Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: A single-arm, phase 2 study

The Lancet Oncology

Volumn 15, Issue 10, 2014, Pages 1090-1099

  Burger, Jan A ^a   Keating, Michael J ^a   Wierda, William G ^a   Hartmann, Elena ^b   Hoellenriegel, Julia ^a   Rosin, Nathalie Y ^a   de Weerdt, Iris ^a   Jeyakumar, Ghayathri ^a   Ferrajoli, Alessandra ^a   Cardenas Turanzas, Marylou ^a   Lerner, Susan ^a   Jorgensen, Jeffrey L ^a   Nogueras González, Graciela M ^a   Zacharian, Gracy ^a   Huang, Xuelin ^a   Kantarjian, Hagop ^a   Garg, Naveen ^a   Rosenwald, Andreas ^b   O'Brien, Susan ^a  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; BETA 2 MICROGLOBULIN; CD72 ANTIGEN; CXCL13 CHEMOKINE; EARLY GROWTH RESPONSE FACTOR 1; EARLY GROWTH RESPONSE FACTOR 2; EARLY GROWTH RESPONSE FACTOR 3; IBRUTINIB; IMMUNOGLOBULIN M; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 3BETA; PROTEIN P53; RITUXIMAB; SECONDARY LYMPHOID TISSUE CHEMOKINE; STROMAL CELL DERIVED FACTOR 1; TUMOR NECROSIS FACTOR ALPHA; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE;

ADULT; AGED; ALOPECIA; AMINOTRANSFERASE BLOOD LEVEL; ANEMIA; ANXIETY DISORDER; ARTHRALGIA; ARTICLE; BLEEDING; BONE PAIN; CANCER COMBINATION CHEMOTHERAPY; CANCER RISK; CANCER SURVIVAL; CCL3 GENE; CD72 GENE; CHRONIC LYMPHATIC LEUKEMIA; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL ARTICLE; CONSTIPATION; DIARRHEA; DOWN REGULATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; EGR1 GENE; EGR2 GENE; EGR3 GENE; EPIPHORA; FATIGUE; FEMALE; GASTROESOPHAGEAL REFLUX; GENE; GENE DELETION; GENE EXPRESSION REGULATION; HEADACHE; HEART ATRIUM FIBRILLATION; HIGH RISK PATIENT; HOT FLUSH; HUMAN; IMMUNOGLOBULIN BLOOD LEVEL; INSOMNIA; LUNG INFECTION; LYMPHOCYTE COUNT; MALE; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; MYALGIA; NAUSEA; NEUTROPENIA; OCULAR PRURITUS; OSTEOPOROSIS; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PERIPHERAL NEUROPATHY; PHASE 2 CLINICAL TRIAL; PNEUMONIA; PROGRESSION FREE SURVIVAL; QUALITY OF LIFE; RASH; SEPSIS; SIDE EFFECT; SKIN BRUISING; SUBDURAL HEMATOMA; SURVIVAL RATE; SURVIVAL TIME; TP53 GENE; UPPER RESPIRATORY TRACT INFECTION; UPREGULATION; URINARY TRACT INFECTION; VOMITING; WEIGHT GAIN; XEROSTOMIA; CLINICAL TRIAL; DISEASE FREE SURVIVAL; DOSE RESPONSE; DRUG ADMINISTRATION; KAPLAN MEIER METHOD; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MORTALITY; NEOPLASM RECURRENCE, LOCAL; ORAL DRUG ADMINISTRATION; PATIENT SELECTION; PROGNOSIS; TREATMENT OUTCOME; VERY ELDERLY;

ADMINISTRATION, ORAL; ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; KAPLAN-MEIER ESTIMATE; LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; PATIENT SELECTION; PROGNOSIS; PYRAZOLES; PYRIMIDINES; SURVIVAL RATE; TREATMENT OUTCOME;

EID: 84906855910     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(14)70335-3     Document Type: Article

References (37)

1. Hallek M Signaling the end of chronic lymphocytic leukemia: new frontline treatment strategies. Blood 2013, 122:3723-3734.
2. 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.
3. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med 2014, 370:997-1007.
4. 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.
5. Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000, 343:1910-1916.
6. 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.
7. 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.
8. Stilgenbauer S, Zenz T Understanding and managing ultra high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program 2010, 2010:481-488.
9. Dohner H, Stilgenbauer S, James MR, et al. 11q deletions identify a new subset of B-cell chronic lymphocytic leukemia characterized by extensive nodal involvement and inferior prognosis. Blood 1997, 89:2516-2522.
10. 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.
11. Burger JA, Buggy JJ Emerging drug profiles: Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Leuk Lymphoma 2013, 54:2385-2391.
12. 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.
13. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med 2013, 369:507-516.
14. FDA approves ibrutinib for chronic lymphocytic leukemia Cancer Network, (accessed Feb 14, 2014). http://www.cancernetwork.com/news/fda-approves-ibrutinib-chronic-lymphocytic-leukemia.
15. Byrd JC, Brown JR, O'Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014, 371:213-223.
16. Burger JA, Montserrat E Coming full circle: 70 years of chronic lymphocytic leukemia cell redistribution, from glucocorticoids to inhibitors of B-cell receptor signaling. Blood 2013, 121:1501-1509.
17. Woyach JA, Smucker K, Smith LL, et al. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. Blood 2014, 123:1810-1817.
18. Herman SE, Gordon AL, Hertlein E, et al. Bruton's 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. 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.
20. 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.
21. Hallek M, Cheson BD, Catovsky D, et al. 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, 111:5446-5456.
22. Rawstron AC, Villamor N, Ritgen M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007, 21:956-964.
23. 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.
24. Keating MJ, Flinn I, Jain V, et al. Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 2002, 99:3554-3561.
25. Byrd JC, Furman RR, Coutre SE, et al. The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765) promotes high response rate, durable remissions, and is tolerable in treatment naïve (TN) and relapsed or refractory (RR) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) patients including patients with high-risk (HR) disease: new and updated results of 116 patients in a phase Ib/II study. Blood 2012, 120. abstr 189.
26. O'Brien 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. 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.
28. Kohrt HE, Sagiv-Barfi I, Rafiq S, et al. Ibrutinib antagonizes rituximab-dependent NK cell-mediated cytotoxicity. Blood 2014, 123:1957-1960.
29. Rafiq S, Butchar JP, Cheney C, et al. Comparative assessment of clinically utilized CD20-directed antibodies in chronic lymphocytic leukemia cells reveals divergent NK cell, monocyte, and macrophage properties. J Immunol 2013, 190:2702-2711.
30. Stephens DM, Ruppert AS, Jones J, et al. Impact of targeted therapy on outcome of chronic lymphocytic leukemia patients with relapsed Del(17p13.1) karyotype at a single center. Leukemia 2014, 28:1365-1368.
31. Shanafelt TD, Bowen D, Venkat C, et al. Quality of life in chronic lymphocytic leukemia: an international survey of 1482 patients. Br J Haematol 2007, 139:255-264.
32. Eichhorst BF, Busch R, Obwandner T, Kuhn-Hallek I, Herschbach P, Hallek M Health-related quality of life in younger patients with chronic lymphocytic leukemia treated with fludarabine plus cyclophosphamide or fludarabine alone for first-line therapy: a study by the German CLL Study Group. J Clin Oncol 2007, 25:1722-1731.
33. Herishanu Y, Perez-Galan P, Liu D, et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood 2011, 117:563-574.
34. Burger JA, Quiroga MP, Hartmann E, et al. High-level expression of the T-cell chemokines CCL3 and CCL4 by chronic lymphocytic leukemia B cells in nurselike cell cocultures and after BCR stimulation. Blood 2009, 113:3050-3058.
35. Sivina M, Hartmann E, Kipps TJ, et al. CCL3 (MIP-1a) plasma levels and the risk for disease progression in chronic lymphocytic leukemia (CLL). Blood 2011, 117:1662-1669.
36. 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.
37. Burger JA Chemokines and chemokine receptors in chronic lymphocytic leukemia (CLL): from understanding the basics towards therapeutic targeting. Semin Cancer Biol 2010, 20:424-430.