Skip to main content

Advertisement

SpringerLink
Log in

Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis

  • Research
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Bruton’s tyrosine kinase inhibitors (BTKi) exhibit superior efficacy in relapsed/refractory primary central nervous system lymphoma (PCNSL), but few studies have evaluated patients with newly diagnosed PCNSL, and even fewer studies have evaluated differences in efficacy between treatment with BTKi and traditional chemotherapy. This study retrospectively analyzed the clinical characteristics of 86 patients with PCNSL and identified predictors of poor prognosis for overall survival (OS). After excluding patients who only received palliative care, 82 patients were evaluated for efficacy and survival. According to the induction regimen, patients were divided into the traditional chemotherapy, BTKi combination therapy, and radiotherapy groups; the objective response rates (ORR) of the three groups were 71.4%, 96.2%, and 71.4% (P = 0.037), respectively. Both median progression-free survival and median duration of remission showed statistically significant differences (P = 0.019 and P = 0.030, respectively). The median OS of the BTKi-containing therapy group was also longer than that of the traditional chemotherapy group (not reached versus 47.8 (32.5–63.1) months, P = 0.038).Seventy-one patients who achieved an ORR were further analyzed, and achieved an ORR after four cycles of treatment and maintenance therapy had prolonged OS (P = 0.003 and P = 0.043, respectively). In conclusion, survival, and prognosis of patients with newly diagnosed PCNSL are influenced by the treatment regimen, with the BTKi-containing regimen showing great potential.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  1. Villano JL, Koshy M, Shaikh H et al (2011) Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer 105(9):1414–1418. https://doi.org/10.1038/bjc.2011.357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Mendez JS, Ostrom QT, Gittleman H et al (2018) The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades. Neurooncology 20(5):687–694. https://doi.org/10.1093/neuonc/nox187

    Article  Google Scholar 

  3. Barajas RF, Politi LS, Anzalone N et al (2021) Consensus recommendations for MRI and PET imaging of primary central nervous system lymphoma: guideline statement from the International Primary CNS Lymphoma Collaborative Group (IPCG). Neurooncology 23(7):1056–1071. https://doi.org/10.1093/neuonc/noab020

    Article  CAS  Google Scholar 

  4. Chen T, Liu Y, Wang Y et al (2022) Evidence-based expert consensus on the management of primary central nervous system lymphoma in China. J Hematol Oncol 15(1):136. https://doi.org/10.1186/s13045-022-01356-7

    Article  PubMed  PubMed Central  Google Scholar 

  5. Loghavi S, Kanagal-Shamanna R, Khoury JD et al (2023) Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc, 100397. https://doi.org/10.1016/j.modpat.2023.100397. 5th edition of the world health classification of tumors of the hematopoietic and lymphoid tissues. Advance online publication

  6. Lebrun L, Allard-Demoustiez S, Salmon I (2023) Pathology and new insights in central nervous system lymphomas. Curr Opin Oncol 35(5):347–356. https://doi.org/10.1097/CCO.0000000000000978

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Woo HY, Chae SW, DO SI et al (2022) Clinicopathological characterization of primary diffuse large B-Cell lymphoma of the Central Nervous System. Anticancer Res 42(11):5601–5608. https://doi.org/10.21873/anticanres.16068

    Article  CAS  PubMed  Google Scholar 

  8. Ferreri AJM, Calimeri T, Cwynarski K et al (2023) Primary central nervous system lymphoma. Nat Reviews Disease Primers 9(1):29. https://doi.org/10.1038/s41572-023-00439-0

    Article  PubMed  Google Scholar 

  9. Schaff LR, Grommes C (2022) Primary central nervous system lymphoma. Blood 140(9):971–979. https://doi.org/10.1182/blood.2020008377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yuan Y, Ding T, Wang S et al (2021) Current and emerging therapies for primary central nervous system lymphoma. Biomark Res 9(1):32. https://doi.org/10.1186/s40364-021-00282-z

    Article  PubMed  PubMed Central  Google Scholar 

  11. Shibamoto Y, Ogino H, Hasegawa M et al (2005) Results of radiation monotherapy for primary central nervous system lymphoma in the 1990s. Int J Radiat Oncol Biol Phys 62(3):809–813. https://doi.org/10.1016/j.ijrobp.2004.12.043

    Article  PubMed  Google Scholar 

  12. Houillier C, Soussain C, Ghesquières H et al (2020) Management and outcome of primary CNS lymphoma in the modern era: an LOC network study. Neurology 94(10):e1027–e1039. https://doi.org/10.1212/WNL.0000000000008900

    Article  PubMed  PubMed Central  Google Scholar 

  13. Lewis KL, Cheah CY (2021) Non-covalent BTK inhibitors-the New BTKids on the Block for B-Cell malignancies. J Personalized Med 11(8):764. https://doi.org/10.3390/jpm11080764

    Article  Google Scholar 

  14. Leitinger DE, Kaplan DZ (2022) BTK inhibitors in Haematology: Beyond B Cell malignancies. Transfus Med Rev 36(4):239–245. https://doi.org/10.1016/j.tmrv.2022.06.009

    Article  PubMed  Google Scholar 

  15. Bonzheim I, Sander P, Salmerón-Villalobos J et al (2022) The molecular hallmarks of primary and secondary vitreoretinal lymphoma. Blood Adv 6(5):1598–1607. https://doi.org/10.1182/bloodadvances.2021004212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pal Singh S, Dammeijer F, Hendriks RW (2018) Role of Bruton’s tyrosine kinase in B cells and malignancies. Mol Cancer 17(1):57. https://doi.org/10.1186/s12943-018-0779-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cetin GO, Baris IC, Caner V et al (2016) Mutational status of EZH2 and CD79B hot spots in mature B-cell non-hodgkin’s lymphomas: novel CD79B variations have been revealed. Eur Rev Med Pharmacol Sci 20(5):830–836

    CAS  PubMed  Google Scholar 

  18. Wu K, Zhang H, Fu Y et al (2018) TLR4/MyD88 signaling determines the metastatic potential of breast cancer cells. Mol Med Rep 18(3):3411–3420. https://doi.org/10.3892/mmr.2018.9326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ollila TA, Olszewski AJ (2018) Extranodal diffuse large B cell lymphoma: molecular features, prognosis, and risk of Central Nervous System recurrence. Curr Treat Options Oncol 19(8):38. https://doi.org/10.1007/s11864-018-0555-8

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nagane M (2022) Molecular pathogenesis and therapeutic development of primary central nervous system lymphoma: update and future perspectives. Japanese J Clin Hematol 63(9):1145–1156. https://doi.org/10.11406/rinketsu.63.1145

    Article  Google Scholar 

  21. Grommes C, Tang SS, Wolfe J et al (2019) Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma. Blood 133(5):436–445. https://doi.org/10.1182/blood-2018-09-875732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Soussain C, Choquet S, Blonski M et al (2019) 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. European journal of cancer (Oxford, England: 1990), 117, 121–130. https://doi.org/10.1016/j.ejca.2019.05.024

  23. Abrey LE, Batchelor TT, Ferreri AJ, International Primary CNS Lymphoma Collaborative Group (2005) Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncology: Official J Am Soc Clin Oncol 23(22):5034–5043. https://doi.org/10.1200/JCO.2005.13.524

    Article  Google Scholar 

  24. Batchelor TT (2016) Primary central nervous system lymphoma. Hematology. American Society of Hematology. Education Program, 2016(1), 379–385. https://doi.org/10.1182/asheducation-2016.1.379

  25. Tang D, Chen Y, Shi Y et al (2022) Epidemiologic Characteristics, prognostic factors, and treatment outcomes in primary Central Nervous System Lymphoma: a SEER-Based study. Front Oncol 12:817043. https://doi.org/10.3389/fonc.2022.817043

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chen C, Sun P, Sun XQ et al (2023) Primary treatment and recent survival trends in patients with primary diffuse large B-cell lymphoma of central nervous system, 1995–2016: a population-based SEER analysis. Hematol Oncol 41(2):248–256. https://doi.org/10.1002/hon.2918

    Article  PubMed  Google Scholar 

  27. van der Meulen M, Dinmohamed AG, Visser O et al (2017) Improved survival in primary central nervous system lymphoma up to age 70 only: a population-based study on incidence, primary treatment and survival in the Netherlands, 1989–2015. Leukemia 31(8):1822–1825. https://doi.org/10.1038/leu.2017.128

    Article  PubMed  Google Scholar 

  28. Farrall AL, Smith JR (2021) Changing incidence and survival of primary Central Nervous System Lymphoma in Australia: a 33-Year National Population-based study. Cancers 13(3):403. https://doi.org/10.3390/cancers13030403

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fukumura K, Kawazu M, Kojima S et al (2016) Genomic characterization of primary central nervous system lymphoma. Acta Neuropathol 131(6):865–875. https://doi.org/10.1007/s00401-016-1536-2

    Article  CAS  PubMed  Google Scholar 

  30. Nayyar N, White MD, Gill CM et al (2019) MYD88 L265P mutation and CDKN2A loss are early mutational events in primary central nervous system diffuse large B-cell lymphomas. Blood Adv 3(3):375–383. https://doi.org/10.1182/bloodadvances.2018027672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lee JH, Jeong H, Choi JW et al (2017) Clinicopathologic significance of MYD88 L265P mutation in diffuse large B-cell lymphoma: a meta-analysis. Sci Rep 7(1):1785. https://doi.org/10.1038/s41598-017-01998-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ferreri AJ, Blay JY, Reni M et al (2003) Prognostic scoring system for primary CNS lymphomas: the International Extranodal Lymphoma Study Group experience. J Clin Oncology: Official J Am Soc Clin Oncol 21(2):266–272. https://doi.org/10.1200/JCO.2003.09.139

    Article  Google Scholar 

  33. Abrey LE, Ben-Porat L, Panageas KS et al (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncology: Official J Am Soc Clin Oncol 24(36):5711–5715. https://doi.org/10.1200/JCO.2006.08.2941

    Article  Google Scholar 

  34. Liu CJ, Lin SY, Yang CF et al (2020) A new prognostic score for disease progression and mortality in patients with newly diagnosed primary CNS lymphoma. Cancer Med 9(6):2134–2145. https://doi.org/10.1002/cam4.2872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Shen J, Liu J (2022) Bruton’s tyrosine kinase inhibitors in the treatment of primary central nervous system lymphoma: a mini-review. Front Oncol 12:1034668. https://doi.org/10.3389/fonc.2022.1034668

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Grommes C, Pastore A, Palaskas N et al (2017) Ibrutinib unmasks critical role of Bruton Tyrosine Kinase in Primary CNS Lymphoma. Cancer Discov 7(9):1018–1029. https://doi.org/10.1158/2159-8290.CD-17-0613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Renaud L, Bossard JB, Carpentier B et al (2021) Treatment with temozolomide and ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL). Eur J Haematol 107(3):370–373. https://doi.org/10.1111/ejh.13667

    Article  CAS  PubMed  Google Scholar 

  38. Lauer EM, Waterhouse M, Braig M et al (2020) Ibrutinib in patients with relapsed/refractory central nervous system lymphoma: a retrospective single-centre analysis. Br J Haematol 190(2):e110–e114. https://doi.org/10.1111/bjh.16759

    Article  CAS  PubMed  Google Scholar 

  39. Lewis KL, Chin CK, Manos K et al (2021) Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience. Br J Haematol 192(6):1049–1053. https://doi.org/10.1111/bjh.16946

    Article  CAS  PubMed  Google Scholar 

  40. Estupiñán HY, Berglöf A, Zain R et al (2021) Comparative analysis of BTK inhibitors and mechanisms underlying adverse effects. Front cell Dev Biology 9:630942. https://doi.org/10.3389/fcell.2021.630942

    Article  Google Scholar 

  41. Munir T, Brown JR, O’Brien S et al (2019) Final analysis from RESONATE: up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol 94(12):1353–1363. https://doi.org/10.1002/ajh.25638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lionakis MS, Dunleavy K, Roschewski M et al (2017) Inhibition of B cell receptor signaling by Ibrutinib in primary CNS Lymphoma. Cancer Cell 31(6):833–843e5. https://doi.org/10.1016/j.ccell.2017.04.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Zhang Y, Li Y, Zhuang Z et al (2021) Preliminary evaluation of Zanubrutinib-Containing regimens in DLBCL and the cerebrospinal fluid distribution of Zanubrutinib: a 13-Case Series. Front Oncol 11:760405. https://doi.org/10.3389/fonc.2021.760405

    Article  PubMed  PubMed Central  Google Scholar 

  44. Song Y, Deng L, Zhang B et al (2021) Preliminary results of orelabrutinib concentrations in peripheral blood and cerebrospinal fluid in patients with relapsed/refractory primary or secondary CNS lymphoma. In CSCO, 24th Annual Meeting

  45. Hillmen P, Brown JR, Eichhorst BF et al (2020) ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Future Oncol (London England) 16(10):517–523. https://doi.org/10.2217/fon-2019-0844

    Article  CAS  Google Scholar 

  46. Tam CS, Opat S, D’Sa S et al (2020) A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood 136(18):2038–2050. https://doi.org/10.1182/blood.2020006844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Dhillon S (2021) Orelabrutinib: first approval. Drugs 81(4):503–507. https://doi.org/10.1007/s40265-021-01482-5

    Article  CAS  PubMed  Google Scholar 

  48. Zhao S, Liu Y, Zhu Z et al (2022) Orelabrutinib, Rituximab, and high-dose methotrexate (HD-MTX) in newly diagnosed primary Central Nervous System Lymphoma (PCNSL): a retrospective analysis on Efficacy, Safety, and Biomarker. Blood 140(Supplement 1):1338–1339

    Article  Google Scholar 

  49. Vu K, Mannis G, Hwang J et al (2019) Low-dose lenalidomide maintenance after induction therapy in older patients with primary central nervous system lymphoma. Br J Haematol 186(1):180–183. https://doi.org/10.1111/bjh.15787

    Article  PubMed  PubMed Central  Google Scholar 

  50. Faivre G, Butler MJ, Le I et al (2019) Temozolomide as a single Agent maintenance therapy in Elderly patients with primary CNS lymphoma. Clin Lymphoma Myeloma Leuk 19(10):665–669. https://doi.org/10.1016/j.clml.2019.05.012

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank all participating institutions and physicians for their support of this study.

Funding

This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Hematology, Second Hospital of Shanxi Medical University, No.382 Wuyi Road, Xinghualing District, Taiyuan, Shanxi, 030000, China

    Si-Jun Bai & Lin-Hua Yang

  2. Department of Hematology, Shanxi Provincial People’s Hospital, Taiyuan, 030000, China

    Si-Jun Bai, Jian-Xia He, Ye Geng, Yi-Nan Gao, Cai-Xia Zhang, Ya-Ru Wang, Li-Yuan Qin & Wen-Jun Wang

  3. Department of Hematology, First Hospital of Shanxi Medical University, Taiyuan, 030000, China

    Yuan-Jun Zheng

Authors
  1. Si-Jun Bai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian-Xia He
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuan-Jun Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ye Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi-Nan Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cai-Xia Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ya-Ru Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Li-Yuan Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wen-Jun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lin-Hua Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Bai SJ and Yang LH were the main authors of the paper, and equally designed and planned the study; Bai SJ wrote the manuscript; Bai SJ, Yang LH and He JX oversaw data pooling, data checking and statistical analysis; Zheng YJ, Geng Y, Gao YN, Zhang CX and Wang YR made contributions to the acquisition of clinical data.Qin LY and Wang WJ performed the collection and collation of the experimental data.All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Lin-Hua Yang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bai, SJ., He, JX., Zheng, YJ. et al. Clinical characteristics and prognosis of patients with newly diagnosed primary central nervous system lymphoma: a multicentre retrospective analysis. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05797-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00277-024-05797-7

Keywords

Search

Navigation