Efficacy and Safety of Various Treatment Regimens for Primary CNS Lymphoma: Results of a Retrospective Study Based on the Data from Nine Saint Petersburg Medical Institutions
DOI:
https://doi.org/10.21320/2500-2139-2026-19-3-253-263BACKGROUND. In the Russian Federation, systematic evidence of treatment outcomes and prognosis evaluation in primary CNS lymphoma (PCNSL) patients is currently unavailable.
AIM. To study the clinical and epidemiological characteristics as well as current medical practice and the first-line therapy outcomes in PCNSL patients.
MATERIALS & METHODS. The study enrolled 127 adults with histologically verified PCNSL diagnosis treated from 2010 to 2024 at nine medical institutions in Saint Petersburg. Absolute majority (n = 119; 94 %) of them received various regimens of chemo- and/or immunochemotherapy (ICT). High-dose methotrexate (HD-МТХ) protocols were administered in 103 (87 %) cases, 86 % (n = 101) of PCNSL patients received rituximab.
RESULTS. Response assessment was analyzed in 111 (87 %) patients. Objective response (OR) to the first-line therapy was 72 % (n = 80) including complete remissions in 38 (34 %) patients. With the follow-up of 12 months (range 0.4–151.1 months), the 2-year overall survival (OS) was 43 % (95 % confidence interval [95% CI] 34–54 %), and the 2-year event-free survival (EFS) was 30 % (95% CI 22–40 %). Prognostic factors included ECOG status and HD-МТХ administration. After ICT, 28 (38 %) patients with OR received radiation or high-dose therapy with autologous hematopoietic stem cell transplantation as consolidation treatment. Consolidation stage, irrespective of the chosen option, was associated with better rates of long-term survival: the 2-year OS was 78 % (95% CI 62–100 %), the 2-year EFS was 59 % (95% CI 41–84 %).
CONCLUSION. The clinical profile of PCNSL patients, as revealed in this study, is generally consistent with published literature. Most patients received the treatment regimens in accordance with the international guidelines, however, in a part of them, suboptimal treatment was used. The best rates of long-term survival were reported in patients who achieved OR and subsequently received consolidation therapy.
- Ferreri AJM, Calimeri T, Cwynarski K, et al. Primary central nervous system lymphoma. Nat Rev Dis Primers. 2023;9(1):29. doi: 10.1038/s41572-023-00439-0. DOI: https://doi.org/10.1038/s41572-023-00439-0
- Villano JL, Koshy M, Shaikh H, et al. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer. 2011;105(9):1414–8. doi: 10.1038/bjc.2011.357. DOI: https://doi.org/10.1038/bjc.2011.357
- Lebrun L, Allard-Demoustiez S, Salmon I. Pathology and new insights in central nervous system lymphomas. Curr Opin Oncol. 2023;35(5):347–56. doi: 10.1097/CCO.0000000000000978. DOI: https://doi.org/10.1097/CCO.0000000000000978
- Li M, Chen J, Wang P, et al. Clinicopathological analysis of primary central nervous system lymphoma in patients with or without HIV infection. Ann Diagn Pathol. 2024;73:152383. doi: 10.1016/j.anndiagpath.2024.152383. DOI: https://doi.org/10.1016/j.anndiagpath.2024.152383
- Kaji FA, Martinez-Calle N, Sovani V, Fox CP. Rare central nervous system lymphomas. Br J Haematol. 2022;197(6):662–78. doi: 10.1111/bjh.18128. DOI: https://doi.org/10.1111/bjh.18128
- Gandhi S, Nowakowski GS, Habermann TM, et al. Non-Diffuse Large B-Cell Primary Central Nervous System Lymphoma. Blood. 2018;132(Suppl 1):4208. doi: 10.1182/blood-2018-99-119741. DOI: https://doi.org/10.1182/blood-2018-99-119741
- Alaggio R, Amador C, Anagnostopoulos I, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022;36(7):1720–48. doi: 10.1038/s41375-022-01620-2. DOI: https://doi.org/10.1038/s41375-022-01620-2
- Ferreri AJM, Illerhaus G, Doorduijn JK, et al. Primary central nervous system lymphomas: EHA-ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. Ann Oncol. 2024:S0923-7534(23)05074-3. doi: 10.1016/j.annonc.2023.11.010. DOI: https://doi.org/10.1016/j.annonc.2023.11.010
- Fox CP, Phillips EH, Smith J, et al. Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma. Br J Haematol. 2019;184(3):348–63. doi: 10.1111/bjh.15661. DOI: https://doi.org/10.1111/bjh.15661
- NCCN Guidelines Version 1.2025. Central Nervous System Cancers. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cns.pdf. (accessed 11.03.2026).
- Агрессивные нефолликулярные лимфомы — диффузная В-клеточная крупноклеточная лимфома, В-клеточная лимфома высокой степени злокачественности с перестройкой генов c-MYC и BCL2/BCL6, первичная медиастинальная В-клеточная лимфома, медиастинальная лимфома серой зоны, лимфома Беркитта, плазмобластная лимфома. Клинические рекомендации. Национальное гематологическое общество, Российское общество онкогематологов, Ассоциация онкологов России, Национальное общество детских гематологов, онкологов, 2024. (электронный ресурс) Доступно по: https://cr.minzdrav.gov.ru/preview-cr/129_3. Ссылка активна на 11.03.2026 г. [Aggressive non-follicular lymphomas: diffuse large B-cell lymphoma, B-cell high-grade lymphoma with c-MYC и BCL2/BCL6 gene rearrangement, primary mediastinal B-cell lymphoma, mediastinal grey zone lymphoma, Burkitt lymphoma, plasmablastic lymphoma. Clinical Guidelines. National Society of Hematologists, Russian Society of Oncohematologists, Russian Oncology Association, National Society of Pediatric Hematologists and Oncologists, 2024. (Internet) Available from https://cr.minzdrav.gov.ru/preview-cr/129_3. Accessed 11.03.2026. (In Russ)]
- Abrey L, Batchelor T, Ferreri A, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol. 2005;23(22):5034–43. doi: 10.1200/JCO.2005.13.524. DOI: https://doi.org/10.1200/JCO.2005.13.524
- Abrey L, Ben-Porat L, Panageas K, et al. Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol. 2006;24(36):5711–5. doi: 10.1200/JCO.2006.08.2941. DOI: https://doi.org/10.1200/JCO.2006.08.2941
- Soussain C, Houillier C, Ghesquieres H, et al. The French LOC Network for Primary CNS Lymphoma (PCNSL) Patients: What Can We Learn from a Large National Database? Blood. 2016;128(22):926. doi: 10.1182/blood.V128.22.926.926. DOI: https://doi.org/10.1182/blood.V128.22.926.926
- Decavèle M, Dreyfus A, Gatulle N, et al. Clinical features and outcome of patients with primary central nervous system lymphoma admitted to the intensive care unit: a French national expert center experience. J Neurol. 2021;268(6):2141–50. doi: 10.1007/s00415-021-10396-x. DOI: https://doi.org/10.1007/s00415-021-10396-x
- Bairey O, Lebel E, Buxbaum C, et al. A retrospective study of 222 patients with newly diagnosed primary central nervous system lymphoma-Outcomes indicative for improved survival overtime. Hematol Oncol. 2023;41(5):838–47. doi: 10.1002/hon.3198. DOI: https://doi.org/10.1002/hon.3198
- Houillier C, Soussain C, Ghesquières H, et al. Management and outcome of primary CNS lymphoma in the modern era: An LOC network study. Neurology. 2020;94(10):e1027–e1039. doi: 10.1212/WNL.0000000000008900. DOI: https://doi.org/10.1212/WNL.0000000000008900
- Bayraktar S, Bayraktar UD, Ramos JC, et al. Primary CNS lymphoma in HIV positive and negative patients: comparison of clinical characteristics, outcome and prognostic factors. J Neurooncol. 2011;101(2):257–65. doi: 10.1007/s11060-010-0252-3. DOI: https://doi.org/10.1007/s11060-010-0252-3
- Nien JE, Chuang CC, Hsu PW, et al. The impact of tumor resection on survival and functional outcomes for patients with primary central nervous system lymphoma. Clin Neurol Neurosurg. 2024;246:108551. doi: 10.1016/j.clineuro.2024.108551. DOI: https://doi.org/10.1016/j.clineuro.2024.108551
- Wu S, Wang J, Liu W, et al. The role of surgical resection in primary central nervous system lymphoma: a single-center retrospective analysis of 70 patients. BMC Neurol. 2021;21(1):190. doi: 10.1186/s12883-021-02227-3. DOI: https://doi.org/10.1186/s12883-021-02227-3
- Herrlinger U, Küker W, Uhl M, et al. NOA-03 trial of high-dose methotrexate in primary central nervous system lymphoma: final report. Ann Neurol. 2005;57(6):843–7. doi: 10.1002/ana.20495. DOI: https://doi.org/10.1002/ana.20495
- Batchelor T, Carson K, O’Neill A, et al. Treatment of primary CNS lymphoma with methotrexate and deferred radiotherapy: a report of NABTT 96-07. J Clin Oncol. 2003;21(6):1044–9. doi: 10.1200/JCO.2003.03.036. DOI: https://doi.org/10.1200/JCO.2003.03.036
- Ferreri AJ, Reni M, Foppoli M, et al. 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):1512–20. doi: 10.1016/S0140-6736(09)61416-1. DOI: https://doi.org/10.1016/S0140-6736(09)61416-1
- Cobert J, Hochberg E, Woldenberg N, Hochberg F. Monotherapy with methotrexate for primary central nervous lymphoma has single agent activity in the absence of radiotherapy: a single institution cohort. J Neurooncol. 2010;98(3):385–93. doi: 10.1007/s11060-009-0090-3. DOI: https://doi.org/10.1007/s11060-009-0090-3
- Ferreri AJM, Cwynarski K, Pulczynski E, et al. Long-term efficacy, safety and neurotolerability of MATRix regimen followed by autologous transplant in primary CNS lymphoma: 7-year results of the IELSG32 randomized trial. Leukemia. 2022;36(7):1870–8. doi: 10.1038/s41375-022-01582-5. DOI: https://doi.org/10.1038/s41375-022-01582-5
- Fallah J, Qunaj L, Olszewski AJ. Therapy and outcomes of primary central nervous system lymphoma in the United States: analysis of the National Cancer Database. Blood Adv. 2016;1(2):112–21. doi: 10.1182/bloodadvances.2016000927. DOI: https://doi.org/10.1182/bloodadvances.2016000927
- 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. doi: 10.1016/0360-3016(92)90538-s. DOI: https://doi.org/10.1016/0360-3016(92)90538-S
- Kurzwelly D, Glas M, Roth P, et al. Primary CNS lymphoma in the elderly: temozolomide therapy and MGMT status. J Neurooncol. 2010;97(3):389–92. doi: 10.1007/s11060-009-0032-0. DOI: https://doi.org/10.1007/s11060-009-0032-0
- Jaradat JH, Alkhawaldeh IM, Al-Bojoq Y, et al. Efficacy and safety of ibrutinib in central nervous system lymphoma: A systematic review and meta-analysis. Crit Rev Oncol Hematol. 2025;206:104597. doi: 10.1016/j.critrevonc.2024.104597. DOI: https://doi.org/10.1016/j.critrevonc.2024.104597
- Gavrilenko А, Markelov V, Volkov N, et al. Nivolumab-based therapy of relapsed or refractory primary large B-cell lymphoma of immune-privileged sites and DLBCL with secondary CNS involvement. HemaSphere. 2023;7(Suppl):e49127b4. doi: 10.1097/01.HS9.0000975956.49127.b4. DOI: https://doi.org/10.1097/01.HS9.0000975956.49127.b4
- Zeng Z, Yang A, Yang J, et al. Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study. Signal Transduct Target Ther. 2024;9(1):229. doi: 10.1038/s41392-024-01941-x. DOI: https://doi.org/10.1038/s41392-024-01941-x
- 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):621–8. doi: 10.1093/annonc/mdz032. DOI: https://doi.org/10.1093/annonc/mdz032
- Godfrey JK, Gao L, Shouse G, et al. Glofitamab stimulates immune cell infiltration of CNS tumors and induces clinical responses in secondary CNS lymphoma. Blood. 2024;144(4):457–61. doi: 10.1182/blood.2024024168. DOI: https://doi.org/10.1182/blood.2024024168
- Cook MR, Dorris CS, Makambi KH, et al. Toxicity and efficacy of CAR T-cell therapy in primary and secondary CNS lymphoma: a meta-analysis of 128 patients. Blood Adv. 2023;7(1):32–9. doi: 10.1182/bloodadvances.2022008525. DOI: https://doi.org/10.1182/bloodadvances.2022008525
- Звонков Е.Е., Королева Д.А., Габеева Н.Г. и др. Первый опыт терапии больных первичной диффузной В-крупноклеточной лимфомой центральной нервной системы (ПДВККЛ ЦНС) по протоколу «CNS-2021». Гематология и трансфузиология. 2022;67(2):203–4. [Zvonkov E.E., Koroleva D.A., Gabeeva N.G., et al. First experience of therapy for primary diffuse large B-cell lymphoma of the central nervous system (PDLBCL CNS) according to the CNS-2021 protocol. Gematologiya i transfuziologiya. 2022;67(2):203–4. (In Russ)]
- Rubenstein JL, Combs D, Rosenberg J, et al. Rituximab therapy for CNS lymphomas: targeting the leptomeningeal compartment. Blood. 2003;101(2):466–8. doi: 10.1182/blood-2002-06-1636. DOI: https://doi.org/10.1182/blood-2002-06-1636
- Shah GD, Yahalom J, Correa DD, et al. Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol. 2007;25(30):4730–5. doi: 10.1200/JCO.2007.12.5062. DOI: https://doi.org/10.1200/JCO.2007.12.5062
- 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):216–28. doi: 10.1016/S1470-2045(18)30747-2. DOI: https://doi.org/10.1016/S1470-2045(18)30747-2
- Bromberg JEC, Issa S, van der Holt B, et al. Survival, neurocognitive function, and health-related quality of life outcomes after rituximab-methotrexate, BCNU, teniposide, and prednisolone for primary CNS lymphoma: Final results of the HOVON 105/ALLG NHL 24 study. Neuro Oncol. 2024;26(4):724–34. doi: 10.1093/neuonc/noad224. DOI: https://doi.org/10.1093/neuonc/noad224
- 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):548–57. doi: 10.1002/hon.2666. DOI: https://doi.org/10.1002/hon.2666
- Zhang Y, Liu Z, Gao C, et al. Role of Rituximab in Treatment of Patients With Primary Central Nervous System Lymphoma (PCNSL): A Systematic Review and Meta-Analysis. Clin Lymphoma Myeloma Leuk. 2023;23(10):733–41. doi: 10.1016/j.clml.2023.06.008. DOI: https://doi.org/10.1016/j.clml.2023.06.008
- Batchelor TT, Giri S, Ruppert AS, et al. Myeloablative vs nonmyeloablative consolidation for primary central nervous system lymphoma: results of Alliance 51101. Blood Adv. 2024;8(12):3189–99. doi: 10.1182/bloodadvances.2023011657. DOI: https://doi.org/10.1182/bloodadvances.2023011657
- Groot FAD, Doorduijn JK, Brink M, et al. Consolidation Improves Survival in Primary Central Nervous System Lymphoma without Preference for Type of High-Dose Methotrexate-Based Induction Treatment Regimen. Blood. 2022;140(Suppl 1):369–71. doi: 10.1182/blood-2022-163244. DOI: https://doi.org/10.1182/blood-2022-163244
- Houillier C, Dureau S, Taillandier L, et al. Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study. J Clin Oncol. 2022;40(32):3692–8. doi: 10.1200/JCO.22.00491. DOI: https://doi.org/10.1200/JCO.22.00491
Keywords:
primary CNS lymphoma, therapy, autologous hematopoietic stem cell transplantation, radiation therapy
License
Copyright (c) 2026 Clinical Oncohematology. Basic Research and Clinical Practice

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.






























