Vol 52, No 4 (2021)
Review article
Published online: 2021-08-31
Primary central nervous system lymphoma: how to treat younger patients
Acta Haematol Pol 2021;52(4):340-344.
Abstract
Primary central nervous system lymphoma (PCNSL) is a rare subtype of extranodal lymphoma which is associated with a relatively poor prognosis compared to other diffuse large B-cell lymphomas.
Population-based cancer registry data demonstrates that there has been a significant improvement in the survival of patients with PCNSL over the past two decades. This improvement likely reflects the introduction of high-intensity chemotherapy based on an induction regimen with high-dose methotrexate, and consolidation strategy including autologous stem cell transplantation. As a result, the improvement has been mainly observed in younger patients. New approaches such as Bruton tyrosine kinase inhibitor, immunomodulatory agents, immune checkpoint inhibition, and chimeric antigen receptor T-cell therapy are under investigation for PCNSL. In addition, trials combining novel agents in front-line induction treatment are ongoing.
Keywords: primary central nervous system lymphomaPCNSLHD-MTXmethotrexate
References
- Graham MS, DeAngelis LM. Improving outcomes in primary CNS lymphoma. Best Pract Res Clin Haematol. 2018; 31(3): 262–269.
- Holdhoff M, Mrugala MM, Grommes C, et al. Challenges in the treatment of newly diagnosed and recurrent primary central nervous system lymphoma. J Natl Compr Canc Netw. 2020; 18(11): 1571–1578.
- Abrey LE, Ben-Porat L, Panageas KS. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol. 2006; 24(36): 5711–5715.
- Kim P, Omuro A. Consolidation therapy in primary central nervous system lymphoma. Curr Treat Options Oncol. 2020; 21(9): 74.
- 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.
- 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.
- Van Dijck R, Doorduijn JK, Bromberg JEC. The role of rituximab in the treatment of primary central nervous system lymphoma. Cancers (Basel). 2021; 13(8).
- 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.
- 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.
- 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.
- Houillier C, Soussain C, Ghesquières H, et al. Intergroupe GOELAMS–ANOCEF and the LOC Network for CNS Lymphoma. Recurrent mutations of MYD88 and TBL1XR1 in primary central nervous system lymphomas. Clin Cancer Res. 2012; 18(19): 5203–5211.
- Fox CP, Phillips EH, Smith J, et al. British Society for Haematology. Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma. Br J Haematol. 2019; 184(3): 348–363.
- Thiel E, Korfel A, Martus P, et al. High-dose methotrexate with or without whole brain radiotherapy for primary CNS lymphoma (G-PCNSL-SG-1): a phase 3, randomised, non-inferiority trial. Lancet Oncol. 2010; 11(11): 1036–1047.
- Korfel A, Thiel E, Martus P, et al. Randomized phase III study of whole-brain radiotherapy for primary CNS lymphoma. Neurology. 2015; 84(12): 1242–1248.
- Herrlinger U, Schäfer N, Fimmers R, et al. Early whole brain radiotherapy in primary CNS lymphoma: negative impact on quality of life in the randomized G-PCNSL-SG1 trial. J Cancer Res Clin Oncol. 2017; 143(9): 1815–1821.
- Omuro AMP, Ben-Porat LS, Panageas KS, et al. Delayed neurotoxicity in primary central nervous system lymphoma. Arch Neurol. 2005; 62(10): 1595–1600.
- 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.
- Glass J, Won M, Schultz CJ, et al. Phase I and II study of induction chemotherapy with methotrexate, rituximab, and temozolomide, followed by whole-brain radiotherapy and postirradiation temozolomide for primary CNS lymphoma: NRG Oncology RTOG 0227. J Clin Oncol. 2016; 34(14): 1620–1625.
- Fisher B, Seiferheld W, Schultz C, et al. Secondary analysis of Radiation Therapy Oncology Group study (RTOG) 9310: an intergroup phase II combined modality treatment of primary central nervous system lymphoma. J Neurooncol. 2005; 74(2): 201–205.
- 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–e397.
- Alnahhas I, Jawish M, Alsawas M, et al. Autologous stem-cell transplantation for primary central nervous system lymphoma: systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2019; 19(3): e129–e141.
- 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.
- 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.