Leveraging the Immunomodulatory Potential of Ibrutinib for Improved Outcomes of T Cell-Mediated Therapies of B Cell Malignancies: A Narrative Review

Susanibar-Adaniya S, Barta SK. 2021 update on diffuse large B cell lymphoma: a review of current data and potential applications on risk stratification and management. Am J Hematol. 2021;96(5):617–29.

Article  PubMed  PubMed Central  Google Scholar 

Freedman A, Jacobsen E. Follicular lymphoma: 2020 update on diagnosis and management. Am J Hematol. 2020;95(3):316–27.

Article  CAS  PubMed  Google Scholar 

Jain P, Wang ML. Mantle cell lymphoma in 2022—a comprehensive update on molecular pathogenesis, risk stratification, clinical approach, and current and novel treatments. Am J Hematol. 2022;97(5):638–56.

Article  CAS  PubMed  Google Scholar 

Shadman M. Diagnosis and treatment of chronic lymphocytic leukemia: a review. JAMA. 2023;329(11):918–32.

Article  CAS  PubMed  Google Scholar 

Woyach JA. Management of relapsed/refractory chronic lymphocytic leukemia. Am J Hematol. 2022;97(Suppl 2):S11–8.

PubMed  PubMed Central  Google Scholar 

Condoluci A, Rossi D. Biology and treatment of Richter transformation. Front Oncol. 2022;12: 829983.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Falchi L, Vardhana SA, Salles GA. Bispecific antibodies for the treatment of B-cell lymphoma: promises, unknowns, and opportunities. Blood. 2023;141(5):467–80.

Article  CAS  PubMed  Google Scholar 

Abbasi S, Totmaj MA, Abbasi M, et al. Chimeric antigen receptor T (CAR-T) cells: novel cell therapy for hematological malignancies. Cancer Med. 2023;12(7):7844–58.

Article  CAS  PubMed  Google Scholar 

IMBRUVICA (ibrutinib) [prescribing information]. South San Francisco: Pharmacyclics LLC; 2024.

Gill S, Vides V, Frey NV, et al. Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia. Blood Adv. 2022;6(21):5774–85.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qin JS, Johnstone TG, Baturevych A, et al. Antitumor potency of an anti-CD19 chimeric antigen receptor t-cell therapy, lisocabtagene maraleucel in combination with ibrutinib or acalabrutinib. J Immunother. 2020;43(4):107–20.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mhibik M, Gaglione EM, Eik D, et al. Cytotoxicity of the CD3×CD20 bispecific antibody epcoritamab in CLL is increased by concurrent BTK or BCL-2 targeting. Blood Adv. 2023;7(15):4089–101.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mhibik M, Gaglione EM, Eik D, et al. BTK inhibitors, irrespective of ITK inhibition, increase efficacy of a CD19/CD3-bispecific antibody in CLL. Blood. 2021;138(19):1843–54.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Luo W, Li C, Wu J, et al. Bruton tyrosine kinase inhibitors preserve anti-CD19 chimeric antigen receptor T-cell functionality and reprogram tumor micro-environment in B-cell lymphoma. Cytotherapy. 2023;25(7):739–49.

Article  CAS  PubMed  Google Scholar 

Kipps TJ, Stevenson FK, Wu CJ, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:16096.

Article  PubMed  PubMed Central  Google Scholar 

Man S, Henley P. Chronic lymphocytic leukaemia: the role of T cells in a B cell disease. Br J Haematol. 2019;186(2):220–33.

Article  PubMed  Google Scholar 

Riches JC, Davies JK, McClanahan F, et al. T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production. Blood. 2013;121(9):1612–21.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Palma M, Gentilcore G, Heimersson K, et al. T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers. Haematologica. 2017;102(3):562–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nunes C, Wong R, Mason M, Fegan C, Man S, Pepper C. Expansion of a CD8(+)PD-1(+) replicative senescence phenotype in early stage CLL patients is associated with inverted CD4:CD8 ratios and disease progression. Clin Cancer Res. 2012;18(3):678–87.

Article  CAS  PubMed  Google Scholar 

Brusa D, Serra S, Coscia M, et al. The PD-1/PD-L1 axis contributes to T-cell dysfunction in chronic lymphocytic leukemia. Haematologica. 2013;98(6):953–63.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wierz M, Janji B, Berchem G, Moussay E, Paggetti J. High-dimensional mass cytometry analysis revealed microenvironment complexity in chronic lymphocytic leukemia. Oncoimmunology. 2018;7(8): e1465167.

Article  PubMed  PubMed Central  Google Scholar 

Görgün G, Holderried TA, Zahrieh D, Neuberg D, Gribben JG. Chronic lymphocytic leukemia cells induce changes in gene expression of CD4 and CD8 T cells. J Clin Invest. 2005;115(7):1797–805.

Article  PubMed  PubMed Central  Google Scholar 

Kabanova A, Sanseviero F, Candi V, et al. Human cytotoxic T lymphocytes form dysfunctional immune synapses with B cells characterized by non-polarized lytic granule release. Cell Rep. 2016;15(1):9–18.

Article  CAS  PubMed  Google Scholar 

Roessner PM, Seiffert M. T cells in chronic lymphocytic leukemia: guardians or drivers of disease? Leukemia. 2020;34(8):2012–24.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ramsay AG, Johnson AJ, Lee AM, et al. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest. 2008;118(7):2427–37.

CAS  PubMed  PubMed Central  Google Scholar 

Purroy N, Tong YE, Lemvigh CK, et al. Single-cell analysis reveals immune dysfunction from the earliest stages of CLL that can be reversed by ibrutinib. Blood. 2022;139(14):2252–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wu J, Xu X, Lee EJ, et al. Phenotypic alteration of CD8+ T cells in chronic lymphocytic leukemia is associated with epigenetic reprogramming. Oncotarget. 2016;7(26):40558–70.

Article  PubMed  PubMed Central  Google Scholar 

Giannopoulos K, Schmitt M, Kowal M, et al. Characterization of regulatory T cells in patients with B-cell chronic lymphocytic leukemia. Oncol Rep. 2008;20(3):677–82.

PubMed  Google Scholar 

Beyer M, Kochanek M, Darabi K, et al. Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine. Blood. 2005;106(6):2018–25.

Article  CAS  PubMed  Google Scholar 

D’Arena G, Laurenti L, Minervini MM, et al. Regulatory T-cell number is increased in chronic lymphocytic leukemia patients and correlates with progressive disease. Leuk Res. 2011;35(3):363–8.

Article  PubMed  Google Scholar 

Piper KP, Karanth M, McLarnon A, et al. Chronic lymphocytic leukaemia cells drive the global CD4+ T cell repertoire towards a regulatory phenotype and leads to the accumulation of CD4+ forkhead box P3+ T cells. Clin Exp Immunol. 2011;166(2):154–63.

Article  CAS  PubMed  PubMed Central 

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