REFERENCES
2. Rossi D, Gaidano G. The clinical implications of gene mutations in chronic lymphocytic leukaemia. Br J Cancer 2016;114:849-54.
3. Rossi D, Terzi-di-Bergamo L, De Paoli L, Cerri M, Ghilardi G, et al. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood 2015;126:1921-4.
4. Condoluci A, Rossi D. Clonal evolution in chronic lymphocytic leukemia. Clinical Lymphoma Myeloma Leukemia 2019;19:S16-9.
5. Tsimberidou AM, Tam C, Abruzzo LV, O’Brien S, Wierda WG, et al. Chemoimmunotherapy may overcome the adverse prognostic significance of 11q deletion in previously untreated patients with chronic lymphocytic leukemia. Cancer 2009;115:373-80.
6. Stilgenbauer S, Schnaiter A, Paschka P, Zenz T, Rossi M, et al. Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial. Blood 2014;123:3247-54.
7. Spunarova M, Tom N, Pavlova S, Mraz M, Brychtova Y, et al. Impact of gene mutations and chromosomal aberrations on progression-free survival in chronic lymphocytic leukemia patients treated with front-line chemoimmunotherapy: clinical practice experience. Leuk Res 2019;81:75-81.
8. Landau DA, Tausch E, Taylor-Weiner AN, Stewart C, Reiter JG, et al. Mutations driving CLL and their evolution in progression and relapse. Nature 2015;526:525-30.
9. Badoux XC, Keating MJ, Wang X, O’Brien SM, Ferrajoli A, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood 2011;117:3016-24.
10. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet 2010;376:1164-74.
11. Keating MJ, O’Brien S, Albitar M, Lerner S, Plunkett W, et al. Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia. J Clin Oncol 2005;23:4079-88.
12. Wierda W, O’Brien S, Wen S, Faderl S, Garcia-Manero G, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol 2005;23:4070-8.
13. Thompson PA, Tam CS, O’Brien SM, Wierda WG, Stingo F, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood 2016;127:303-9.
14. Benjamini O, Jain P, Trinh L, Qiao W, Strom SS, et al. Second cancers in patients with chronic lymphocytic leukemia who received frontline fludarabine, cyclophosphamide and rituximab therapy: distribution and clinical outcomes. Leuk Lymphoma 2015;56:1643-50.
15. Deans JP, Li H, Polyak MJ. CD20-mediated apoptosis: signalling through lipid rafts. Immunology 2002;107:176-82.
16. Alomari M, Mactier S, Kaufman KL, Best OG, Mulligan SP, et al. Profiling the lipid raft proteome from human MEC1 chronic lymphocytic leukemia cells. J Proteom Bioinform 2014;S7:005.
17. Hammadi M, Youinou P, Tempescul A, Tobón G, Berthou C, et al. Membrane microdomain sphingolipids are required for anti-CD20-induced death of chronic lymphocytic leukemia B cells. Haematologica 2012;97:288-96.
18. Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood 2016;127:208-15.
19. Brieghel C, Kinalis S, Yde CW, Schmidt AY, Jønson L, et al. Deep targeted sequencing of TP53 in chronic lymphocytic leukemia: clinical impact at diagnosis and at time of treatment. Haematologica 2019;104:789-96.
20. Ferracin M, Zagatti B, Rizzotto L, Cavazzini F, Veronese A, et al. MicroRNAs involvement in fludarabine refractory chronic lymphocytic leukemia. Mol Cancer 2010;9:123.
21. Gagez AL, Duroux-Richard I, Leprêtre S, Orsini-Piocelle F, Letestu R, et al. miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study. Haematologica 2017;102:746-54.
22. Cerna K, Oppelt J, Chochola V, Musilova K, Seda V, et al. MicroRNA miR-34a downregulates FOXP1 during DNA damage response to limit BCR signalling in chronic lymphocytic leukaemia B cells. Leukemia 2019;33:403-14.
23. Pozzo F, Bittolo T, Arruga F, Bulian P, Macor P, et al. NOTCH1 mutations associate with low CD20 level in chronic lymphocytic leukemia: evidence for a NOTCH1 mutation-driven epigenetic dysregulation. Leukemia 2016;30:182-9.
24. Tausch E, Beck P, Schlenk RF, Jebaraj BJ, Dolnik A, et al. Prognostic and predictive role of gene mutations in chronic lymphocytic leukemia: results from the pivotal phase III study COMPLEMENT1. Haematologica 2020. Epub ahead of print. doi: 10.3324/haematol.2019.229161
25. Edelmann J, Tausch E, Landau DA, Robrecht S, Bahlo J, et al. Frequent evolution of copy number alterations in CLL following first-line treatment with FC(R) is enriched with TP53 alterations: results from the CLL8 trial. Leukemia 2017;31:734-8.
26. Baliakas P, Jeromin S, Iskas M, Puiggros A, Plevova K, et al. Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact. Blood 2019;133:1205-16.
27. Guièze R, Robbe P, Clifford R, de Guibert S, Pereira B, et al. Presence of multiple recurrent mutations confers poor trial outcome of relapsed/refractory CLL. Blood 2015;126:2110-7.
28. Fischer K, Cramer P, Busch R, Stilgenbauer S, Bahlo J, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol 2011;29:3559-66.
29. Teeling JL, French RR, Cragg MS, van den Brakel J, Pluyter M, et al. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 2004;104:1793-800.
30. Bologna L, Gotti E, Da Roit F, Intermesoli T, Rambaldi A, et al. Ofatumumab is more efficient than rituximab in lysing B chronic lymphocytic leukemia cells in whole blood and in combination with chemotherapy. J Immunol 2013;190:231-9.
31. Cartron G, de Guibert S, Dilhuydy MS, Morschhauser F, Leblond V, et al. Obinutuzumab (GA101) in relapsed/refractory chronic lymphocytic leukemia: final data from the phase 1/2 GAUGUIN study. Blood 2014;124:2196-202.
32. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 2014;370:1101-10.
33. Ysebaert L, Laprévotte E, Klein C, Quillet-Mary A. Obinutuzumab (GA101) is highly effective against chronic lymphocytic leukemia cells in ex vivo B-cell depletion irrespective of high-risk prognostic markers. Blood Cancer J 2015;5:e367.
34. Burger JA, Chiorazzi N. B cell receptor signaling in chronic lymphocytic leukemia. Trends Immunol 2013;34:592-601.
35. Burger JA, Gribben JG. The microenvironment in chronic lymphocytic leukemia (CLL) and other B cell malignancies: insight into disease biology and new targeted therapies. Semin Cancer Biol 2014;24:71-81.
36. Chen SS, Chang BY, Chang S, Tong T, Ham S, et al. BTK inhibition results in impaired CXCR4 chemokine receptor surface expression, signaling and function in chronic lymphocytic leukemia. Leukemia 2016;30:833-43.
37. Pavlasova G, Borsky M, Seda V, Cerna K, Osickova J, et al. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood 2016;128:1609-13.
38. Herman SEM, Mustafa RZ, Jones J, Wong DH, Farooqui M, et al. Treatment with ibrutinib inhibits BTK- and VLA-4-dependent adhesion of chronic lymphocytic leukemia cells in vivo. Clin Cancer Res 2015;21:4642-51.
39. Kapoor I, Li Y, Sharma A, Zhu H, Bodo J, et al. Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies. Cell Death Dis 2019;10:924.
40. Pan Z, Scheerens H, Li SJ, Schultz BE, Sprengeler PA, et al. Discovery of selective irreversible inhibitors for Bruton’s tyrosine kinase. Chem Med Chem 2007;2:58-61.
41. Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. N Engl J Med 2015;373:2425-37.
42. Byrd JC, Brown JR, O’Brien S, Barrientos JC, Kay NE, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med 2014;371:213-23.
43. Stephens DM, Byrd JC. How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia. Blood 2019;133:1298-307.
44. Mato AR, Nabhan C, Thompson MC, Lamanna N, Brander DM, et al. Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. Haematologica 2018;103:874-9.
45. Furman RR, Cheng S, Lu P, Setty M, Perez AR, et al. Ibrutinib resistance in chronic lymphocytic leukemia. N Engl J Med 2014;370:2352-4.
46. Woyach JA, Furman RR, Liu TM, Ozer HG, Zapatka M, et al. Resistance mechanisms for the Bruton’s tyrosine kinase inhibitor ibrutinib. N Engl J Med 2014;370:2286-94.
47. Kanagal-Shamanna R, Jain P, Patel KP, Routbort M, Bueso-Ramos C, et al. Targeted multigene deep sequencing of Bruton tyrosine kinase inhibitor-resistant chronic lymphocytic leukemia with disease progression and Richter transformation. Cancer 2019;125:559-74.
48. Sharma S, Galanina N, Guo A, Lee J, Kadri S, et al. Identification of a structurally novel BTK mutation that drives ibrutinib resistance in CLL. Oncotarget 2016;7:68833-41.
49. Quinquenel A, Fornecker LM, Letestu R, Ysebaert L, Fleury C, et al. Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after 3 years: a FILO group study. Blood 2019;134:641-4.
50. Sinha S, Price-Troska T, Tian S, Secreto CR, Wu X, et al. PD-1 Overexpression in richter’s transformation (RT) and aggressive chronic lymphocytic leukemia (CLL) after progression on ibrutinib increases Bcl-2 expression via Akt/mTOR pathway. Am Soc Hematology 2018.
51. Jain N, Havranek O, Singh RK, Khashab T, Shirazi F, et al. Overcoming ibrutinib resistance by targeting phosphatidylinositol-3-kinase signaling in diffuse large B-cell lymphoma. bioRxiv 2019:523761.
52. Del Poeta G, Postorino M, Pozzo F, Del Principe MI, Santinelli E, et al. The amount of apoptosis predicts outcome in ibrutinib-treated chronic lymphocytic leukemia (CLL). Blood 2018;132 (Supplement 1):4397.
53. Tissino E, Benedetti D, Herman SEM, Ten Hacken E, Ahn IE, et al. Functional and clinical relevance of VLA-4 (CD49d/CD29) in ibrutinib-treated chronic lymphocytic leukemia. J Exp Med 2018;215:681-97.
54. Hillmen P, Rawstron A, Brock K, Munoz Vicente S, Yates F, et al. Ibrutinib plus venetoclax in relapsed/refractory CLL: results of the bloodwise TAP clarity study. Blood 2018;132 (Supplement 1):182.
55. Davids MS, Kim HT, Nicotra A, Savell A, Francoeur K, et al; Blood Cancer Research Partnership of the Leukemia and Lymphoma Society. Umbralisib in combination with ibrutinib in patients with relapsed or refractory chronic lymphocytic leukaemia or mantle cell lymphoma: a multicentre phase 1-1b study. Lancet Haematol 2019;6:e38-47.
56. Wang M, Rule S, Zinzani PL, Goy A, Casasnovas O, et al. Acalabrutinib in relapsed or refractory mantle cell lymphoma (ACE-LY-004): a single-arm, multicentre, phase 2 trial. Lancet 2018;391:659-67.
57. Tam C, Grigg AP, Opat S, Ku M, Gilbertson M, et al. The BTK inhibitor, Bgb-3111, is safe, tolerable, and highly active in patients with relapsed/refractory B-cell malignancies: initial report of a phase 1 first-in-human trial. Blood 2015;126.
58. Walter HS, Rule SA, Dyer MJ, Karlin L, Jones C, et al. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood 2016;127:411-9.
59. Montalban X, Arnold DL, Weber MS, Staikov I, Piasecka-Stryczynska K, et al; Evobrutinib Phase 2 Study Group. Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis. N Engl J Med 2019;380:2406-17.
60. Goess C, Harris CM, Murdock S, McCarthy RW, Sampson E, et al. ABBV-105, a selective and irreversible inhibitor of Bruton’s tyrosine kinase, is efficacious in multiple preclinical models of inflammation. Mod Rheumatol 2019;29:510-22.
61. Park JK, Byun JY, Park JA, Kim YY, Lee YJ, et al. HM71224, a novel Bruton’s tyrosine kinase inhibitor, suppresses B cell and monocyte activation and ameliorates arthritis in a mouse model: a potential drug for rheumatoid arthritis. Arthritis Res Ther 2016;18:91.
62. Liclican A, Serafini L, Xing W, Czerwieniec G, Steiner B, et al. Biochemical characterization of tirabrutinib and other irreversible inhibitors of Bruton’s tyrosine kinase reveals differences in on - and off - target inhibition. Biochim Biophys Acta Gen Subj 2020;1864:129531.
63. Brown JR, Barrientos JC, Barr PM, Flinn IW, Burger JA, et al. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood 2015;125:2915-22.
64. Lampson BL, Brown JR. Are BTK and PLCG2 mutations necessary and sufficient for ibrutinib resistance in chronic lymphocytic leukemia? Expert Rev Hematol 2018;11:185-94.
65. Brown JR, Byrd JC, Coutre SE, Benson DM, Flinn IW, et al. Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia. Blood 2014;123:3390-7.
66. Lampson BL, Kasar SN, Matos TR, Morgan EA, Rassenti L, et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood 2016;128:195-203.
67. Woyach JA, Johnson AJ. Targeted therapies in CLL: mechanisms of resistance and strategies for management. Blood 2015;126:471-7.
68. Scheffold A, Jebaraj BMC, Tausch E, Bloehdorn J, Ghia P, et al. IGF1R as druggable target mediating PI3K-δ inhibitor resistance in a murine model of chronic lymphocytic leukemia. Blood 2019;134:534-47.
69. Murali I, Kasar S, McWilliams EM, Itchaki G, Tyekucheva S, et al. Activating MAPK pathway mutations mediate primary resistance to PI3K inhibitors in chronic lymphocytic leukemia (CLL). Am Soc Hematology 2018; doi: 10.1182/blood-2018-99-115304.
70. Crassini K, Shen Y, Stevenson WS, Christopherson R, Ward C, et al. MEK1/2 inhibition by binimetinib is effective as a single agent and potentiates the actions of Venetoclax and ABT-737 under conditions that mimic the chronic lymphocytic leukaemia (CLL) tumour microenvironment. Br J Haematol 2018;182:360-72.
71. Flinn IW, Hillmen P, Montillo M, Nagy Z, Illés Á, et al. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood 2018;132:2446-55.
72. Kim JH, Kim WS, Park C. Interleukin-6 mediates resistance to PI3K-pathway-targeted therapy in lymphoma. BMC Cancer 2019;19:936.
73. Burris HA, Flinn IW, Patel MR, Fenske TS, Deng C, et al. Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study. Lancet Oncol 2018;19:486-96.
74. Friedberg JW, Sharman J, Sweetenham J, Johnston PB, Vose JM, et al. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 2010;115:2578-85.
75. Coffey GP, Feng J, Betz A, Pandey A, Birrell M, et al. Cerdulatinib Pharmacodynamics and Relationships to Tumor Response Following Oral Dosing in Patients with Relapsed/Refractory B-cell Malignancies. Clin Cancer Res 2019;25:1174-84.
76. Guo A, Lu P, Coffey G, Conley P, Pandey A, et al. Dual SYK/JAK inhibition overcomes ibrutinib resistance in chronic lymphocytic leukemia: Cerdulatinib, but not ibrutinib, induces apoptosis of tumor cells protected by the microenvironment. Oncotarget 2017;8:12953-67.
77. Hamlin PA, Farber CM, Fenske TS, Khatcheressian JL, Miller CB, et al. The dual SYK/JAK inhibitor cerdulatinib demonstrates rapid tumor responses in a phase 2 study in patients with relapsed/refractory B-and T-cell non-Hodgkin lymphoma (NHL). Hematological Oncol 2017;35:74.
78. Abrams ST, Lakum T, Lin K, Jones GM, Treweeke AT, et al. B-cell receptor signaling in chronic lymphocytic leukemia cells is regulated by overexpressed active protein kinase CbetaII. Blood 2007;109:1193-201.
79. Nakagawa R, Vukovic M, Tarafdar A, Cosimo E, Dunn K, et al. Generation of a poor prognostic chronic lymphocytic leukemia-like disease model: PKCα subversion induces up-regulation of PKCβII expression in B lymphocytes. Haematologica 2015;100:499-510.
81. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 2005;102:13944-9.
82. van Delft MF, Wei AH, Mason KD, Vandenberg CJ, Chen L, et al. The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 2006;10:389-99.
83. Gandhi L, Camidge DR, Ribeiro de Oliveira M, Bonomi P, Gandara D, et al. Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors. J Clin Oncol 2011;29:909-16.
84. Delbridge AR, Strasser A. The BCL-2 protein family, BH3-mimetics and cancer therapy. Cell Death Differ 2015;22:1071-80.
85. de Weerdt I, Hofland T, Dobber J, Dubois J, Eldering E, et al. First Evidence of Restoration of T and NK Cell Compartment after Venetoclax Treatment. Blood 2018;132 (Supplement 1):1860.
86. Anderson MA, Deng J, Seymour JF, Tam C, Kim SY, et al. The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism. Blood 2016;127:3215-24.
87. Kater AP, Seymour JF, Hillmen P, Eichhorst B, Langerak AW, et al. Fixed duration of venetoclax-rituximab in relapsed/refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the MURANO phase III study. J Clin Oncol 2019;37:269-77.
88. Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med 2016;374:311-22.
89. Herling CD, Abedpour N, Weiss J, Schmitt A, Jachimowicz RD, et al. Clonal dynamics towards the development of venetoclax resistance in chronic lymphocytic leukemia. Nat Commun 2018;9:727.
90. Blombery P, Anderson MA, Gong JN, Thijssen R, Birkinshaw RW, et al. Acquisition of the recurrent Gly101Val mutation in BCL2 confers resistance to venetoclax in patients with progressive chronic lymphocytic leukemia. Cancer Discov 2019;9:342-53.
91. Tausch E, Close W, Dolnik A, Bloehdorn J, Chyla B, et al. Venetoclax resistance and acquired BCL2 mutations in chronic lymphocytic leukemia. Haematologica 2019;104:e434-7.
92. Choudhary GS, Al-Harbi S, Mazumder S, Hill BT, Smith MR, et al. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis 2015;6:e1593.
93. Guièze R, Liu VM, Rosebrock D, Jourdain AA, Hernández-Sánchez M, et al. Mitochondrial reprogramming underlies resistance to BCL-2 inhibition in lymphoid malignancies. Cancer Cell 2019;36:369-84.e13.
94. Vogler M, Butterworth M, Majid A, Walewska RJ, Sun XM, et al. Concurrent up-regulation of BCL-XL and BCL2A1 induces approximately 1000-fold resistance to ABT-737 in chronic lymphocytic leukemia. Blood 2009;113:4403-13.
95. Punnoose EA, Leverson JD, Peale F, Boghaert ER, Belmont LD, et al. Expression profile of BCL-2, BCL-XL, and MCL-1 predicts pharmacological response to the BCL-2 selective antagonist venetoclax in multiple myeloma models. Mol Cancer Ther 2016;15:1132-44.
96. Touzeau C, Dousset C, Le Gouill S, Sampath D, Leverson JD, et al. The Bcl-2 specific BH3 mimetic ABT-199: a promising targeted therapy for t(11;14) multiple myeloma. Leukemia 2014;28:210-2.
97. Burger JA, Keating MJ, Wierda WG, Hartmann E, Hoellenriegel J, 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;15:1090-9.
98. Skarzynski M, Niemann CU, Lee YS, Martyr S, Maric I, et al. Interactions between ibrutinib and anti-CD20 antibodies: competing effects on the outcome of combination therapy. Clin Cancer Res 2016;22:86-95.
99. Jaglowski SM, Jones JA, Nagar V, Flynn JM, Andritsos LA, et al. Safety and activity of BTK inhibitor ibrutinib combined with ofatumumab in chronic lymphocytic leukemia: a phase 1b/2 study. Blood 2015;126:842-50.
100. Shanafelt TD, Wang XV, Kay NE, Hanson CA, O’Brien S, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med 2019;381:432-43.
101. Jones JA, Mato AR, Wierda WG, Davids MS, Choi M, et al. Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol 2018;19:65-75.
102. Hillmen P, Rawstron AC, Brock K, Muñoz-Vicente S, Yates FJ, et al. Ibrutinib plus venetoclax in relapsed/refractory chronic lymphocytic leukemia: the CLARITY study. J Clin Oncol 2019;37:2722-9.
103. Jain N, Keating M, Thompson P, Ferrajoli A, Burger J, et al. Ibrutinib and Venetoclax for First-Line Treatment of CLL. N Engl J Med 2019;380:2095-103.
104. O’Brien S, Furman RR, Coutre S, Flinn IW, Burger JA, et al. Single-agent ibrutinib in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood 2018;131:1910-9.
105. Fruman DA, Cantley LC. Idelalisib--a PI3Kδ inhibitor for B-cell cancers. N Engl J Med 2014;370:1061-2.
106. Lunning M, Vose J, Nastoupil L, Fowler N, Burger JA, et al. Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. Blood 2019;134:1811-20.
107. Mato AR, Roeker LE, Eyre TA, Nabhan C, Lamanna N, et al. A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R/R CLL. Blood Adv 2019;3:1568-73.
108. Thijssen R, Slinger E, Weller K, Geest CR, Beaumont T, et al. Resistance to ABT-199 induced by microenvironmental signals in chronic lymphocytic leukemia can be counteracted by CD20 antibodies or kinase inhibitors. Haematologica 2015;100:e302-6.
109. Jak M, van Bochove GG, van Lier RA, Eldering E, van Oers MH. CD40 stimulation sensitizes CLL cells to rituximab-induced cell death. Leukemia 2011;25:968-78.
110. Dobrovolsky D, Wang ES, Morrow S, Leahy C, Faust T, et al. Bruton tyrosine kinase degradation as a therapeutic strategy for cancer. Blood 2019;133:952-61.
111. Shen Y, Crassini K, Sandhu S, Fatima N, Christopherson RI, et al. Dual inhibition of MEK1/2 and AKT by binimetinib and MK2206 induces apoptosis of chronic lymphocytic leukemia cells under conditions that mimic the tumor microenvironment. Leuk Lymphoma 2019;60:1632-43.
112. Shen Y, Crassini KR, O’Dwyer ME, O’Neill MF, Christopherson R, et al. The dual PI3/PIM-kinase inhibitor, Ibl-202, is highly synergistic with venetoclax against CLL cells, and TP53-knock-out cells, and under conditions that mimic the tumor microenvironment. Blood 2018;132(Supplement 1):1870.
113. Tahir SK, Smith ML, Hessler P, Rapp LR, Idler KB, et al. Potential mechanisms of resistance to venetoclax and strategies to circumvent it. BMC Cancer 2017;17:399.
114. Ramsey HE, Fischer MA, Lee T, Gorska AE, Arrate MP, et al. A novel MCL1 inhibitor combined with venetoclax rescues venetoclax-resistant acute myelogenous leukemia. Cancer Discov 2018;8:1566-81.
115. Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood 2017;129:3419-27.
116. Herrera AF, Goy A, Mehta A, Ramchandren R, Pagel JM, et al. Safety and activity of ibrutinib in combination with durvalumab in patients with relapsed or refractory follicular lymphoma or diffuse large B-cell lymphoma. Am J Hematol 2020;95:18-27.
117. Gao C, Peng YN, Wang HZ, Fang SL, Zhang M, et al. Inhibition of heat shock protein 90 as a novel platform for the treatment of cancer. Curr Pharm Des 2019;25:849-55.
118. Crassini K, Shen Y, O’Dwyer M, O’Neill M, Christopherson R, et al. The dual inhibitor of the phosphoinositol-3 and PIM kinases, IBL-202, is effective against chronic lymphocytic leukaemia cells under conditions that mimic the hypoxic tumour microenvironment. Br J Haematol 2018;182:654-69.
119. Ljungström V, Cortese D, Young E, Pandzic T, Mansouri L, et al. Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations. Blood 2016;127:1007-16.
120. Chai-Adisaksopha C, Brown JR. FCR achieves long-term durable remissions in patients with IGHV-mutated CLL. Blood 2017;130:2278-82.
121. Fischer K, Cramer P, Busch R, Böttcher S, Bahlo J, 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;30:3209-16.
122. Eichhorst B, Fink AM, Bahlo J, Busch R, Kovacs G, 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;17:928-42.