Г.С. Тумян
ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478
Для переписки: Гаяне Сепуговна Тумян, д-р мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; e-mail: gaytum@mail.ru
Для цитирования: Тумян Г.С. Мантийноклеточная лимфома: история, современные принципы диагностики, лечение (обзор литературы). Клиническая онкогематология. 2020;13(4):366–81.
DOI: 10.21320/2500-2139-2020-13-4-366-381
РЕФЕРАТ
Мантийноклеточная лимфома (МКЛ) — гетерогенное заболевание с широким спектром клинических проявлений от редких индолентных случаев, не требующих немедленного начала терапии, до агрессивных, быстро пролиферирующих типов опухоли. Разное клиническое поведение имеет молекулярное обоснование, которое позволило в последней редакции классификации опухолей кроветворной и лимфоидной тканей ВОЗ разделить МКЛ на два варианта: классический (в большинстве случаев) и индолентный. Последние десятилетия расширили наши представления о биологии и механизмах развития заболевания. Это делает возможным в дальнейшем стратифицировать больных на разные группы риска не только в зависимости от клинических факторов (MIPI), но и с учетом молекулярных и биологических особенностей опухоли (индекс пролиферации Ki-67, мутации генов ТР53, NOTCH1, NOTCH2, комплексный кариотип, немутантный статус IGHV). Алгоритмы лечения, основанные на интенсивной химиотерапии с включением цитарабина в высоких дозах, трансплантации аутологичных гемопоэтических стволовых клеток с дальнейшей поддерживающей терапией ритуксимабом, позволили длительно контролировать заболевание у значительного числа больных МКЛ. Применение новых «chemo-free» режимов и рациональных комбинаций (бортезомиб, ингибиторы BTK, леналидомид, венетоклакс) вселяет надежду на возможность ухода от традиционной химиотерапии у определенной части пациентов. Появление новых лекарственных средств с уникальными механизмами действия позволили в какой-то степени снять «печать фатальности» с МКЛ.
Ключевые слова: мантийноклеточная лимфома, лечение.
Получено: 17 июня 2020 г.
Принято в печать: 2 сентября 2020 г.
ЛИТЕРАТУРА
-
Rappaport H, Winter WJ, Hicks EB. Follicular lymphoma. A re-evaluation of its position in the scheme of malignant lymphoma, based on a survey of 253 cases. 1956;9(4):792–821. doi: 10.1002/1097-0142(195607/08)9:4<792::aid-cncr2820090429>3.0.co;2-b.
-
Gerard-Marchant R, Hamlin I, Lennert K, et al. Classification of non-Hodgkin’s lymphomas. Lancet. 1974;2:406–8.
-
Tubbs RR, Fishleder A, Weiss RA, et al. Immunohistologic cellular phenotypes of lymphoproliferative disorders. Comprehensive evaluation of 564 cases including 257 non-Hodgkin’s lymphomas classified by the International Working Formulation. Am J Pathol. 1983;113(2):207–21.
-
Banks PM, Chan J, Cleary ML, et al. Mantle cell lymphoma: a proposal for unification of morphologic, immunologic, and molecular data. Am J Surg Pathol. 1992;16(7):637–40. doi: 10.1097/00000478-199207000-00001.
-
Harris NL, Jaffe ES, Stein H, Banks PM. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361–92. doi: 10.1182/blood.v84.5.1361.bloodjournal8451361.
-
Dreyling M, Klapper W, Rule S. Blastoid and pleomorphic mantle cell lymphoma: still a diagnostic and therapeutic challenge! Blood. 2018;132(26):2722–9. doi: 10.1182/blood-2017-08-737502.
-
Hernandez L, Fest T, Cazorla M, et al. p53 gene mutations and protein overexpression are associated with aggressive variants of mantle cell lymphomas. Blood. 1996;87(8):3351–9. doi: 10.1182/blood.v87.8.3351.bloodjournal8783351.
-
Stefancikova L, Moulis M, Fabian P, et al. Loss of the p53 tumor suppressor activity is associated with negative prognosis of mantle cell lymphoma. Int J Oncol. 2010;36(3):699–706. doi: 10.3892/ijo_00000545.
-
Aukema SM, Hoster E, Rosenwald A, et al. Expression of TP53 is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network. Blood. 2018;131(4):417–20. doi: 10.1182/blood-2017-07-797019.
-
Hoster E, Rosenwald A, Berger F, et al. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results from Randomized Trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016;34(12):1386–94. doi: 10.1200/JCO.2015.63.8387.
-
Jiang W, Kahn SM, Zhou P, et al. Overexpression of Cyclin D1 in Rat Fibroblasts Causes Abnormalities in Growth Control, Cell Cycle Progression and Gene Expression. Oncogene. 1993;8(12):3447–57.
-
Jaffe ES, Harris NL, Stein H, Isaacson PG. Classification of lymphoid neoplasms: the microscope as a tool for disease discovery. Blood. 2008;112(12):4384–99. doi: 10.1182/blood-2008-07-077982.
-
Klener P. Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma. Int J Mol Sci. 2019;20(18):4417. doi: 10.3390/ijms20184417.
-
Jares P, Colomer D, Campo E. Genetic and molecular pathogenesis of mantle cell lymphoma: Perspectives for new targeted therapeutics. Nat Rev Cancer. 2007;7(10):750–62. doi: 10.1038/nrc2230.
-
Vincent-Fabert C, Fiancette R, Rouaud P, et al. A defect of the INK4-Cdk4 checkpoint and Myc collaborate in blastoid mantle cell lymphoma-like lymphoma formation in mice. Am J Pathol. 2012;180(4):1688–701. doi: 10.1016/j.ajpath.2012.01.004.
-
Choe JY, Yun JY, Na HY, et al. MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma. Histopathology. 2016;68(3):442–9. doi: 10.1111/his.12760.
-
Salaverria I, Royo C, Carvajal-Cuenca A, et al. CCND2 rearrangements are the most frequent genetic events in cyclin D1– mantle cell lymphoma. Blood. 2013;121(8):1394–402. doi: 10.1182/blood-2012-08-452284.
-
Bea S, Valdes-Mas R, Navarro A, et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci USA. 2013;110(45):18250–5. doi: 10.1073/pnas.1314608110.
-
Vegliante MC, Palomero J, Perez-Galan P, et al. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood. 2013;121(12):2175–85. doi: 10.1182/blood-2012-06-438937.
-
Kuo PY, Jatiani SS, Rahman AH, et al. SOX11 augments BCR signaling to drive MCL-like tumor development. Blood. 2018;131(20):2247–55. doi: 10.1182/blood-2018-02-832535.
-
Balsas P, Palomero J, Eguileor A, et al. SOX11 promotes tumor protective microenvironment interactions through CXCR4 and FAK regulation in mantle cell lymphoma. Blood. 2017;130(4):501–13. doi: 10.1182/blood-2017-04-776740.
-
Narurkar R, Alkayem M, Liu D. SOX11 is a biomarker for cyclin D1-negative mantle cell lymphoma. Biomark Res. 2016;4(1):6. doi: 10.1186/s40364-016-0060-9.
-
Zhang J, Jima D, Moffitt AB, et al. The genomic landscape of mantle cell lymphoma is related to the epigenetically determined chromatin state of normal B cells. Blood. 2014;123(19):2988–96. doi: 10.1182/blood-2013-07-517177.
-
Yang P, Zhang W, Wang J, et al. Genomic landscape and prognostic analysis of mantle cell lymphoma. Cancer Gene Ther. 2018;25(5–6):129–40. doi: 10.1038/s41417-018-0022-5.
-
Eskelund CW, Dahl C, Hansen JW, et al. TP53 Mutations Identify Younger Mantle Cell Lymphoma Patients Who Do Not Benefit From Intensive Chemoimmunotherapy. Blood. 2017;130(17):1903–10. doi: 10.1182/blood-2017-04-779736.
-
Morello L, Rattotti S, Giordano L, et al. Mantle Cell Lymphoma of Mucosa-Associated Lymphoid Tissue. A European Mantle Cell Lymphoma Network Study. Hemasphere. 2019;4(1):e302. doi: 10.1097/hs9.0000000000000302.
-
Hoster E, Dreyling M, Klapper W, et al. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008;111(2):558–65. doi: 10.1182/blood-2007-06-095331.
-
Scott DW, Abrisqueta P, Wright GW, et al. New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies. J Clin Oncol. 2017;35(15):1668–77. doi: 10.1200/jco.2016.70.7901.
-
Kridel R, Meissner B, Rogic S, et al. Whole transcriptome sequencing reveals recurrent NOTCH1 mutations in mantle cell lymphoma. Blood. 2012;119(9):1963–71. doi: 10.1182/blood-2011-11-391474.
-
Halldorsdottir AM, Lundin A, Murray F, et al. Impact of TP53 mutation and 17p deletion in mantle cell lymphoma. Leukemia. 2011;25(12):1904–8. doi: 10.1038/leu.2011.162.
-
Delfau-Larue MH, Klapper W, Berger F, et al. European Mantle Cell Lymphoma Network. High-dose cytarabine does not overcome the adverse prognostic value of CDKN2A and TP53 deletions in mantle cell lymphoma. Blood. 2015;126(5):604–11. doi: 10.1182/blood-2015-02-628792.
-
Cohen JB. TP53 mutations in MCL: more therapy is not better. Blood. 2017;130(17):1876–7. doi: 10.1182/blood-2017-08-803551.
-
Jain P, Wang M. Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management. Am J Hematol. 2019;94(6):710–25. doi: 10.1002/ajh.25487.
-
Chihara D, Cheah CY, Westin JR, et al. Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center. Br J Haematol. 2016;172(1):80–8. doi: 10.1111/bjh.13796.
-
Romaguera JE, Wang M, Feng L, et al. Phase 2 trial of bortezomib in combination with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with bortezomib, rituximab, methotrexate, and cytarabine for untreated mantle cell lymphoma. Cancer. 2018;124(12):2561–9. doi: 10.1002/cncr.31361.
-
Merli F, Luminari S, Ilariucci F, et al. Rituximab plus HyperCVAD alternating with high dose cytarabine and methotrexate for the initial treatment of patients with mantle cell lymphoma, a multicentre trial from Gruppo Italiano studio Linfomi. Br J Haematol. 2012;156(3):346–53. doi: 10.1111/j.1365-2141.2011.08958.x.
-
Bernstein SH, Epner E, Unger JM, et al. A phase II multicenter trial of hyperCVAD MTX/Ara-C and rituximab in patients with previously untreated mantle cell lymphoma; SWOG 0213. Ann Oncol. 2013;24(6):1587–93. doi: 10.1093/annonc/mdt070.
-
Eskelund CW, Kolstad A, Jerkeman M, et al. 15-year follow-up of the second Nordic mantle cell lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016;175(3):410–8. doi: 10.1111/bjh.14241.
-
Hermine O, Hoster E, Walewski J, et al. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL younger): a randomised, open-label, phase 3 trial of the European mantle cell lymphoma network. Lancet. 2016;388(10044):565–75. doi: 10.1016/S0140-6736(16)00739-X.
-
Armand P, Redd R, Bsat J, et al. A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for transplant-eligible patients with mantle cell lymphoma. Br J Haematol. 2016;173(1):89–95. doi: 10.1111/bjh.13929.
-
Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377(13):1250–60. doi: 10.1056/NEJMoa1701769.
-
Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020;38(3):248–56. doi: 10.1200/JCO.19.01294.
-
Rummel MJ, Niederle N, Maschmeyer G, et al. Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013;381(9873):1203–10. doi: 10.1016/S0140-6736(12)61763-2.
-
Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or RCHOP/RVP in first line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014;123(19):2944–52. doi: 10.1182/blood-2013-11-531327.
-
Kluin-Nelemans JC, Hoster E, Hermine O, et al. Treatment of older patients with mantle cell lymphoma. N Engl J Med. 2012;367(6):520–31. doi: 10.1056/NEJMoa1200920.
-
Robak T, Huang H, Jin J, et al. Bortezomib-based therapy for newly diagnosed mantle-cell lymphoma. N Engl J Med. 2015;372(10):944–53. doi: 10.1056/NEJMoa1412096.
-
Robak T, Jin J, Pylypenko H, et al. Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study. Lancet Oncol. 2018;19(11):1449–58. doi: 10.1016/S1470-2045(18)30685-5.
-
Ratnasingam S, Casan J, Shortt J, et al. Cytarabine-based induction immunochemotherapy in the front-line treatment of older patients with mantle cell lymphoma. Sci Rep. 2019;9(1):13544. doi: 10.1038/s41598-019-49776-9.
-
Visco C, Finotto S, Zambello R, et al. Combination of Rituximab, Bendamustine, and Cytarabine for Patients With Mantle-Cell Non-Hodgkin Lymphoma Ineligible for Intensive Regimens or Autologous Transplantation. J Clin Oncol. 2013;31(11):1442–9. doi: 10.1200/JCO.2012.45.9842.
-
Visco C, Chiappella A, Nassi L, et al. Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi. Lancet Haematol. 2017;4(1):e15–e23. doi: 10.1016/S2352-3026(16)30185-5.
-
Ruan J, Martin P, Christos P, et al. Five-year follow-up of lenalidomide plus rituximab as initial treatment of mantle cell lymphoma. Blood. 2018;132(19):2016–25. doi: 10.1182/blood-2018-07-859769.
-
Hoster E, Pott C. Minimal residual disease in mantle cell lymphoma: insights into biology and impact on treatment. Hematology. 2016;2016(1):437–45. doi: 10.1182/asheducation-2016.1.437.
-
Pott C, Bruggemann M, Ritgen M, et al. MRD detection in B-cell non-Hodgkin lymphomas using Ig gene rearrangements and chromosomal translocations as targets for real-time quantitative PCR. In: R Kuppers (ed). Lymphoma. Methods in Molecular Biology (Methods and Protocols). Vol. 971. Totowa: Humana Press; 2013. рр. 175–200. doi: 10.1007/978-1-62703-269-8_10.
-
Kumar A, Sha F, Toure A, et al. Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: Progressive shortening in response duration and survival after each relapse. Blood Cancer J. 2019;9(6):50. doi: 10.1038/s41408-019-0209-5.
-
Herrmann A, Hoster E, Zwingers T, et al. Improvement of overall survival in advanced stage mantle cell lymphoma. J Clin Oncol. 2009;27(4):511–8. doi: 10.1200/JCO.2008.16.8435.
-
Fisher RI, Bernstein SH, Kahl BS, et al. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006;24(30):4867–74. doi: 10.1200/JCO.2006.07.9665.
-
Chen RW, Palmer JM, Tomassetti S, et al. Multi-center phase II trial of bortezomib and rituximab maintenance combination therapy in patients with mantle cell lymphoma after consolidative autologous stem cell transplantation. J Hematol Oncol. 2018;11(1):87. doi: 10.1186/s13045-018-0631-3.
-
Albertsson-Lindblad A, Kolstad A, Laurell A, et al. Lenalidomide-bendamustine-rituximab in patients older than 65 years with untreated mantle cell lymphoma. Blood. 2016;128(14):1814–20. doi: 10.1182/blood-2016-03-704023.
-
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.
-
Rule S, Jurczak W, Jerkeman M, et al. Ibrutinib vs 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.
-
Rule S, Dreyling M, Goy A, et al. Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow-up from a pooled analysis. Haematologica. 2019;194(5):е211–е214. doi: 10.3324/haematol.2018.205229.
-
Wang M, Rule S, Zinzani PL, et al. Long-Term Follow-Up of Acalabrutinib Monotherapy in Patients with Relapsed/Refractory Mantle Cell Lymphoma. Clin Lymphoma Myel Leuk. 2019;19:S316. doi: 10.1016/j.clml.2019.07.291.
-
Telford C, Kabadi SM, Abhyankar S, et al. Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. Clin Ther. 2019;41(11):2357–79.e1. doi: 10.1016/j.clinthera.2019.09.012.
-
Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of Venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35(8):826–33. doi: 10.1200/JCO.2016.70.4320.
-
Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus Venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378(13):1211–23. doi: 10.1056/NEJMoa1715519.
-
Hess G, Herbrecht R, Romaguera J, et al. Phase III study to evaluate temsirolimus compared with investigator’s choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009;27(23):3822–9. doi: 10.1200/JCO.2008.20.7977.
-
Kahl BS, Spurgeon SE, Furman RR, et al. A phase 1 study of the PI3Kδ inhibitor idelalisib in patients with relapsed/refractory mantle cell lymphoma (MCL). Blood. 2014;123(22):3398–405. doi: 10.1182/blood-2013-11-537555.