Ibrutinib, idelalisib and obinutuzumab for the treatment of patients with chronic lymphocytic leukemia: Three new arrows aiming at the target

Leukemia and Lymphoma

Volumn 56, Issue 12, 2015, Pages 3250-3256

  Morabito, Fortunato ^a   Gentile, Massimo ^a   Seymour, John F ^b   Polliack, Aaron ^c  

^a Azienda Ospedaliera di Cosenza   (Italy)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

Chronic lymphocytic leukemia; CLL; ibrutinib; idelalisib; obinutuzumab; targeted therapy

Indexed keywords

B LYMPHOCYTE RECEPTOR; CHLORAMBUCIL; IBRUTINIB; IDELALISIB; OBINUTUZUMAB; AGAMMAGLOBULINAEMIA TYROSINE KINASE; ANTINEOPLASTIC AGENT; CD20 ANTIGEN; MONOCLONAL ANTIBODY; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE 3 KINASE; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE; PURINE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE; QUINAZOLINONE DERIVATIVE;

CANCER COMBINATION CHEMOTHERAPY; CANCER IMMUNOTHERAPY; CANCER PATIENT; CHRONIC LYMPHATIC LEUKEMIA; DISEASE COURSE; DRUG EFFICACY; DRUG MECHANISM; DRUG SAFETY; FOLLOW UP; GENE DELETION; HUMAN; MAXIMUM TOLERATED DOSE; MONOTHERAPY; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; REVIEW; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL (TOPIC); LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; METABOLISM; MOLECULARLY TARGETED THERAPY; MORTALITY; TREATMENT OUTCOME;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTIGENS, CD20; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; CLINICAL TRIALS AS TOPIC; HUMANS; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MOLECULAR TARGETED THERAPY; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; PURINES; PYRAZOLES; PYRIMIDINES; QUINAZOLINONES; TREATMENT OUTCOME;

EID: 84948713791     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2015.1061193     Document Type: Review

References (56)

1. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med 2005; 352: 804-815.
2. Keating MJ, OBrien 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.
3. 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.
4. Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2012; 30: 3209-3216.
5. Robak T. New horizons in the treatment of chronic lymphocytic leukemia. Acta Haematol Pol 2014; 45: 122-131.
6. 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.
7. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014; 370: 997-1007.
8. 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.
9. Byrd JC, Brown JR, OBrien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014; 371: 213-223.
10. Cartron G, de Guibert S, Dilhuydy MS, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood 2014; 124: 2196-2202.
11. Pleyer L, Egle A, Hartmann N, et al. Molecular and cellular mechanisms of CLL: novel therapeutic approaches. Nat Rev Clin Oncol 2009; 6: 405-418.
12. Niiro H, Clark EA. RegulatiAn of B-Rell fate by Antigen-Rceptor signals. Nat Rev Immunol 2002; 2: 945-956.
13. Auentes-Ranana EM, Bannish G, Monroe JG. Basal B-cell receptor signaling in B lymphocytes: mechanisms of regulation and role in positive selection, differentiation, and peripheral survival. Immunol Rev 2003; 21: 841-894.
14. Stevenson FK, Caligaris-Cappio F. Chronic lymphocytic leukemia. Revelations from the B-cell receptor. Blood 2004; 103: 4389-4395.
15. Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer 2005; 5: 251-262.
16. Lenz G, Staudt LM. Aggressive lymphomas. N Eng J Med 2010; 362: 1417-1429.
17. Avalos AM, Meyer-Wentrup F, Ploegh HL. B-cell receptor signaling in lymphoid malignancies and autoimmunity. Adv Immunol 2014; 123: 1-49.
18. 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.
19. Honigberg LA, Smith AM, Sirisawad M, et al. 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: 13075-13080.
20. 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.
21. Chang BY, Francesco M, De Rooij MF, et al. Egress of CD19(+)CD5(+) cells into peripheral blood following treatment with the Bruton tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma patients. Blood 2013; 122: 2412-2424.
22. Advani RH, Buggy JJ, Sharman JP, et al. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol 2013; 31: 88-94.
23. Kamel S, Horton L, Ysebaert L, et al. Ibrutinib inhibits Collagen-Mediated but not ADP-mediated platelet aggregation. Leukemia 2015; 29: 783-787.
24. Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naïve and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015; 125: 2497-2506.
25. Woyach JA, Furman RR, Liu TM, et al. Resistance mechanisms for the Brutons tyrosine kinase inhibitor ibrutinib. N Engl J Med 2014; 370: 2286-2294.
26. OBrien S, Furman RR, Coutre SE, et al. 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: 48-58.
27. Byrd JC, Brown JR, OBrien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014; 371: 213-223.
28. 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.
29. Burger JA, Keating MJ, Wierda WG, et al. Ibrutinib in combination with rituximab is well tolerated and induces a high rate of durable remissions in patients with high-risk chronic lymphocytic leukemia: new, updated results of a phase II trial in 40 patients. Blood (ASH Annual Meeting Abstracts) 2013; 122: 675.
30. Brown JR, Barrientos JC, Barr PM, et al. Ibrutinib in combination with bendamustine and rituximab is active and tolerable in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: final results of a phase 1b study. Blood 2013; 122 (Suppl): 525 (Abstr).
31. Brown JR, Barrientos JC, Barr PM, et al. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood 2015; 125: 2915-2922.
32. Jain P, Keating M, Wierda W, et al. Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Blood 2015; 125: 2062-2067.
33. Okkenhaug K, Vanhaesebroeck B. PI3K in lymphocyte development, differentiation and activation. Nat Rev Immunol 2003; 3: 317-330.
34. Srinivasan L, Sasaki Y, Calado DP, et al. PI3 kinase signals BCR-dependent mature B cell survival. Cell 2009; 139: 573-586.
35. 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.
36. Barragan M, Bellosillo B, Campas C, et al. Involvement of protein kinase C and phosphatidylinositol 3-kinase pathways in the survival of B-cell chronic lymphocytic leukemia cells. Blood 2002; 99: 2969-2976.
37. 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.
38. Brown R, Furman RR, Flinn I, et al. Final results of a phase I study of idelalisib (GSE 1101) a selective inhibitor of PI3K{delta}, in patients with relapsed or refractory CLL. J Clin Oncol (ASCO Annual Meeting Abstracts) 2013; 31: 7003.
39. Barrientos JC, Furmann RR, Leonard J, et al. Update on a phase I study of the selective PI3K {delta} inhibitor idelalisib (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory CLL. J Clin Oncol 2013; 31 (Suppl): 7017 (Abstr).
40. 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.
41. Lannutti BJ, Meadows SA, Herman SE, et al. 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: 591-594.
42. Cheson BD, Byrd JC, Rai KR, et al. Novel targeted agents and the need to refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol 2012; 30: 2820-2822.
43. Hallek M, Cheson BD, Catovsky D, et al. Response assessment in chronic lymphocytic leukemia treated with novel agents causing an increase of peripheral blood lymphocytes. Blood 2012; 119: 5348.
44. Barrientos JC, Furman RR, Leonard J, et al. Update on a phase I study of the selective PI3Kδ inhibitor idelalisib (GS-1101) in combination with rituximab and/or bendamustine in patients with relapsed or refractory CLL. J Clin Oncol (ASCO Annual Meeting Abstracts) 2013; 31: 7017.
45. Wagner-Johnston ND, de Vos S, Coutre SE, et al. Chemoimmunotherapy combination of idelalisib with bendamustine/rituximab or chlorambucil/rituximab in patients with relapsed/refractory CLL demonstrates efficacy and tolerability. Blood (ASH Annual Meeting Abstracts) 2013; 122: 4176.
46. de Vos S, Furman RR, Barrientos JC, et al. Idelalisib, a selective inhibitor of PI3Kδ, in combination with bendamustine, fludarabine or chlorambucil in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL). Blood (ASH Annual Meeting Abstracts) 2013; 122: 2878.
47. Coutre S, Leonard J, Furman R, et al. Update on a phase 1 study of the selective PI3K-delta inhibitor, idelalisib (GS-1101) in combination with ofatumumab in patients with relapsed or refractory chronic lymphocytic leukemia. Haematologica 2013; 98 (Suppl):(Abstr S1150).
48. de Vos S, Leonard JP, Barrientos JC, et al. A phase 1 study of the selective PI3Kδ inhibitor idelalisib (GS-1101) in combination with therapeutic anti-CD20 antibodies (rituximab or ofatumumab) in patients with relapsed or refractory chronic lymphocytic leukemia. Blood (ASH Annual Meeting Abstracts) 2013; 122: 4180.
49. OBrien SM, Lamanna N, Kipps TJ, et al. A phase II study of the selective phosphatidylinositol 3-kinase delta (PI3Kd) inhibitor idelalisib (GS-1101) in combination with rituximab in treatment-naive patients > 65 years with chronic lymphocytic leukemia or small lymphocytic lymphoma. J Clin Oncol (ASCO Annual Meeting Abstracts) 2013; 31: 7005.
50. Maloney DG. Anti-CD20 antibody therapy for B-cell lymphomas. N Engl J Med 2012; 366: 2008-2016.
51. Beers SA, Chan CH, French RR, et al. CD20 as a target for therapeutic type I and II monoclonal antibodies. Semin Hematol 2010; 47: 107-114.
52. Mossner E, Brunker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity. Blood 2010; 115: 4393-4402.
53. Alduaij W, Ivanov A, Honeychurch J, et al. Novel type II anti-CD20 monoclonal antibody (GA101) evokes homotypic adhesion and actin-dependent, lysosome-mediated cell death in B-cell malignancies. Blood 2011; 117: 4519-4529.
54. Morschhauser F, Cartron G, Lamy T, et al. Phase I study of RO5072759 (GA101) in relapsed/refractory chronic lymphocytic leukemia. Blood (ASH Annual Meeting Abstracts) 2009; 114: 884.
55. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014; 370: 1101-1110.
56. Brown JR, OBrien S, Kingsley CD, et al. Obinutuzumab (G) plus fludarabine/cyclophosphamide (G-FC) or bendamustine (G-B) in the initial therapy of CLL patients: the phase 1b GALTON trial. Blood 2015; 125: 2779-2785.