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Erschienen in: memo - Magazine of European Medical Oncology 1/2015

01.04.2015 | short review

Clinical update: B-cell receptor kinase inhibitors in chronic lymphocytic leukemia

verfasst von: MD, PhD Lukas Weiss, MD Thomas Melchardt, MD Alexander Egle

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 1/2015

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Abstract

B-cell receptor (BCR) inhibitors represent an exciting new treatment modality in chronic lymphocytic leukemia (CLL). Currently, ibrutinib monotherapy as well as idelalisib in combination with rituximab are approved by the European Medical Agency for the treatment of all patients with relapsed/refractory CLL and for first-line treatment of patients with deletion 17p or TP53 mutation unsuitable for chemoimmunotherapy. The results of ongoing trials with these and other BCR inhibitors are expected to lay the basis for approval in further indications, but have to be awaited. Above all, BCR inhibitors have shown to be able to fill the gap of urgently needed therapies for the elderly and comorbid CLL patient as well as the CLL patient with deletion 17p. BCR inhibitors might also challenge the role of allogeneic stem cell transplantation in CLL in the future.
Literatur
1.
Zurück zum Zitat Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA, Buggy JJ. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29):13075–80. (doi:10.1073/pnas.1004594107. Epub 2010 Jul 6. PubMed PMID: 20615965; PubMed Central PMCID: PMC2919935). CrossRefPubMedCentralPubMed Honigberg LA, Smith AM, Sirisawad M, Verner E, Loury D, Chang B, Li S, Pan Z, Thamm DH, Miller RA, Buggy JJ. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci USA. 2010;107(29):13075–80. (doi:10.1073/pnas.1004594107. Epub 2010 Jul 6. PubMed PMID: 20615965; PubMed Central PMCID: PMC2919935). CrossRefPubMedCentralPubMed
2.
Zurück zum Zitat Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117(2):591–4. (doi:10.1182/blood-2010-03-275305. Epub 2010 Oct 19. PubMed PMID: 20959606; PubMed Central PMCID: PMC3694505). CrossRefPubMedCentralPubMed Lannutti BJ, Meadows SA, Herman SE, Kashishian A, Steiner B, Johnson AJ, Byrd JC, Tyner JW, Loriaux MM, Deininger M, Druker BJ, Puri KD, Ulrich RG, Giese NA. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood. 2011;117(2):591–4. (doi:10.1182/blood-2010-03-275305. Epub 2010 Oct 19. PubMed PMID: 20959606; PubMed Central PMCID: PMC3694505). CrossRefPubMedCentralPubMed
3.
Zurück zum Zitat OʹBrien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA, Grant B, Richards DA, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Izumi R, Hamdy A, Chang BY, Graef T, Clow F, Buggy JJ, James DF, Byrd JC. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48–58. (doi:10.1016/S1470-2045(13)70513-8. Epub 2013 Dec 10. PubMed PMID: 24332241; PubMed Central PMCID: PMC4134524). CrossRefPubMedCentralPubMed OʹBrien S, Furman RR, Coutre SE, Sharman JP, Burger JA, Blum KA, Grant B, Richards DA, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Izumi R, Hamdy A, Chang BY, Graef T, Clow F, Buggy JJ, James DF, Byrd JC. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48–58. (doi:10.1016/S1470-2045(13)70513-8. Epub 2013 Dec 10. PubMed PMID: 24332241; PubMed Central PMCID: PMC4134524). CrossRefPubMedCentralPubMed
4.
Zurück zum Zitat Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31(1):88–94. (doi:10.1200/JCO.2012.42.7906. Epub 2012 Oct 8. PubMed PMID: 23045577). CrossRefPubMed Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013;31(1):88–94. (doi:10.1200/JCO.2012.42.7906. Epub 2012 Oct 8. PubMed PMID: 23045577). CrossRefPubMed
5.
Zurück zum Zitat Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, OʹBrien S. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42. (doi:10.1056/NEJMoa1215637. Epub 2013 Jun 19. Erratum in: N Engl J Med. 2014 Feb 20;370(8):786. PubMed PMID: 23782158; PubMed Central PMCID: PMC3772525). CrossRefPubMedCentralPubMed Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, OʹBrien S. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42. (doi:10.1056/NEJMoa1215637. Epub 2013 Jun 19. Erratum in: N Engl J Med. 2014 Feb 20;370(8):786. PubMed PMID: 23782158; PubMed Central PMCID: PMC3772525). CrossRefPubMedCentralPubMed
6.
Zurück zum Zitat Byrd JC, Brown JR, OʹBrien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23. (doi:10.1056/NEJMoa1400376. Epub 2014 May 31. PubMed PMID: 24881631; PubMed Central PMCID: PMC4134521). CrossRefPubMedCentralPubMed Byrd JC, Brown JR, OʹBrien S, Barrientos JC, Kay NE, Reddy NM, Coutre S, Tam CS, Mulligan SP, Jaeger U, Devereux S, Barr PM, Furman RR, Kipps TJ, Cymbalista F, Pocock C, Thornton P, Caligaris-Cappio F, Robak T, Delgado J, Schuster SJ, Montillo M, Schuh A, de Vos S, Gill D, Bloor A, Dearden C, Moreno C, Jones JJ, Chu AD, Fardis M, McGreivy J, Clow F, James DF, Hillmen P; RESONATE Investigators. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–23. (doi:10.1056/NEJMoa1400376. Epub 2014 May 31. PubMed PMID: 24881631; PubMed Central PMCID: PMC4134521). CrossRefPubMedCentralPubMed
7.
Zurück zum Zitat Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, Ruppert AS, Xue L, Li DH, Steggerda SM, Versele M, Dave SS, Zhang J, Yilmaz AS, Jaglowski SM, Blum KA, Lozanski A, Lozanski G, James DF, Barrientos JC, Lichter P, Stilgenbauer S, Buggy JJ, Chang BY, Johnson AJ, Byrd JC. Resistance mechanisms for the Brutonʹs tyrosine kinase inhibitor ibrutinib. N Engl J Med. 2014;370(24):2286–94. (doi:10.1056/NEJMoa1400029. Epub 2014 May 28. PubMed PMID: 24869598; PubMed Central PMCID: PMC4144824). CrossRefPubMedCentralPubMed Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, Ruppert AS, Xue L, Li DH, Steggerda SM, Versele M, Dave SS, Zhang J, Yilmaz AS, Jaglowski SM, Blum KA, Lozanski A, Lozanski G, James DF, Barrientos JC, Lichter P, Stilgenbauer S, Buggy JJ, Chang BY, Johnson AJ, Byrd JC. Resistance mechanisms for the Brutonʹs tyrosine kinase inhibitor ibrutinib. N Engl J Med. 2014;370(24):2286–94. (doi:10.1056/NEJMoa1400029. Epub 2014 May 28. PubMed PMID: 24869598; PubMed Central PMCID: PMC4144824). CrossRefPubMedCentralPubMed
8.
Zurück zum Zitat Burger JA, Keating MJ, Wierda WG, Hoellenriegel J, Jeyakumar G, Ferrajoli A, Faderl SH, Cardenas-Turanzas M, Lerner S, Zacharian G, Huang X, Kantarjian H, OʹBrien S. Ibrutinib in combination with rituximab (iR) is well tolerated and induces a high rate of durable remissions in patients with high-risk chronic lymphocytic leukemia (CLL): new, updated results of a phase ii trial in 40 patients. Blood. 2013;122. (ASH Meeting 2013; abstra 675) Burger JA, Keating MJ, Wierda WG, Hoellenriegel J, Jeyakumar G, Ferrajoli A, Faderl SH, Cardenas-Turanzas M, Lerner S, Zacharian G, Huang X, Kantarjian H, OʹBrien S. Ibrutinib in combination with rituximab (iR) is well tolerated and induces a high rate of durable remissions in patients with high-risk chronic lymphocytic leukemia (CLL): new, updated results of a phase ii trial in 40 patients. Blood. 2013;122. (ASH Meeting 2013; abstra 675)
9.
Zurück zum Zitat Brown JR, Barrientos JC, Barr PM, Flinn I, Burger JA, Salman Z, Clow F, James DF, Graef T, Friedberg J, Rai KR, OʹBrien S. Ibrutinib in combination with bendamustine and rituximab is active and tolerable in patients with relapsed/refractory CLL/SLL: final results of a phase 1b study. Blood. 2013;122. (ASH Meeting 2013; abstr 525) Brown JR, Barrientos JC, Barr PM, Flinn I, Burger JA, Salman Z, Clow F, James DF, Graef T, Friedberg J, Rai KR, OʹBrien S. Ibrutinib in combination with bendamustine and rituximab is active and tolerable in patients with relapsed/refractory CLL/SLL: final results of a phase 1b study. Blood. 2013;122. (ASH Meeting 2013; abstr 525)
10.
Zurück zum Zitat Brown JR, Furman RR, Flinn I, Coutre SE, Wagner-Johnston ND, Kahl BS, Spurgeon SEF, Benson DM, Peterman S, Johnson DM, Li D, Dansey RD, Jahn TM, Byrd JC. Final results of a phase I study of idelalisib (GSE1101) a selective inhibitor of PI3K{delta}, in patients with relapsed or refractory CLL. ASCO Meeting Abstracts, June 17, 2013:7003. Brown JR, Furman RR, Flinn I, Coutre SE, Wagner-Johnston ND, Kahl BS, Spurgeon SEF, Benson DM, Peterman S, Johnson DM, Li D, Dansey RD, Jahn TM, Byrd JC. Final results of a phase I study of idelalisib (GSE1101) a selective inhibitor of PI3K{delta}, in patients with relapsed or refractory CLL. ASCO Meeting Abstracts, June 17, 2013:7003.
11.
Zurück zum Zitat Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, OʹBrien SM. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007. (doi:10.1056/NEJMoa1315226. Epub 2014 Jan 22. PubMed PMID: 24450857). CrossRefPubMedCentralPubMed Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, Barrientos JC, Zelenetz AD, Kipps TJ, Flinn I, Ghia P, Eradat H, Ervin T, Lamanna N, Coiffier B, Pettitt AR, Ma S, Stilgenbauer S, Cramer P, Aiello M, Johnson DM, Miller LL, Li D, Jahn TM, Dansey RD, Hallek M, OʹBrien SM. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007. (doi:10.1056/NEJMoa1315226. Epub 2014 Jan 22. PubMed PMID: 24450857). CrossRefPubMedCentralPubMed
13.
Zurück zum Zitat Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446–56. (doi:10.1182/blood-2007-06-093906. Epub 2008 Jan 23. Erratum in: Blood. 2008 Dec 15;112(13):5259. PubMed PMID: 18216293; PubMed Central PMCID: PMC2972576). Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Döhner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008;111(12):5446–56. (doi:10.1182/blood-2007-06-093906. Epub 2008 Jan 23. Erratum in: Blood. 2008 Dec 15;112(13):5259. PubMed PMID: 18216293; PubMed Central PMCID: PMC2972576).
14.
Zurück zum Zitat Woyach JA, Smucker K, Smith LL, Lozanski A, Zhong Y, Ruppert AS, Lucas D, Williams K, Zhao W, Rassenti L, Ghia E, Kipps TJ, Mantel R, Jones J, Flynn J, Maddocks K, OʹBrien S, Furman RR, James DF, Clow F, Lozanski G, Johnson AJ, Byrd JC. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. Blood. 2014;123(12):1810–7. (doi:10.1182/blood-2013-09-527853. Epub 2014 Jan 10. PubMed PMID: 24415539; PubMed Central PMCID: PMC3962160). CrossRefPubMedCentralPubMed Woyach JA, Smucker K, Smith LL, Lozanski A, Zhong Y, Ruppert AS, Lucas D, Williams K, Zhao W, Rassenti L, Ghia E, Kipps TJ, Mantel R, Jones J, Flynn J, Maddocks K, OʹBrien S, Furman RR, James DF, Clow F, Lozanski G, Johnson AJ, Byrd JC. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. Blood. 2014;123(12):1810–7. (doi:10.1182/blood-2013-09-527853. Epub 2014 Jan 10. PubMed PMID: 24415539; PubMed Central PMCID: PMC3962160). CrossRefPubMedCentralPubMed
15.
Zurück zum Zitat Dreger P, Schetelig J, Andersen N, Corradini P, van Gelder M, Gribben J, Kimby E, Michallet M, Moreno C, Stilgenbauer S, Montserrat E. Managing high-risk chronic lymphocytic leukemia during transition to a new treatment era: stem cell transplantation or novel agents? Blood. 2014 Oct 9. pii: blood-2014–07-586826. [Epub ahead of print] PubMed PMID: 25301705. Dreger P, Schetelig J, Andersen N, Corradini P, van Gelder M, Gribben J, Kimby E, Michallet M, Moreno C, Stilgenbauer S, Montserrat E. Managing high-risk chronic lymphocytic leukemia during transition to a new treatment era: stem cell transplantation or novel agents? Blood. 2014 Oct 9. pii: blood-2014–07-586826. [Epub ahead of print] PubMed PMID: 25301705.
Metadaten
Titel
Clinical update: B-cell receptor kinase inhibitors in chronic lymphocytic leukemia
verfasst von
MD, PhD Lukas Weiss
MD Thomas Melchardt
MD Alexander Egle
Publikationsdatum
01.04.2015
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 1/2015
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-014-0186-0

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