Bruton Tyrosine Kinase Inhibitors for the Treatment of Mantle Cell Lymphoma: A Literature Review and Our Own Experience

AIM. To assess the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKi) as first and subsequent lines of mantle cell lymphoma (MCL) therapy.

MATERIALS & METHODS. This study enrolled 30 patients with newly diagnosed (ndMCL; n = 17) and relapsed/refractory MCL (r/r MCL; n = 13) treated with BTKi at the Drug Chemotherapy and Hematology Department of the NN Blokhin National Medical Cancer Research Center during 2016–2025. NdMCL patients less than 60 years of age (n = 10/17; 58 %) were treated with alternating regimen R-CHOP + I/R-DHAOx combined with BTKi, 6 of them received high-dose chemotherapy with autologous hematopoietic stem cell transplantation. Elderly ndMCL patients (n = 7/17; 41 %) were treated with R-B program combined with BTKi. Irrespective of the induction phase, rituximab maintenance therapy (3 years) and BTKi (2 years) were administered to all patients. For the treatment of r/r MCL, BTKi was used as a monoregimen in 6 (46 %) patients, 2 (15 %) patients received it in combination with R-B, and 5 (38 %) in combination with rituximab.

RESULTS. With the median follow-up of 36 months, ndMCL patients (n = 17) showed the 3-year progression-free survival (PFS) of 81.4 % and the 3-year overall survival (OS) of 84.4 %. In the r/r MCL group, with the median follow-up of 22 months, the 3-year PFS was 60.9 %, and the 3-year OS was 67 %. During this time, in the period from 3 to 23 months, 3 patients died (2 of them due to disease progression and 1 died from an infection). Toxicity profile of BTKi combination appeared to be manageable, whereas more infectious complications (53.8 % vs. 35.3 %) and more cases of pneumonia (53.8 vs. 29.4 %) were observed in r/r MCL vs. ndMCL patients.

CONCLUSION. The administration of BTKi combined with chemotherapy is associated with high efficacy and favorable toxicity profile in the treatment of both ndMCL and r/r MCL.

• Ulyana Gordeevna Koshkina NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0009-0000-1023-5426 (unauthenticated)
• A.A. Semenova NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0000-0003-4951-3053 (unauthenticated)
• M.Yu. Kichigina NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0000-0002-2715-2528 (unauthenticated)
• D.N. Tupitsyna NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0009-0003-4830-1160 (unauthenticated)
• V.O. Shpirko NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0000-0002-2300-0332 (unauthenticated)
• A.I. Cherencova NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0009-0002-3791-0107 (unauthenticated)
• S.F. Ramazanova NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0009-0008-7084-0060 (unauthenticated)
• N.O. Zemlyakov NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0009-0006-0441-3533 (unauthenticated)
• I.Z. Zavodnova NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0000-0001-6674-8634 (unauthenticated)
• A.V. Arakelyan NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522; IM Sechenov First Moscow State Medical University, 2 korp. 4 Bolshaya Pirogovskaya ul., Moscow, Russian Federation, 119435 https://orcid.org/0000-0003-4911-0959 (unauthenticated)
• G.D. Petrova NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0000-0003-4207-2822 (unauthenticated)
• O.Yu. Baranova NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522 https://orcid.org/0000-0002-0202-8176 (unauthenticated)
• G.S. Tumyan NN Blokhin National Medical Cancer Research Center, 23 Kashirskoye sh., Moscow, Russian Federation, 115522; Russian Medical Academy of Postgraduate Education, 2/1 Barrikadnaya ul., Moscow, Russian Federation, 125993 https://orcid.org/0000-0002-5771-4413 (unauthenticated)

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