Bruton Tyrosine Kinase Inhibitors for the Treatment of Relapsed Mantle Cell Lymphoma Involving CNS: Two Case Reports and Literature Review

Evgenii Olegovich Kunevich, N.N. Nemstsveridze, M.A. Mikhaleva, A.Yu. Kuvshinov, T.V. Ovchinnikova, E.V. Koryakina, S.V. Samarina, K.Yu. Krutikova, S.V. Sidorkevich, S.V. Voloshin,

DOI:

https://doi.org/10.21320/2500-2139-2025-18-2-184-196

Mantle cell lymphoma (MCL) accounts for 3–10 % of all non-Hodgkin lymphoma variants and is characterized by its aggressive course with frequent relapses and extranodal lesions. Due to more effective systemic chemotherapy and, as a consequence of this, increased life expectancy, relapse rate in MCL involving CNS, according to the literature, has increased to 4–20 %. Despite widespread introduction of targeted drugs into clinical practice, the prognosis in patients with CNS lesions remains extremely poor. This paper concentrates on the feasibility of Bruton tyrosine kinase (BTK) inhibitors for the treatment of relapsed MCL involving CNS. The most commonly recommended drug is ibrutinib, as it penetrates the blood-brain barrier and possesses high antitumor activity. Our own experience with ibrutinib in the treatment of MCL neurorelapses is illustrated in two case reports. In parallel, a comprehensive analysis focuses on the relevant literature data. Besides, this study used the data from 67 MCL patients treated at hematology hospitals of various medical institutions in Saint Petersburg and the Leningrad Region from 2006 to 2023. The reports on two clinical cases were made in compliance with the international CARE guidelines for case reports, 2017.

  1. Alaggio R, Amador C, Anagnostopoulos I. 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
  2. Pérez-Galán P, Dreyling M, Wiestne A. Mantle cell lymphoma: biology, pathogenesis, and the molecular basis of treatment in the genomic era. Blood. 2011;117(1):26–38. doi: 10.1182/blood-2010-04-189977. DOI: https://doi.org/10.1182/blood-2010-04-189977
  3. Bertoni F, Rinaldi A, Zucca E, et al. Update on the molecular biology of mantle cell lymphoma. Hematol Oncol. 2006;4(1):22–7. doi: 10.1002/hon.767. DOI: https://doi.org/10.1002/hon.767
  4. Zucca E, Roggero E, Pinotti G, et al. Patterns of survival in mantle cell lymphoma. Ann Oncol. 1995;6(3):257–62. doi: 10.1093/oxfordjournals.annonc.a059155. DOI: https://doi.org/10.1093/oxfordjournals.annonc.a059155
  5. Ghielmini M, Zucca E. How I treat mantle cell lymphoma. Blood. 2009;114(8):1469–76. doi: 10.1182/blood-2009-02-179739. DOI: https://doi.org/10.1182/blood-2009-02-179739
  6. Montserrat E, Bosch F, López-Guillermo A, et al. CNS involvement in mantle-cell lymphoma. J Clin Oncol. 1996;14(3):941–4. doi: 10.1200/JCO.1996.14.3.941. DOI: https://doi.org/10.1200/JCO.1996.14.3.941
  7. Cheah CY, George A, Giné E, et al. Central nervous system involvement in mantle cell lymphoma: clinical features, prognostic factors and outcomes from the European Mantle Cell Lymphoma Network. Ann Oncol. 2013;24(8):2119–23. doi: 10.1093/annonc/mdt139. DOI: https://doi.org/10.1093/annonc/mdt139
  8. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507–16. doi: 10.1056/NEJMoa1306220. DOI: https://doi.org/10.1056/NEJMoa1306220
  9. Lewis KL, Chin CK, Manos K, et al. Ibrutinib for central nervous system lymphoma: the Australasian Lymphoma Alliance/MD Anderson Cancer Center experience. Br J Haematol. 2021;192(6):1049–53. doi: 10.1111/bjh.16946. DOI: https://doi.org/10.1111/bjh.16946
  10. Клеина Е.В. Генетическая стратификация и особенности клинического течения мантийноклеточной лимфомы: Дис. … канд. мед. наук. СПб., 2023. 174 с. [Kleina E.V. Geneticheskaya stratifikatsiya i osobennosti klinicheskogo techeniya mantiinokletochnoi limfomy. (Genetic stratification and clinical features of mantle cell lymphoma.) [dissertation] Saint Petersburg; 2023. 174 p. (In Russ)]
  11. Riley DS, Barber MS, Kienle GS, et al. CARE guidelines for case reports: explanation and elaboration document. J Clin Epidemiol. 2017;89:218–35. doi: 10.1016/j.jclinepi.2017.04.026. DOI: https://doi.org/10.1016/j.jclinepi.2017.04.026
  12. Bedotto J, Spier CM, Paquin ML, et al. Mantle zone lymphoma with central nervous system involvement. Cancer. 1986;58(9):2125–9. doi: 10.1002/1097-0142(19861101)58:9<2125::aid-cncr2820580927>3.0.co;2-t. DOI: https://doi.org/10.1002/1097-0142(19861101)58:9<2125::AID-CNCR2820580927>3.0.CO;2-T
  13. Ellison DJ, Turner RR, Van AR, et al. High-grade mantle zone lymphoma. Cancer. 1987;60(7):2717–20. doi: 10.1002/1097-0142(19820401)49:7<1429::aid-cncr2820490720>3.0.co;2-5. DOI: https://doi.org/10.1002/1097-0142(19871201)60:11<2717::AID-CNCR2820601123>3.0.CO;2-K
  14. Segal GH, Masih AS, Fox AC, et al. CD5-expressing B-cell non-Hodgkin’s lymphomas with bcl-1 gene rearrangement have a relatively homogeneous immunophenotype and are associated with an overall poor prognosis. Blood. 1995;85(6):1570–9. doi: 10.1182/blood.V85.6.1570.bloodjournal8561570. DOI: https://doi.org/10.1182/blood.V85.6.1570.bloodjournal8561570
  15. Gagneten D, Hijazi YM, Jaffe ES, et al. Mantle cell lymphoma: a cytopathological and immunocytochemical study. Diagnostic Cytopathol. 1996;14(1):32–7. doi: 10.1002/(SICI)1097-0339(199602)14:1<32::AID-DC7>3.0.CO;2-X. DOI: https://doi.org/10.1002/(SICI)1097-0339(199602)14:1<32::AID-DC7>3.0.CO;2-X
  16. Kaleem Z, Wakoff AR, Smith RP, Hess JL. Blastic transformation of mantle cell lymphoma. Arch Pathol Lab Med. 1996;120(6):577–80.
  17. Finsterer J, Lubec D, Jellinger K, et al. Recovery from coma caused by primary CNS mantle cell lymphoma presenting as encephalitis. Neurology. 1996;46(3):824–6. doi: 10.1212/wnl.46.3.824. DOI: https://doi.org/10.1212/WNL.46.3.824
  18. Bosch F, López-Guillermo A, Campo E, et al. Mantle cell lymphoma: presenting features, response to therapy, and prognostic factors. Cancer. 1998;82(3):567–75. doi: 10.1002/(sici)1097-0142(19980201)82:3<567::aid-cncr20>3.0.co;2-z. DOI: https://doi.org/10.1002/(SICI)1097-0142(19980201)82:3<567::AID-CNCR20>3.0.CO;2-Z
  19. Oinonen R, Franssila K, Elonen E. Central nervous system involvement in patients with mantle cell lymphoma. Ann Hematol. 1999;78(3):145–9. doi: 10.1007/s002770050491. DOI: https://doi.org/10.1007/s002770050491
  20. Valdez R, Kroft SH, Ross CW, et al. Cerebrospinal fluid involvement in mantle cell lymphoma. Mod Pathol. 2002;15(10):1073–9. doi: 10.1097/01.MP.0000030088.28684.5B. DOI: https://doi.org/10.1097/01.MP.0000030088.28684.5B
  21. Trip SA, Wroe SJ, Davies G, et al. Primary CNS mantle cell lymphoma associated with an isolated CSF monoclonal IgG band. Eur Neurol. 2003;49(3):187–8. doi: 10.1159/000069080. DOI: https://doi.org/10.1159/000069080
  22. Ladetto M, Sametti S, Astolfi M, et al. Central nervous system relapse in a patient with mantle cell lymphoma in continuous clinical and molecular remission at six years since autografting. Leuk Lymphoma. 2001;40(5–6):679–82. doi: 10.3109/10428190109097668. DOI: https://doi.org/10.3109/10428190109097668
  23. Pachmann S, Bruning R, Schaffer M, et al. Suboccipital lateral injection of intrathecal chemotherapy in a patient with mantle cell lymphoma. Onkologie. 2004;27(1):68–71. doi: 10.1159/000075609. DOI: https://doi.org/10.1159/000075609
  24. Ferrer A, Bosch F, Villamor N, et al. Central nervous system involvement in mantle cell lymphoma. Ann Oncol. 2008;19(1):135–41. doi: 10.1093/annonc/mdm447. DOI: https://doi.org/10.1093/annonc/mdm447
  25. Dierickx D, Wlodarska I, Vanhentenrijk V, et al. Secondary central nervous system involvement in cyclin D1-negative mantle cell lymphoma. Leuk Lymphoma. 2008;49(12):2365–6. doi: 10.1080/10428190802464737. DOI: https://doi.org/10.1080/10428190802464737
  26. Wlodarska I, Dierickx D, Vanhentenrijk V, et al. Translocations targeting CCND2, CCND3, and MYCN do occur in t(11;14)-negative mantle cell lymphomas. Blood. 2008;111(12):5683–90. doi: 10.1182/blood-2007-10-118794. DOI: https://doi.org/10.1182/blood-2007-10-118794
  27. Gill S, Herbert KE, Prince HM, et al. Mantle cell lymphoma with central nervous system involvement: frequency and clinical features. Br J Haematol. 2009;14(1):83–8. doi: 10.1111/j.1365-2141.2009.07835.x. DOI: https://doi.org/10.1111/j.1365-2141.2009.07835.x
  28. Gurevitz SA, Goldfarb JM, Cooper B, et al. Biopsy-proven mantle cell lymphoma in brain parenchyma. Proc (Bayl Univ Med Cent). 2011;24(1):45–7. doi: 10.1080/08998280.2011.11928681. DOI: https://doi.org/10.1080/08998280.2011.11928681
  29. Doolittle ND, Abrey LE, Shenkier TN, et al. Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report. Blood. 2008;111(3):1085–93. doi: 10.1182/blood-2007-07-101402. DOI: https://doi.org/10.1182/blood-2007-07-101402
  30. Conconi A, Franceschetti S, Lobetti-Bodoni C, et al. Risk factors of central nervous system relapse in mantle cell lymphoma. Lymphoma. 2013;54(9):1908–14. doi: 10.3109/10428194.2013.767454. DOI: https://doi.org/10.3109/10428194.2013.767454
  31. Chihara D, Asano N, Ohmachi K, et al. Ki-67 is a strong predictor of central nervous system relapse in patients with mantle cell lymphoma (MCL). Ann Oncol. 2015;26(5):966–73. doi: 10.1093/annonc/mdv074. DOI: https://doi.org/10.1093/annonc/mdv074
  32. Wang ML, Blum KA, Martin P, et al. Long-term follow-up of MCL patients treated with single-agent ibrutinib: updated safety and efficacy results. Blood. 2015;126(6):739–45. doi: 10.1182/blood-2015-03-635326. DOI: https://doi.org/10.1182/blood-2015-03-635326
  33. Dreyling M, Jurczak W, Jerkeman M, et al. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016;387(10020):770–8. doi: 10.1016/S0140-6736(15)00667-4. DOI: https://doi.org/10.1016/S0140-6736(15)00667-4
  34. Rule S, Jurczak W, Jerkeman M, et al. Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study. Leukemia. 2018;32(8):1799–803. doi: 10.1038/s41375-018-0023-2. DOI: https://doi.org/10.1038/s41375-018-0023-2
  35. Bernard S, Goldwirt L, Amorim S, et al. Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. Blood. 2015;126(14):1695–8. doi: 10.1182/blood-2015-05-647834. DOI: https://doi.org/10.1182/blood-2015-05-647834
  36. Dunleavy K, Lai CE, Roschewski M, et al. Phase I Study of Dose-Adjusted-Teddi-R with ibrutinib in untreated and relapsed/refractory primary CNS lymphoma. Blood. 2015;126(23):472. doi: 10.1182/blood.V126.23.472.472. DOI: https://doi.org/10.1182/blood.V126.23.472.472
  37. FDA. Clinical Pharmacology Reviews Ibrutinib 205552Orig1s000. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/205552orig1s000clinpharmr.pdf (accessed 30.09.2024).
  38. Mason C, Savona S, Rini JN, et al. Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome [letter]. Br J Haematol. 2016;179(2):339–41. doi: 10.1111/bjh.14218. DOI: https://doi.org/10.1111/bjh.14218
  39. Tucker DL, Naylor G, Kruger A, et al. Ibrutinib is a safe and effective therapy for systemic mantle cell lymphoma with central nervous system involvement – a multi-centre case series from the United Kingdom. Br J Haematol. 2017;178(2):327–9. doi: 10.1111/bjh.14122. DOI: https://doi.org/10.1111/bjh.14122
  40. Mannina D, Loteta B. Ibrutinib treatment of mantle cell lymphoma relapsing at central nervous system: A Case Report and Literature Review. Case Rep Hematol. 2017;2017:9583257. doi: 10.1155/2017/9583257. DOI: https://doi.org/10.1155/2017/9583257
  41. González-Bonet LG, García-Boyero R, Gaona-Morales J. Mantle cell lymphoma with central nervous system involvement simulating bilateral subdural hematomas. World Neurosurg. 2017;99:808. doi: 10.1016/j.wneu.2016.12.122. DOI: https://doi.org/10.1016/j.wneu.2016.12.122
  42. Shaikh H, Jani P, Shah R, et al. Mantle cell lymphoma relapsing as disease of skin, orbit and CNS: an extremely rare presentation and a review of literature. J Hematol. 2018;7(1):38–42. doi: 10.14740/jh363w. DOI: https://doi.org/10.14740/jh363w
  43. Vitagliano O, Trastulli F, Cacace F, et al. Ibrutinib as salvage therapy in mantle cell lymphoma with central nervous system involvement in a pretreated unfit patient. Leuk Lymphoma. 2018;59(7):1734–7. doi: 10.1080/10428194.2017.1387910. DOI: https://doi.org/10.1080/10428194.2017.1387910
  44. Alsuliman T, Belghoul M, Choufi B. Ibrutinib treatment through nasogastric tube in a comatose patient with central nervous system localization of mantle cell lymphoma. Case Rep Hematol. 2018;2018:5761627. doi: 10.1155/2018/5761627. DOI: https://doi.org/10.1155/2018/5761627
  45. Okahashi N, Uchihara M, Hoshino E. Mantle cell lymphoma with central nervous system relapse successfully treated with nasogastric-tube administration of ibrutinib. Rinsho Ketsueki. 2020;61(10):1508–10. doi: 10.11406/rinketsu.61.1508.
  46. Nakamura M, Iwasa H, Kojima K. Central nervous system involvement in mantle cell lymphoma presenting magnetic resonance imaging features of mild encephalitis/encephalopathy with a reversible splenial lesion. Intern Med. 2021;60(10):1597–600. doi: 10.2169/internalmedicine.6386-20. DOI: https://doi.org/10.2169/internalmedicine.6386-20
  47. Ağargün BF, Özbalak M, Gülseren UA, et al. Central nervous system involvement of mantle cell lymphoma: Case report and review of the literature. Hematol Transfus Cell Ther. 2024;46(Suppl 6):S367–S372. doi: 10.1016/j.htct.2022.10.002. DOI: https://doi.org/10.1016/j.htct.2022.10.002
  48. Myers AL, Kawedia JD, Nader A, et al. A rare case of methotrexate and primaquine co-administration in a mantle cell lymphoma patient. J Clin Pharm Ther. 2019;44(5):800–4. doi: 10.1111/jcpt.12849. DOI: https://doi.org/10.1111/jcpt.12849
  49. Rich JD, Clark SM, Fedoriw Y, et al. Complete remission with ibrutinib after allogeneic stem cell transplant for central nervous system relapse of mantle cell lymphoma: A case report and literature review. Clin Case Rep. 2019;7(10):1957–61. doi: 10.1002/ccr3.2257. DOI: https://doi.org/10.1002/ccr3.2257
  50. Fukushima N, Mino T, Arihiro K, Ichinohe T. Cooccurrence of CD10-Positive and CD10-Negative Mantle Cell Lymphoma Complicated With Central Nervous System Involvement Solely by CD10-Positive Population. Cureus. 2022;14(1):e21341. doi: 10.7759/cureus.21341. DOI: https://doi.org/10.7759/cureus.21341
  51. Rusconi C, Cheah CY, Tucker D, et al. Ibrutinib Compared to Immune-Chemotherapy for Central Nervous System Relapse of Mantle Cell Lymphoma: A Report from Fondazione Italiana Linfomi (FIL) and European Mantle Cell Lymphoma Network (EMCLN). HemaSphere. 2020;4(1):73–7. doi: 10.1182/blood.2022015560.
  52. Hansen MH, Juul-Jensen K, Cédile O, et al. Distal chromosome 1q aberrations and initial response to ibrutinib in central nervous system relapsed mantle cell lymphoma. Leuk Res Rep. 2021;15:100255. doi: 10.1016/j.lrr.2021.100255. DOI: https://doi.org/10.1016/j.lrr.2021.100255
  53. Oh TS, Burkart M, Behdad A, et al. Ibrutinib plus R-ICE induces remission in blastoid variant mantle cell lymphoma with CNS relapse. Case Rep Hematol. 2022;2022:1930546. doi: 10.1155/2022/1930546. DOI: https://doi.org/10.1155/2022/1930546
  54. Rusconi C, Cheah CY, Eyre TA, et al. Ibrutinib improves survival compared to chemotherapy in mantle cell lymphoma with central nervous system relapse. Blood. 2022;140(17):1907–16. doi: 10.1182/blood.2022015560. DOI: https://doi.org/10.1182/blood.2022015560
  55. McLaughlin N, Wang Y, Inwards DJ, et al. Outcomes in mantle cell lymphoma with central nervous system involvement. J Clin Oncol. 2021;39(15): Abstract e19527. DOI: https://doi.org/10.1200/JCO.2021.39.15_suppl.e19527
  56. McLaughlin N, Wang Y, Witzig T, et al. Central nervous system involvement by mantle cell lymphoma. Leuk Lymphoma. 2023;64(2):371–7. doi: 10.1080/10428194.2022.2148211. DOI: https://doi.org/10.1080/10428194.2022.2148211
  57. McLaughlin N, Joseph A, Wang Y, et al. Outcomes in Mantle Cell Lymphoma with Central Nervous System Involvement–a Dual Center Study. Blood. 2023;142(1):1670. doi: 10.1182/blood-2023-174701. DOI: https://doi.org/10.1182/blood-2023-174701
  58. Vu K, Frank MJ. CAR T-cell therapy for mantle cell lymphoma with central nervous system relapse. Blood Adv. 2023;7(3):375–8. doi: 10.1182/bloodadvances.2022008031. DOI: https://doi.org/10.1182/bloodadvances.2022008031
  59. Rai M, Maziarz R, Ratterree B, et al. Relapsed mantle cell lymphoma with parenchymal central nervous system involvement successfully treated with chimeric antigen receptor T-cell therapy—a case report. Ann Lymphoma. 2024;8:1–6. doi: 10.21037/aol-23-22. DOI: https://doi.org/10.21037/aol-23-22
  60. Chappelow AV, Singh AD, Perez VL, et al. Bilateral panocular involvement with mantle-cell lymphoma. J Clin Oncol. 2008;26(7):1167. doi: 10.1200/JCO.2007.14.2620. DOI: https://doi.org/10.1200/JCO.2007.14.2620
  61. Aldrees, S, Jeeva-Patel T, Margolin E. Bilateral infiltrative optic neuropathy of systemic mantle cell lymphoma. Can J Neurol Sci. 2020;47(3):428–30. doi: 10.1017/cjn.2020.28. DOI: https://doi.org/10.1017/cjn.2020.28
  62. Small L, Ma C, Shah M et al. Bilateral vision loss as the initial presentation for central nervous system involvement of mantle cell lymphoma: A case series. Am J Ophthalmol Case Rep. 2021;23:101131. doi: 10.1016/j.ajoc.2021.101131. DOI: https://doi.org/10.1016/j.ajoc.2021.101131
  63. Singer JR, Nigalye AK, Champion MT, Welch MJ. Intravitreal methotrexate for mantle cell lymphoma infiltration of the optic nerves: a case report. Retin Cases Brief Rep. 2018;12(1):5–9. doi: 10.1097/ICB.0000000000000385. DOI: https://doi.org/10.1097/ICB.0000000000000385
  64. Jain P, Zhang S, Kanagal-Shamanna R, et al. Genomic profiles and clinical outcomes of de novo blastoid/pleomorphic MCL are distinct from those of transformed MCL. Blood Adv. 2020;4(6):1038–50. doi: 10.1182/bloodadvances.2019001396. DOI: https://doi.org/10.1182/bloodadvances.2019001396
  65. Fischer L, Korfel A, Pfeiffer S, et al CXCL13 and CXCL12 in central nervous system lymphoma patients. Clin Cancer Res. 2009;15(19):5968–73. doi: 10.1158/1078-0432.CCR-09-0108. DOI: https://doi.org/10.1158/1078-0432.CCR-09-0108
  66. Smith JR, Falkenhagen KM, Coupland SE, et al. Malignant B cells from patients with primary central nervous system lymphoma express stromal cell-derived factor-1. Am J Clin Pathol. 2007;127(4):633–41. doi: 10.1309/NUQHJ79BHWYD9TAF. DOI: https://doi.org/10.1309/NUQHJ79BHWYD9TAF
  67. Rubenstein JL, Wong VS, Kadoch C, et al. CXCL13 plus interleukin 10 is highly specific for the diagnosis of CNS lymphoma. Blood. 2013;121(23):4740–8. doi: 10.1182/blood-2013-01-476333. DOI: https://doi.org/10.1182/blood-2013-01-476333
  68. Bashir, R. Coakham H, Hochberg F. Expression of LFA-1/ICAM-1 in CNS lymphomas: possible mechanism for lymphoma homing into the brain. J Neurooncol. 1992;12(2):103–10. doi: 10.1007/BF00172658. DOI: https://doi.org/10.1007/BF00172658
  69. Moller P, Eichelmann A, Koretz K, Mechtersheimer G. Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia. Leukemia. 1992;6(4):256–64.
  70. Terol MJ, Lopez-Guillermo A, Bosch F, et al. Expression of beta-integrin adhesion molecules in non-Hodgkin’s lymphoma: correlation with clinical and evolutive features. J Clin Oncol. 1999;17(6):1869–75. doi: 10.1200/JCO.1999.17.6.1869. DOI: https://doi.org/10.1200/JCO.1999.17.6.1869
  71. Angelopoulou MK, Kontopidou GA, Pangalis FN. Adhesion molecules in B-chronic lymphoproliferative disorders. Semin Hematol. 1999;36(2):178–97.
  72. Rubenstein JL, Fridlyand J, Shen A, et al. Gene expression and angiotropism in primary CNS lymphoma. Blood. 2006;107(9):3716–23. doi: 10.1182/blood-2005-03-0897. DOI: https://doi.org/10.1182/blood-2005-03-0897
  73. Kim M, Kizilbash SH, Laramy JK, et al. Barriers to effective drug treatment for brain metastases: a multifactorial problem in the delivery of precision medicine. Pharm Res. 2018;35(9):177. doi: 10.1007/s11095-018-2455-9. DOI: https://doi.org/10.1007/s11095-018-2455-9
  74. Bechmann I, Galea I, Perry VH. What is the blood-brain barrier (not)? Trends Immunol. 2007;28(1):5–11. doi: 10.1016/j.it.2006.11.007. DOI: https://doi.org/10.1016/j.it.2006.11.007
  75. Pardridge WM. Delivery of biologics across the blood-brain barrier with molecular Trojan horse technology. BioDrugs. 2017;31(6):503–19. doi: 10.1007/s40259-017-0248-z. DOI: https://doi.org/10.1007/s40259-017-0248-z
  76. Gampa G, Vaidhyanathan S, Sarkaria JN, Elmquist WF. Drug delivery to melanoma brain metastases: can current challenges lead to new opportunities? Pharmacol Res. 2017;123:10–25. doi: 10.1016/j.phrs.2017.06.008. DOI: https://doi.org/10.1016/j.phrs.2017.06.008
  77. Medesan C, Radu C, Kim JK, et al. Localization of the site of the IgG molecule that regulates maternofetal transmission in mice. Eur J Immunol. 1996;26(10):2533–6. doi: 10.1002/eji.1830261038. DOI: https://doi.org/10.1002/eji.1830261038
  78. Wang W, Wang EQ, Balthasar JP. Monoclonal antibody pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther. 2008;84(5):548–58. doi: 10.1038/clpt.2008.170. DOI: https://doi.org/10.1038/clpt.2008.170
  79. Scott-Taylor TH, Axinia SC, Amin S, et al. Immunoglobulin G; structure and functional implications of different subclass modifications in initiation and resolution of allergy. Immunity Inflamm Dis. 2018;6(1):13–33. doi: 10.1002/iid3.192. DOI: https://doi.org/10.1002/iid3.192
  80. Pluim D, Ros W, Van Bussel MTJ, et al. Enzyme linked immunosorbent assay for the quantification of nivolumab and pembrolizumab in human serum and cerebrospinal fluid. J Pharm Biomed Anal. 2018;164:128–34. doi: 10.1016/j.jpba.2018.10.025. DOI: https://doi.org/10.1016/j.jpba.2018.10.025
  81. Muscal JA, Sun Y, Nuchtern JG, et al. Plasma and cerebrospinal fluid pharmacokinetics of thalidomide and lenalidomide in nonhuman primates. Cancer Chemother Pharmacol. 2012;69(4):943–7. doi: 10.1007/s00280-011-1781-y. DOI: https://doi.org/10.1007/s00280-011-1781-y
  82. Warren KE, Goldman S, Pollack IF, et al. Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors: Pediatric Brain Tumor Consortium study PBTC-018. J Clin Oncol. 2011;29(3):324–9. doi: 10.1200/JCO.2010.31.3601. DOI: https://doi.org/10.1200/JCO.2010.31.3601
  83. Rubenstein JL, Treseler PA, Stewart PJ. Regression of refractory intraocular large B-cell lymphoma with lenalidomide monotherapy. J Clin Oncol. 2011;29(20):595–7. doi: 10.1200/JCO.2011.34.7252. DOI: https://doi.org/10.1200/JCO.2011.34.7252
  84. Rubenstein JL, Rosenberg J, Damon L. High-dose methotrexate plus rituximab (Anti-CD20) monoclonal antibody in the treatment of primary CNS lymphoma. Society for Neuro-Oncology 4th annual meeting, Scottsdale, AZ; 1999. Abstract.
  85. Harjunpää A, Wiklund T, Collan J, et al. Complement activation in circulation and central nervous system after rituximab (anti-CD20) treatment of B-cell lymphoma. Leuk Lymphoma. 2001;42(4):731–8. doi: 10.3109/10428190109099335. DOI: https://doi.org/10.3109/10428190109099335
  86. Yip V, Lee MV, Saad OM, et al. Preclinical characterization of the distribution, catabolism, and elimination of a Polatuzumab Vedotin-Piiq (POLIVY®) antibody–drug conjugate in sprague dawley rats. J Clin Med. 2021;10(6):1323. doi: 10.3390/jcm10061323.
  87. Yu H, Kong H, Li C, et al. Bruton’s tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution. Transl Cancer Res. 2021;10(5):1975–83. doi: 10.21037/tcr-21-50. DOI: https://doi.org/10.21037/tcr-21-50
  88. Australia T.G.A. Australian Public Assessment Report for Acalabrutinib. Health Do. 2024. Available from: https://www.tga.gov.au/auspar/auspar-acalabrutinib (accessed 28.05.2024).
  89. Barrett A, Eyre TA, Bhuva S, et al. Complete response of mantle cell lymphoma with central nervous system involvement at diagnosis with acalabrutinib – Case report. EJHaem. 2023;5(1):238–41. doi: 10.1002/jha2.830. DOI: https://doi.org/10.1002/jha2.830
  90. Rios A, Rekoff G, Dinh B, et al. MCL-247: durable response of a patient with a mantle cell lymphoma central nervous system (CNS) relapse to treatment with a Bruton tyrosine kinase inhibitor (BTKi) monotherapy. Clin Lymphoma Myeloma Leuk. 2020;20(1):259–60. doi: 10.1016/S2152-2650(20)30862-4. DOI: https://doi.org/10.1016/S2152-2650(20)30862-4
  91. Yohannan B, Sridhar A, Nguyen N, et al. Durable remission with Bruton’s tyrosine kinase inhibitor therapy in a patient with leptomeningeal disease secondary to relapsed mantle cell lymphoma. BMJ Case Rep. 2022;15(6):e249631. doi: 10.1136/bcr-2022-249631. DOI: https://doi.org/10.1136/bcr-2022-249631
  92. Reda G, Cassin R, Dovrtelova G, et al. Venetoclax penetrates in cerebrospinal fluid and may be effective in chronic lymphocytic leukemia with central nervous system involvement. Haematologica. 2019;104(5):222–3. doi: 10.3324/haematol.2018.213157. DOI: https://doi.org/10.3324/haematol.2018.213157
  93. Ahmed G, Alsouqi A, Szabo A, et al. CAR T-cell therapy in mantle cell lymphoma with secondary CNS involvement: a multicenter experience. Blood Adv. 2024;8(13):3528–31. doi: 10.1182/bloodadvances.2023012255. DOI: https://doi.org/10.1182/bloodadvances.2023012255
  94. Zhang Y, Li Y, Zhuang Z, et al. Preliminary evaluation of zanubrutinib-containing regimens in DLBCL and the cerebrospinal fluid distribution of zanubrutinib: a 13-case series. Front Oncol. 2021;11:760405. doi: 10.3389/fonc.2021.760405. DOI: https://doi.org/10.3389/fonc.2021.760405
  95. FDA Approved Drug Products: JAYPIRCA (pirtobrutinib) tablets for oral use. Available from: https://pi.lilly.com/us/jaypirca-uspi.pdf?s=pi (accessed 30.09.2024).
  96. Zhang Y, Wang W, Zhao D, et al. 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. 2022;6(S3):256–7. DOI: https://doi.org/10.1097/01.HS9.0000843788.10370.07
  97. Liston DR, Davis M. Clinically relevant concentrations of anticancer drugs: a guide for nonclinical studies. Clin Cancer Res. 2017;23(14):3489–98. doi: 10.1158/1078-0432.CCR-16-3083. DOI: https://doi.org/10.1158/1078-0432.CCR-16-3083
  98. 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
  99. Kizhedath A, Wilkinson S, Glassey J. Applicability of traditional in vitro toxicity tests for assessing adverse effects of monoclonal antibodies: A case study of rituximab and trastuzumab. Antibodies. 2018;7(3):30. doi: 10.3390/antib7030030. DOI: https://doi.org/10.3390/antib7030030
  100. Zhai J, Qin Y, Zhu J, et al. Pharmacokinetics of obinutuzumab in Chinese patients with B-cell lymphomas. Br J Clin Pharmacol. 2017;83(7):1446–56. doi: 10.1111/bcp.13232. DOI: https://doi.org/10.1111/bcp.13232
  101. US Food and Drug Administration (FDA). FDA drug safety communication: FDA approval of Polivy (polatuzumab vedotin-piiq) for previously untreated diffuse large B-cell lymphoma, not otherwise specified, and high-grade B-cell lymphoma. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-polivy-polatuzumab-vedotin-piiq-previously-untreated-diffuse (accessed 30.09.2024).
  102. Yip V, Lee MV, Saad OM, et al. Preclinical characterization of the distribution, catabolism, and elimination of a polatuzumab vedotin-piiq (Polivy®) antibody–drug conjugate in sprague dawley rats. J Clin Med. 2021;10(6):1323. doi: 10.3390/jcm10061323. DOI: https://doi.org/10.3390/jcm10061323
  103. Shemesh CS, et al. Pharmacokinetics of polatuzumab vedotin in combination with R/G-CHP in patients with B-cell non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2020;85(5):831–42. doi: 10.1007/s00280-020-04054-8. DOI: https://doi.org/10.1007/s00280-020-04054-8
  104. Salem AH, Badawi MA, Place AE, et al. Venetoclax crosses the blood brain barrier: a pharmacokinetic analysis of the cerebrospinal fluid in pediatric leukemia patients. Blood. 2020;136(Suppl 1):30–1. doi: 10.1182/blood-2020-137197. DOI: https://doi.org/10.1182/blood-2020-137197
  105. Badawi M, Menon R, Place AE, et al. Venetoclax Penetrates the Blood Brain Barrier: A Pharmacokinetic Analysis in Pediatric Leukemia Patients. J Cancer. 2023;14(7):1151–6. doi: 10.7150/jca.81795. DOI: https://doi.org/10.7150/jca.81795
  106. Portnow J, Wang D, Blanchard MS, et al. Systemic Anti-PD-1 immunotherapy results in PD-1 blockade on T cells in the cerebrospinal fluid. JAMA Oncol. 2020;6(12):1947–51. doi: 10.1001/jamaoncol.2020.4508. DOI: https://doi.org/10.1001/jamaoncol.2020.4508
  107. Shirley M. Glofitamab: first approval. Drugs. 2023;83(10):935–91. doi: 10.1007/s40265-023-01894-5. DOI: https://doi.org/10.1007/s40265-023-01894-5
  108. 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
  109. Tecartus (brexucabtagene autoleucel) [package insert]. Santa Monica: Kite Pharma Inc; April 2024. Available from: https://www.gilead.com/-/media/files/pdfs/medicines/oncology/tecartus/tecartus-pi.pdf (accessed 30.09.2024).
  110. Siddiqi T, Wang X, Blanchard MS, et al. CD19-directed CAR T-cell therapy for treatment of primary CNS lymphoma. Blood Adv. 2021;5(20):4059–63. doi: 10.1182/bloodadvances.2020004106. DOI: https://doi.org/10.1182/bloodadvances.2020004106
  111. Ogasawara K, Lymp J, Mack T, et al. In vivo cellular expansion of lisocabtagene maraleucel and association with efficacy and safety in relapsed/refractory large B-cell lymphoma. Clin Pharmacol Ther. 2022;112(1):81–9. doi: 10.1002/cpt.2561. DOI: https://doi.org/10.1002/cpt.2561

Keywords:

mantle cell lymphoma, relapses involving CNS, ibrutinib, Bruton tyrosine kinase inhibitors, blood-brain barrier

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Author Biography

  • Evgenii Olegovich Kunevich, Leningrad Regional Clinical Hospital, 45 korp. 2A Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

    MD, PhD

2025-2

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Published

01.04.2025

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Vol. 18 No. 2 (2025)
CASE REPORTS

How to Cite

Kunevich E.O., Nemstsveridze N.N., Mikhaleva M.A., et al. Bruton Tyrosine Kinase Inhibitors for the Treatment of Relapsed Mantle Cell Lymphoma Involving CNS: Two Case Reports and Literature Review. Clinical Oncohematology. Basic Research and Clinical Practice. 2025;18(2):184–196. doi:10.21320/2500-2139-2025-18-2-184-196.

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