):3061–3068.
  • Birsen R, Willems L, Pallud J, et al. Efficacy and safety of high-dose etoposide cytarabine as consolidation following rituximab methotrexate temozolomide induction in newly diagnosed primary Central nervous system lymphoma in immunocompetent patients. Haematologica. 2018;103(7):e296–e299.
  • Omuro A, Correa DD, DeAngelis LM, et al. R-MPV followed by high-dose chemotherapy with TBC and autologous stem-cell transplant for newly diagnosed primary CNS lymphoma. Blood. 2015;125(9):1403–1410.
  • Illerhaus G, Kasenda B, Ihorst G, et al. High-dose chemotherapy with autologous haemopoietic stem cell transplantation for newly diagnosed primary CNS lymphoma: a prospective, single-arm, phase 2 trial. Lancet Haematol. 2016;3(8):e388-397–e397.
  • Houillier C, Taillandier L, Dureau S, et al.; Intergroupe GOELAMS–ANOCEF and the LOC Network for CNS Lymphoma. Radiotherapy or autologous Stem-Cell transplantation for primary CNS lymphoma in patients 60 years of age and younger: results of the Intergroup ANOCEF-GOELAMS Randomized Phase II PRECIS Study. J Clin Oncol. 2019;37(10):823–833.
  • Ferreri AJM, Cwynarski K, Pulczynski E, et al.; International Extranodal Lymphoma Study Group (IELSG). Whole-brain radiotherapy or autologous stem-cell transplantation as consolidation strategies after high-dose methotrexate-based chemoimmunotherapy in patients with primary CNS lymphoma: results of the second randomisation of the International Extranodal Lymphoma Study Group-32 phase 2 trial. Lancet Haematol. 2017;4(11):e510–e523.
  • Scordo M, Wang TP, Ahn KW, et al. Outcomes associated with thiotepa-based conditioning in patients with primary central nervous system lymphoma after autologous hematopoietic cell transplant. JAMA Oncol. 2021;7(7):993–1003.
  • Batchelor T, Giri S, Ruppert AS, et al. Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: results of CALGB 51101 (Alliance). J Clin Oncol. 2021;39(15_suppl):7506–7506.
  • Omuro A, Chinot O, Taillandier L, et al. Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. Lancet Haematol. 2015;2(6):e251-259–e259.
  • Rubenstein JL, Geng H, Fraser EJ, et al. Phase 1 investigation of lenalidomide/rituximab plus outcomes of lenalidomide maintenance in relapsed CNS lymphoma. Blood Adv. 2018;2(13):1595–1607.
  • Vu K, Mannis G, Hwang J, et al. Low-dose lenalidomide maintenance after induction therapy in older patients with primary central nervous system lymphoma. Br J Haematol. 2019;186(1):180–183.
  • Ghesquieres H, Chevrier M, Laadhari M, et al. Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective ‘proof of concept’ phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA). Ann Oncol. 2019;30(4):621–628.
  • Tun HW, Johnston PB, DeAngelis LM, et al. Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma. Blood. 2018;132(21):2240–2248.
  • Carpio C, Bouabdallah R, Ysebaert L, et al. Avadomide monotherapy in relapsed/refractory DLBCL: safety, efficacy, and a predictive gene classifier. Blood. 2020;135(13):996–1007.
  • National Cancer Institute (NCI). 2022. Phase I trial of methotrexate, rituximab, lenalidomide, and nivolumab (Nivo-MR2) induction followed by lenalidomide and nivolumab maintenance in primary CNS lymphoma. (NCT04609046).
  • Zinzani PL, Rodgers T, Marino D, et al. RE-MIND: comparing tafasitamab + lenalidomide (L-MIND) with a real-world lenalidomide monotherapy cohort in relapsed or refractory diffuse large B-cell lymphoma. Clin Cancer Res. 2021;27(22):6124–6134.
  • Grommes C, Pastore A, Palaskas N, et al. Ibrutinib unmasks critical role of Bruton tyrosine kinase in primary CNS lymphoma. Cancer Discov. 2017;7(9):1018–1029.
  • Soussain C, Choquet S, Blonski M, et al. Ibrutinib monotherapy for relapse or refractory primary CNS lymphoma and primary vitreoretinal lymphoma: final analysis of the phase II ‘proof-of-concept’ iLOC study by the lymphoma study association (LYSA) and the French oculo-cerebral lymphoma (LOC) network. Eur J Cancer. 2019;117:121–130.
  • Grommes C, Tang SS, Wolfe J, et al. Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma. Blood. 2019;133(5):436–445.
  • Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma. Cancer Cell. 2017;31(6):833–843.e5.
  • Narita Y, Nagane M, Mishima K, et al. Phase I/II study of tirabrutinib, a second-generation Bruton’s tyrosine kinase inhibitor, in relapsed/refractory primary Central nervous system lymphoma. Neuro Oncol. 2021;23(1):122–133.
  • Nayak L, Iwamoto FM, LaCasce A, et al. PD-1 blockade with nivolumab in relapsed/refractory primary Central nervous system and testicular lymphoma. Blood. 2017;129(23):3071–3073.
  • Ambady P, Szidonya L, Firkins J, et al. Combination immunotherapy as a non-chemotherapy alternative for refractory or recurrent CNS lymphoma. Leuk Lymphoma. 2019;60(2):515–518.
  • Hoang-Xuan K, Houot R, Soussain C, et al. First results of the acsé pembrolizumab phase II in the primary CNS lymphoma (PCNSL) cohort. Blood. 2020;136(Supplement 1):15–16.
  • Nayak L, Iwamoto FM, Ferreri AJ, et al. Checkmate 647: a phase 2, Open-Label study of nivolumab in relapsed/refractory primary Central nervous system lymphoma or relapsed/refractory primary testicular lymphoma. Hematol Oncol. 2017;35:420–421.
  • Siddiqi T, Wang X, Blanchard MS, et al. CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma. Blood Adv. 2021;5(20):4059–4063.
  • Frigault MJ, Dietrich J, Gallagher K, et al. Safety and efficacy of tisagenlecleucel in primary CNS lymphoma: a phase 1/2 clinical trial. Blood. 2022;139(15):2306–2315.
  • van der Meulen M, Dirven L, Bakunina K, et al. MMSE is an independent prognostic factor for survival in primary central nervous system lymphoma. J Neurooncol. 2021;152(2):357–362.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.