Orelabrutinib combined with rituximab and high-dose methotrexate as induction therapy in newly diagnosed primary central nervous system lymphoma

Hoang-Xuan K, Deckert M, Ferreri AJM, Furtner J, Gallego Perez-Larraya J, Henriksson R, Hottinger AF, Kasenda B, Lefranc F, Lossos A et al (2023) European association of neuro-oncology (EANO) guidelines for treatment of primary central nervous system lymphoma (PCNSL). Neuro Oncol 25:37–53. https://doi.org/10.1093/neuonc/noac196

Article  CAS  PubMed  Google Scholar 

Kerbauy MN, Moraes FY, Lok BH, Ma J, Kerbauy LN, Spratt DE, Santos FP, Perini GF, Berlin A, Chung C et al (2017) Challenges and opportunities in primary CNS lymphoma: a systematic review. Radiother Oncol 122:352–361. https://doi.org/10.1016/j.radonc.2016.12.033

Article  PubMed  Google Scholar 

Ferreri AJ, Calimeri T, Cwynarski K, Dietrich J, Grommes C, Hoang-Xuan K, Hu LS, Illerhaus G, Nayak L, Ponzoni M (2023) Primary central nervous system lymphoma. Nat Rev Dis Primers 9:29

Article  PubMed  PubMed Central  Google Scholar 

Ferreri AJ, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F (2009) High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. The Lancet 374:1512–1520

Article  CAS  Google Scholar 

Ferreri AJ, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, La Rosée P, Schorb E (2016) 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. The Lancet Haematology 3:e217–e227

Article  PubMed  Google Scholar 

Zhang Y, Ye J, Chen H, Zhou D, Ji C (2024) Efficacy and safety of BTKis in central nervous system lymphoma: a systematic review and meta-analysis. Cancers 16:860

Article  CAS  PubMed  PubMed Central  Google Scholar 

Grommes C, Nayak L, Tun HW, Batchelor TT (2019) Introduction of novel agents in the treatment of primary CNS lymphoma. Neuro Oncol 21:306–313. https://doi.org/10.1093/neuonc/noy193

Article  PubMed  Google Scholar 

Wen T, Wang J, Shi Y, Qian H, Liu P (2021) Inhibitors targeting Bruton’s tyrosine kinase in cancers: drug development advances. Leukemia 35:312–332. https://doi.org/10.1038/s41375-020-01072-6

Article  CAS  PubMed  Google Scholar 

Nepal G, Khurana M, Bucheli DH, Bhandari S, Joshi U, Bhagat R, Rehrig JH, Pudasainee P, Shing YK, Ortiz JF (2022) Ibrutinib in refractory or relapsing primary central nervous system lymphoma: a systematic review. Neurol Int 14:99–108

Article  CAS  PubMed  PubMed Central  Google Scholar 

Guo Y, Shan Y, Chang X, Zou D, Ma Q, Wei Y, Xu G, Wang Y, Tang J, Wang D (2024) Ibrutinib, rituximab, and high-dose methotrexate in newly diagnosed primary diffuse large B-cell lymphoma of the CNS: a prospective, phase II, single-arm, single-center study. Blood 144:6539

Article  Google Scholar 

Gao Y, Ping L, Shan C, Huang H, Li Z, Zhou H, Lai M, Cai L, Bai B, Huang C (2025) High-dose methotrexate, ibrutinib, and temozolomide in the treatment of newly diagnosed primary CNS lymphoma: a multicenter, prospective phase-II study. Blood Cancer Discov 6:191–202

Article  PubMed  PubMed Central  Google Scholar 

Ran F, Liu Y, Wang C, Xu Z, Zhang Y, Liu Y, Zhao G, Ling Y (2022) Review of the development of BTK inhibitors in overcoming the clinical limitations of ibrutinib. Eur J Med Chem 229:114009

Article  CAS  PubMed  Google Scholar 

Fürstenau M, Simon F, Cornely OA, Hicketier T, Eichhorst B, Hallek M, Mellinghoff SC (2020) Invasive aspergillosis in patients treated with ibrutinib. HemaSphere 4:e309

Article  PubMed  PubMed Central  Google Scholar 

Robak P, Witkowska M, Wolska-Washer A, Robak T (2023) The preclinical discovery and development of orelabrutinib as a novel treatment option for B-cell lymphoid malignancies. Expert Opin Drug Discov 18:1065–1076

Article  CAS  PubMed  Google Scholar 

Deng L, Li Z, Zhang H, Huang H, Hu J, Liu L, Liu T, Jin J, Zhu Z, Li W et al (2023) Orelabrutinib for the treatment of relapsed or refractory marginal zone lymphoma: a phase 2, multicenter, open-label study. Am J Hematol 98:1742–1750. https://doi.org/10.1002/ajh.27064

Article  CAS  PubMed  Google Scholar 

Zhang Y, Wang W, Zhao D, Zhang W, Zhou D (2022) S224: preliminary results of a phase II study of orelabrutinib in combination with anti-PD-1 monoclonal antibody in refractory or relapsed primary CNS lymphoma. HemaSphere 6:125–126

Article  Google Scholar 

Xia Y, Cai Q, Zhang P, Tian X, Fang X (2024) Orelabrutinib, rituximab, temozolomide and high-dose methotrexate (RMOT) in newly diagnosed primary central nervous system lymphoma (PCNSL): a retrospective analysis on efficacy and safety. Am Soc Clin Oncol 42:e19041

Article  Google Scholar 

Sheng L, Ouyang G, Lai Y, Nie S, Wang D, Tang S, Pan Y, Xu K, Sun Y, Zhang P (2024) Preliminary data on the efficacy and safety of orelabrutinib combined with rituximab and methotrexate (ORM regimen) as first-line treatment for primary central nervous system lymphoma, and the exploration of cerebrospinal fluid Ctdna dynamic monitoring. Blood 144:4500

Article  Google Scholar 

Yang C, Cui Y, Ren X, Li M, Yu K, Shen S, Jiang H, Li M, Zhang X, Zhao X et al (2022) Orelabrutinib combined with lenalidomide and immunochemotherapy for relapsed/refractory primary central nervous system lymphoma: a retrospective analysis of case series. Front Oncol 12:901797. https://doi.org/10.3389/fonc.2022.901797

Article  CAS  PubMed  PubMed Central  Google Scholar 

Joerger M, Huitema A, Krähenbühl S, Schellens J, Cerny T, Reni M, Zucca E, Cavalli F, Ferreri A (2010) Methotrexate area under the curve is an important outcome predictor in patients with primary CNS lymphoma: a pharmacokinetic–pharmacodynamic analysis from the IELSG no. 20 trial. Br J Cancer 102:673–677

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schorb E, Fox CP, Kasenda B, Linton K, Martinez-Calle N, Calimeri T, Ninkovic S, Eyre TA, Cummin T, Smith J (2020) Induction therapy with the MATRix regimen in patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system–an international study of feasibility and efficacy in routine clinical practice. Br J Haematol 189:879–887

Article  CAS  PubMed  Google Scholar 

Grommes C, Tang SS, Wolfe J, Kaley TJ, Daras M, Pentsova EI, Piotrowski AF, Stone J, Lin A, Nolan CP (2019) Phase 1b trial of an ibrutinib-based combination therapy in recurrent/refractory CNS lymphoma. Blood, J Am Soc Hematol 133:436–445

CAS  Google Scholar 

Xiao X, Chen P, Jiang H, Li X, Xie J, Qian W (2024) Zanubrutinib in combination with R-MTX for newly diagnosed primary central nervous system lymphoma. Blood 144:6484

Article  Google Scholar 

Fritsch K, Kasenda B, Hader C, Nikkhah G, Prinz M, Haug V, Haug S, Ihorst G, Finke J, Illerhaus G (2011) Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann Oncol 22:2080–2085

Article  CAS  PubMed  Google Scholar 

Wu J-J, Wang W-H, Dong M, Ma S-S, Zhang X-D, Zhu L-N, Niu S-T, Ding M-J, Zhang J-M, Zhang L (2022) Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study. Invest New Drugs 40:650–659

Article  CAS  PubMed  Google Scholar 

Yu H, Wang X, Li J, Ye Y, Wang D, Fang W, Mi L, Ding N, Wang X, Song Y (2021) Addition of BTK inhibitor orelabrutinib to rituximab improved anti-tumor effects in B cell lymphoma. Mol Ther-oncolytics 21:158–170

Article  CAS  PubMed  PubMed Central  Google Scholar 

Xu W, Zhou K, Wang T, Yang S, Liu L, Hu Y, Zhang W, Ding K, Zhou J, Gao S (2023) Orelabrutinib in relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma patients: multi-center, single-arm, open-label, phase 2 study. Am J Hematol 98:571–579

Article  CAS  PubMed  Google Scholar 

Zhong K, Shi Y, Gao Y, Zhang H, Zhang M, Zhang Q, Cen X, Xue M, Qin Y, Zhao Y (2023) First-line induction chemotherapy with high-dose methotrexate versus teniposide in patients with newly diagnosed primary central nervous system lymphoma: a retrospective, multicenter cohort study. BMC Cancer 23:746

Article  CAS  PubMed  PubMed Central  Google Scholar 

Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, O’Brien S, Yenerel MN, Illés A, Kay N et al (2021) Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol 39:3441–3452. https://doi.org/10.1200/jco.21.01210

Article  CAS  PubMed 

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