open access

Vol 52, No 4 (2021)
Review article
Submitted: 2021-07-28
Accepted: 2021-07-28
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Role of targeted therapy in central nervous system lymphoma

Róża Kot1, Monika Długosz-Danecka1
DOI: 10.5603/AHP.2021.0066
·
Acta Haematol Pol 2021;52(4):345-348.
Affiliations
  1. Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, Poland

open access

Vol 52, No 4 (2021)
REVIEW ARTICLE
Submitted: 2021-07-28
Accepted: 2021-07-28

Abstract

Longer life expectancy, better diagnostic measures and advances in neuro-imaging account for the increasing numbers of diagnosed cases of primary central nervous system (CNS) lymphoma (PCNSL). Unfortunately, PCNSL is usually diagnosed late and that leads to poor performance status of patients, reducing their chances of accurate and timely therapy. This accounts for significant differences between real-life treatment outcomes and clinical trials. Although PCNSL had long been considered incurable, rapidly evolving therapeutic paradigms have shown significant progress with an absolute necessity for efficient diagnosis, staging and initiation of therapy conducted at experienced centers. High-dose methotrexate combined with rituximab and high-dose cytarabine in younger patients, or alkylating agents and rituximab in older patients, still remains the standard of care as induction therapy, while relapsed/refractory disease is a challenge necessitating the search for new, safe and effective therapeutic approaches.

Thanks to the discovery of the crucial molecular pathways leading to lymphomagenesis, it is now possible to target points of deregulation of specific pathways and stop the cancerous process. The very recent developments of efficient therapies, including high-dose methotrexate-based chemotherapy and targeted therapies comprising the monoclonal antibody rituximab and the immune checkpoint inhibitors lenalidomide and ibrutinib, have brought about improved outcomes.

Such novel agents bring hope for better results and seem to hold great promise for the treatment of patients with relapsed/refractory PCNSL. The key to future approaches is to target different molecular pathways in order to overcome mechanisms of resistance.

Abstract

Longer life expectancy, better diagnostic measures and advances in neuro-imaging account for the increasing numbers of diagnosed cases of primary central nervous system (CNS) lymphoma (PCNSL). Unfortunately, PCNSL is usually diagnosed late and that leads to poor performance status of patients, reducing their chances of accurate and timely therapy. This accounts for significant differences between real-life treatment outcomes and clinical trials. Although PCNSL had long been considered incurable, rapidly evolving therapeutic paradigms have shown significant progress with an absolute necessity for efficient diagnosis, staging and initiation of therapy conducted at experienced centers. High-dose methotrexate combined with rituximab and high-dose cytarabine in younger patients, or alkylating agents and rituximab in older patients, still remains the standard of care as induction therapy, while relapsed/refractory disease is a challenge necessitating the search for new, safe and effective therapeutic approaches.

Thanks to the discovery of the crucial molecular pathways leading to lymphomagenesis, it is now possible to target points of deregulation of specific pathways and stop the cancerous process. The very recent developments of efficient therapies, including high-dose methotrexate-based chemotherapy and targeted therapies comprising the monoclonal antibody rituximab and the immune checkpoint inhibitors lenalidomide and ibrutinib, have brought about improved outcomes.

Such novel agents bring hope for better results and seem to hold great promise for the treatment of patients with relapsed/refractory PCNSL. The key to future approaches is to target different molecular pathways in order to overcome mechanisms of resistance.

Get Citation

Keywords

diffuse large B-cell lymphoma, primary central nervous system lymphoma, targeted therapy

About this article
Title

Role of targeted therapy in central nervous system lymphoma

Journal

Acta Haematologica Polonica

Issue

Vol 52, No 4 (2021)

Article type

Review article

Pages

345-348

DOI

10.5603/AHP.2021.0066

Bibliographic record

Acta Haematol Pol 2021;52(4):345-348.

Keywords

diffuse large B-cell lymphoma
primary central nervous system lymphoma
targeted therapy

Authors

Róża Kot
Monika Długosz-Danecka

References (25)
  1. Green K, Hogg JP. Central nervous system lymphoma. StatPearls. StatPearls, Treasure Island 2021.
  2. Deckert M, Engert A, Brück W, et al. Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma. Leukemia. 2011; 25(12): 1797–1807.
  3. Shiels MS, Pfeiffer RM, Besson C, et al. Trends in primary central nervous system lymphoma incidence and survival in the U.S. Br J Haematol. 2016; 174(3): 417–424.
  4. Grommes C, Rubenstein JL, DeAngelis LM, et al. Comprehensive approach to diagnosis and treatment of newly diagnosed primary CNS lymphoma. Neuro Oncol. 2019; 21(3): 296–305.
  5. Zeremski V, Koehler M, Fischer T, et al. Characteristics and outcome of patients with primary CNS lymphoma in a "real-life" setting compared to a clinical trial. Ann Hematol. 2016; 95(5): 793–799.
  6. Ferreri AJ. Therapy of primary CNS lymphoma: role of intensity, radiation, and novel agents. Hematology Am Soc Hematol Educ Program. 2017; 2017(1): 565–577.
  7. Ferreri AJM, Holdhoff M, Nayak L, et al. Evolving treatments for primary central nervous system lymphoma. Am Soc Clin Oncol Educ Book. 2019; 39: 454–466.
  8. Courts C, Montesinos-Rongen M, Martin-Subero JI, et al. Transcriptional profiling of the nuclear factor-kappaB pathway identifies a subgroup of primary lymphoma of the central nervous system with low BCL10 expression. J Neuropathol Exp Neurol. 2007; 66(3): 230–237.
  9. Montesinos-Rongen M, Schmitz R, Brunn A, et al. Mutations of CARD11 but not TNFAIP3 may activate the NF-kappaB pathway in primary CNS lymphoma. Acta Neuropathol. 2010; 120(4): 529–535.
  10. Deckert-Schlüter M, Rang A, Wiestler OD. Apoptosis and apoptosis-related gene products in primary non-Hodgkin's lymphoma of the central nervous system. Acta Neuropathol. 1998; 96(2): 157–162.
  11. Ferreri AJM, Reni M, Foppoli M, et al. International Extranodal Lymphoma Study Group (IELSG). High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet. 2009; 374(9700): 1512–1520.
  12. 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.
  13. Kasenda B, Ferreri AJM, Marturano E, et al. First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)--a systematic review and individual patient data meta-analysis. Ann Oncol. 2015; 26(7): 1305–1313.
  14. Citterio G, Reni M, Ferreri AJ. Present and future treatment options for primary CNS lymphoma. Expert Opin Pharmacother. 2015; 16(17): 2569–2579.
  15. 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.
  16. 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.
  17. Ferreri AJM, Cwynarski K, Pulczynski E, et al. International Extranodal Lymphoma Study Group (IELSG), 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.
  18. 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.
  19. 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.
  20. 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.
  21. Musuraca G, Fattori PP, Ceccolini M, et al. Prolonged 18FDG-PET negative complete remission in a heavily pretreated, elderly patient with diffuse large B cell lymphoma treated with lenalidomide, low dose dexamethasone, and colony stimulating factor (Rd-G). Am J Hematol. 2011; 86(1): 79–80.
  22. 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.
  23. Cox MC, Mannino G, Lionetto L, et al. Lenalidomide for aggressive B-cell lymphoma involving the central nervous system? Am J Hematol. 2011; 86(11): 957.
  24. 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.
  25. 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.

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