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Review

Immunological changes with kinase inhibitor therapy for chronic lymphocytic leukemia

ORCID Icon, & ORCID Icon
Pages 2792-2800 | Received 10 Jan 2018, Accepted 13 Mar 2018, Published online: 15 May 2018

References

  • Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376:1164–1174.
  • Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17:928–942.
  • Keating MJ, O'Brien S, Albitar M, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol. 2005;23:4079–4088.
  • Badoux XC, Keating MJ, Wang X, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood. 2011;117:3016–3024.
  • Robak T, Dmoszynska A, Solal CP, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol. 2010;28:1756–1765.
  • Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32–42.
  • Sun C, Tian X, Lee YS, et al. Partial reconstitution of humoral immunity and fewer infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Blood. 2015;126:2213–2219.
  • Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373:2425–2437.
  • Farooqui MZ, Valdez J, Martyr S, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16:169–176.
  • Jou ST, Carpino N, Takahashi Y, et al. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol. 2002;22:8580–8591.
  • Coutre SE, Furman RR, Sharman JP. Second interim analysis of a phase 3 study evaluating idelalisib and rituximab for relapsed CLL. J Clin Oncol. 2014;32:5s. (abstract 7012).
  • Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370:997–1007.
  • O'Brien SM, Lamanna N, Kipps TJ, et al. A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia. Blood. 2015;126:2686–2694.
  • U.S. Food & Drug Administration. FDA alerts healthcare professionals about clinical trials with zydelig (idelalisib) in combination with other cancer medicines 2016 [updated 2016 Mar 14; cited 2017 Apr 12]. Available from: https://www.fda.gov/Drugs/DrugSafety/ucm490618.htm
  • Cheah CY, Fowler NH. Idelalisib in the management of lymphoma. Blood. 2016;128:331–336.
  • Zelenetz AD, Barrientos JC, Brown JR, et al. Idelalisib or placebo in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukaemia: interim results from a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2017;18:297–311.
  • Sehn LH, Hallek M, Jurczak W. Paper presented at: A retrospective analysis of pneumocystis Jirovecii pneumonia infection in patients receiving idelalisib in clinical trials. American Society of Hematology. 58th Annual Meeting; 2016 Dec 3–5: abstr 3705; San Diego, CA.
  • Ahn IE, Jerussi T, Farooqui M, et al. Atypical Pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016;128:1940–1943.
  • Ruchlemer R, Ben Ami R, Lachish T. Ibrutinib for chronic lymphocytic leukemia. N Engl J Med. 2016;374:1593–1594.
  • Lionakis MS, Dunleavy K, Roschewski M, et al. Inhibition of B cell receptor signaling by ibrutinib in primary CNS lymphoma. Cancer Cell. 2017;31:833–843.e5.
  • Giridhar KV, Shanafelt T, Tosh PK, et al. Disseminated herpes zoster in chronic lymphocytic leukemia (CLL) patients treated with B-cell receptor pathway inhibitors. Leuk Lymphoma. 2017;58:1973–1976.
  • de Jesus Ngoma P, Kabamba B, Dahlqvist G, et al. Occult HBV reactivation induced by ibrutinib treatment: a case report. Acta Gastroenterol Belg. 2015;78:424–426.
  • Chan KL, Lokan J, Tam CS, et al. Central nervous system immune reconstitution inflammatory syndrome after ibrutinib therapy for Richter transformation. Leuk Lymphoma. 2017;58:207–210.
  • Dearden C, Wade R, Else M, et al. The prognostic significance of a positive direct antiglobulin test in chronic lymphocytic leukemia: a beneficial effect of the combination of fludarabine and cyclophosphamide on the incidence of hemolytic anemia. Blood. 2008;111:1820–1826.
  • Zent CS, Ding W, Reinalda MS, et al. Autoimmune cytopenia in chronic lymphocytic leukemia/small lymphocytic lymphoma: changes in clinical presentation and prognosis. Leuk Lymphoma. 2009;50:1261–1268.
  • Maura F, Visco C, Falisi E, et al. B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia. Am J Hematol. 2013;88:32–36.
  • Weiss RB, Freiman J, Kweder SL, et al. Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia. J Clin Oncol. 1998;16:1885–1889.
  • Vitale C, Ahn IE, Sivina M, et al. Autoimmune cytopenias in patients with chronic lymphocytic leukemia treated with ibrutinib. Haematologica. 2016;101:e254–e258.
  • Molica S, Levato L, Mirabelli R. Chronic lymphocytic leukemia, autoimmune hemolytic anemia and ibrutinib: a case report and review of the literature. Leuk Lymphoma. 2016;57:735–737.
  • Lampson BL, Kasar SN, Matos TR, et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood. 2016;128:195–203.
  • Burris HA III, Flinn IW, Patel MR, et al. Umbralisib, a novel PI3Kdelta and casein kinase-1epsilon inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol. 2018;19:486–496.
  • Herman SE, Mustafa RZ, Gyamfi JA, et al. Ibrutinib inhibits BCR and NF-kappaB signaling and reduces tumor proliferation in tissue-resident cells of patients with CLL. Blood. 2014;123:3286–3295.
  • Hoellenriegel J, Meadows SA, Sivina M, et al. The phosphoinositide 3'-kinase delta inhibitor, CAL-101, inhibits B-cell receptor signaling and chemokine networks in chronic lymphocytic leukemia. Blood. 2011;118:3603–3612.
  • Herman SE, Mustafa RZ, Jones J, et al. Treatment with Ibrutinib Inhibits BTK- and VLA-4-dependent adhesion of chronic lymphocytic leukemia cells in vivo. Clin Cancer Res. 2015;21:4642–4651.
  • de Rooij MF, Kuil A, Geest CR, et al. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood. 2012;119:2590–2594.
  • Herman SE, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117:6287–6296.
  • Cheng S, Ma J, Guo A, et al. BTK inhibition targets in vivo CLL proliferation through its effects on B-cell receptor signaling activity. Leukemia. 2014;28:649–657.
  • Sun C, Wiestner A. Prognosis and therapy of chronic lymphocytic leukemia and small lymphocytic lymphoma. Cancer Treat Res. 2015;165:147–175.
  • Sun C, Gao J, Couzens L, et al. Seasonal influenza vaccination in patients with chronic lymphocytic leukemia treated with ibrutinib. JAMA Oncol. 2016;2:1656–1657.
  • Schliffke S, Sivina M, Kim E, et al. Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy. Oncoimmunology. 2018;0:e1417720.
  • Brown JR, Byrd JC, Coutre SE, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110delta, for relapsed/refractory chronic lymphocytic leukemia. Blood. 2014;123:3390–3397.
  • Herman SE, Gordon AL, Wagner AJ, et al. Phosphatidylinositol 3-kinase-delta inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals. Blood. 2010;116:2078–2088.
  • Ringshausen I, Schneller F, Bogner C, et al. Constitutively activated phosphatidylinositol-3 kinase (PI-3K) is involved in the defect of apoptosis in B-CLL: association with protein kinase Cdelta. Blood. 2002;100:3741–3748.
  • Compagno M, Wang Q, Pighi C, et al. Phosphatidylinositol 3-kinase delta blockade increases genomic instability in B cells. Nature. 2017;542:489–493.
  • Niemann CU, Herman SE, Maric I, et al. Disruption of in vivo chronic lymphocytic leukemia tumor-microenvironment interactions by ibrutinib - findings from an investigator-initiated phase II study. Clin Cancer Res. 2016;22:1572–1582.
  • 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;121:1612–1621.
  • 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;118:2427–2437.
  • Dubovsky JA, Beckwith KA, Natarajan G, et al. Ibrutinib is an irreversible molecular inhibitor of ITK driving a Th1-selective pressure in T lymphocytes. Blood. 2013;122:2539–2549.
  • Berg LJ, Finkelstein LD, Lucas JA, et al. Tec family kinases in T lymphocyte development and function. Annu Rev Immunol. 2005;23:549–600.
  • Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2014;15:1090–1099.
  • Yin Q, Sivina M, Robins H, et al. Ibrutinib therapy increases T cell repertoire diversity in patients with chronic lymphocytic leukemia. J Immunol. 2017;198:1740–1747.
  • Kashiwakura J, Suzuki N, Nagafuchi H, et al. Txk, a nonreceptor tyrosine kinase of the Tec family, is expressed in T helper type 1 cells and regulates interferon gamma production in human T lymphocytes. J Exp Med. 1999;190:1147–1154.
  • Ruella M, Kenderian SS, Shestova O, et al. Kinase inhibitor ibrutinib to prevent cytokine-release syndrome after anti-CD19 chimeric antigen receptor T cells for B-cell neoplasms. Leukemia. 2017;31:246–248.
  • Long M, Beckwith K, Do P, et al. Ibrutinib treatment improves T cell number and function in CLL patients. J Clin Invest. 2017;127:3052–3064.
  • Gomez-Rodriguez J, Wohlfert EA, Handon R, et al. Itk-mediated integration of T cell receptor and cytokine signaling regulates the balance between Th17 and regulatory T cells. J Exp Med. 2014;211:529–543.
  • Fraietta JA, Beckwith KA, Patel PR, et al. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia. Blood. 2016;127:1117–1127.
  • Sagiv-Barfi I, Kohrt HE, Czerwinski DK, et al. Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK. Proc Natl Acad Sci USA. 2015;112:E966–E972.
  • Ding W, LaPlant BR, Call TG, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017;129:3419–3427.
  • Robinson HR, Qi J, Baskar S, et al. Paper presented at: Activity of CD19/CD3 bispecific antibodies in chronic lymphocytic leukemia. American Society of Hematology. 59th Annual Meeting; 2017 Dec 1–4; Atlanta, GA.
  • Ali K, Soond DR, Pineiro R, et al. Inactivation of PI(3)K p110delta breaks regulatory T-cell-mediated immune tolerance to cancer. Nature. 2014;510:407–411.
  • Okkenhaug K, Bilancio A, Farjot G, et al. Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science. 2002;297:1031–1034.
  • Uno JK, Rao KN, Matsuoka K, et al. Altered macrophage function contributes to colitis in mice defective in the phosphoinositide-3 kinase subunit p110delta. Gastroenterology. 2010;139:1642–1653.
  • Weidner AS, Panarelli NC, Geyer JT, et al. Idelalisib-associated colitis: histologic findings in 14 patients. Am J Surg Pathol. 2015;39:1661–1667.
  • Hanna BS, McClanahan F, Yazdanparast H, et al. Depletion of CLL-associated patrolling monocytes and macrophages controls disease development and repairs immune dysfunction in vivo. Leukemia. 2016;30:570–579.
  • Nguyen PH, Fedorchenko O, Rosen N, et al. LYN kinase in the tumor microenvironment is essential for the progression of chronic lymphocytic leukemia. Cancer Cell. 2016;30:610–622.
  • Herman SE, Wiestner A. Preclinical modeling of novel therapeutics in chronic lymphocytic leukemia: the tools of the trade. Semin Oncol. 2016;43:222–232.
  • Burger JA, Tsukada N, Burger M, et al. Blood-derived nurse-like cells protect chronic lymphocytic leukemia B cells from spontaneous apoptosis through stromal cell-derived factor-1. Blood. 2000;96:2655–2663.
  • Nagaraj S, Youn JI, Gabrilovich DI. Reciprocal relationship between myeloid-derived suppressor cells and T cells. J Immunol. 2013;191:17–23.
  • Jitschin R, Braun M, Buttner M, et al. CLL-cells induce IDOhi CD14 + HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs. Blood. 2014;124:750–760.
  • Gustafson MP, Abraham RS, Lin Y, et al. Association of an increased frequency of CD14+ HLA-DR lo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL). Br J Haematol. 2012;156:674–676.
  • Giannoni P, Pietra G, Travaini G, et al. Chronic lymphocytic leukemia nurse-like cells express hepatocyte growth factor receptor (c-MET) and indoleamine 2,3-dioxygenase and display features of immunosuppressive type 2 skewed macrophages. Haematologica. 2014;99:1078–1087.
  • Fiedler K, Sindrilaru A, Terszowski G, et al. Neutrophil development and function critically depend on Bruton tyrosine kinase in a mouse model of X-linked agammaglobulinemia. Blood. 2011;117:1329–1339.
  • Mueller H, Stadtmann A, Van Aken H, et al. Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways. Blood. 2010;115:3118–3127.
  • Honda F, Kano H, Kanegane H, et al. The kinase Btk negatively regulates the production of reactive oxygen species and stimulation-induced apoptosis in human neutrophils. Nat Immunol. 2012;13:369–378.
  • Kok K, Nock GE, Verrall EA, et al. Regulation of p110delta PI 3-kinase gene expression. PLoS One. 2009;4:e5145.
  • Ponader S, Chen SS, Buggy JJ, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119:1182–1189.
  • Ping L, Ding N, Shi Y, et al. The Bruton's tyrosine kinase inhibitor ibrutinib exerts immunomodulatory effects through regulation of tumor-infiltrating macrophages. Oncotarget. 2017;8:39218–39229.
  • Da Roit F, Engelberts PJ, Taylor RP, et al. Ibrutinib interferes with the cell-mediated anti-tumor activities of therapeutic CD20 antibodies: implications for combination therapy. Haematologica. 2015;100:77–86.
  • Skarzynski M, Niemann CU, Lee YS, et al. Interactions between Ibrutinib and anti-CD20 antibodies: competing effects on the outcome of combination therapy. Clin Cancer Res. 2016;22:86–95.
  • Kohrt HE, Sagiv-Barfi I, Rafiq S, et al. Ibrutinib (PCI-32765) antagonizes rituximab-dependent NK-cell mediated cytotoxicity. Blood. 2013;122:373.
  • Ren L, Campbell A, Fang H, et al. Analysis of the effects of the Bruton's tyrosine kinase (Btk) inhibitor ibrutinib on monocyte fcgamma receptor (FcgammaR) function. J Biol Chem. 2016;291:3043–3052.
  • Gunderson AJKM, Coussens LM, et al. Bruton tyrosine kinase-dependent immune cell cross-talk drives pancreas cancer. Cancer Discov. 2016;6:270–285.
  • Stiff A, Trikha P, Wesolowski R, et al. Myeloid-derived suppressor cells express Bruton's tyrosine kinase and can be depleted in tumor-bearing hosts by Ibrutinib treatment. Cancer Res. 2016;76:2125–2136.
  • McClanahan F, Reiff SD, Guinn D. Paper presented at: Exploring the functional relevance of BTK beyond chronic lymphocytic leukemia (CLL) cells: BTK expression in non-malignant immune cells of the microenvironment mediates CLL development and progression in vivo. American Society of Hematology. 58th Annual Meeting; 2016 Dec 3–5; San Diego, CA.
  • Melcher M, Unger B, Schmidt U, et al. Essential roles for the Tec family kinases Tec and Btk in M-CSF receptor signaling pathways that regulate macrophage survival. J Immunol. 2008;180:8048–8056.

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