Targeted Treatment of Chronic Lymphocytic Leukemia: Clinical Utility of Acalabrutinib

References

• SEER cancer statistics. Available from: https://seer.cancer.gov/statfacts/html/clyl.html. Accessed August 17, 2021.
   Google Scholar
• Niemann CU, Wiestner A. B-cell receptor signaling as a driver of lymphoma development and evolution. Semin Cancer Biol. 2013;23(6):410–421. doi:10.1016/j.semcancer.2013.09.001
   PubMed Web of Science ®Google Scholar
• Munir T, Brown JR, O’Brien S, et al. Final analysis from RESONATE: up to six years of follow-up on ibrutinib in patients with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma. Am J Hematol. 2019;94(12):1353–1363. doi:10.1002/ajh.25638
   PubMed Web of Science ®Google Scholar
• Burger JA, Barr PM, Robak T, et al. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020;34(3):787–798. doi:10.1038/s41375-019-0602-x
   PubMed Web of Science ®Google Scholar
• Woyach JA, Ruppert AS, Heerema NA, et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med. 2018;379(26):2517–2528. doi:10.1056/NEJMoa1812836
   PubMed Web of Science ®Google Scholar
• Moreno C, Greil R, Demirkan F, et al. Ibrutinib plus obinutuzumab versus chlorambucil plus obinutuzumab in first-line treatment of chronic lymphocytic leukaemia (iLLUMINATE): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019;20(1):43–56. doi:10.1016/S1470-2045(18)30788-5
   PubMed Web of Science ®Google Scholar
• Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-rituximab or chemoimmunotherapy for chronic lymphocytic leukemia. N Engl J Med. 2019;381(5):432–443. doi:10.1056/NEJMoa1817073
   PubMed Web of Science ®Google Scholar
• Caron F, Leong DP, Hillis C, Fraser G, Siegal D. Current understanding of bleeding with ibrutinib use: a systematic review and meta-analysis. Blood Adv. 2017;1(12):772–778. doi:10.1182/bloodadvances.2016001883
   PubMed Web of Science ®Google Scholar
• Ganatra S, Sharma A, Shah S, et al. Ibrutinib-associated atrial fibrillation. JACC Clin Electrophysiol. 2018;4(12):1491–1500. doi:10.1016/j.jacep.2018.06.004
   PubMedGoogle Scholar
• Caldeira D, Alves D, Costa J, Ferreira JJ, Pinto FJ. Ibrutinib increases the risk of hypertension and atrial fibrillation: systematic review and meta-analysis. PLoS One. 2019;14(2):e0211228. doi:10.1371/journal.pone.0211228
   PubMed Web of Science ®Google Scholar
• Barr PM, Brown JR, Hillmen P, et al. Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL. Blood. 2017;129(19):2612–2615. doi:10.1182/blood-2016-12-737346
   PubMed Web of Science ®Google Scholar
• 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 U S A. 2010;107(29):13075–13080. doi:10.1073/pnas.1004594107
   PubMed Web of Science ®Google Scholar
• Byrd JC, Harrington B, O’Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):323–332. doi:10.1056/NEJMoa1509981
   PubMed Web of Science ®Google Scholar
• Herman SEM, Montraveta A, Niemann CU, et al. The Bruton Tyrosine Kinase (BTK) inhibitor acalabrutinib demonstrates potent on-target effects and efficacy in two mouse models of chronic lymphocytic leukemia. Clin Cancer Res. 2017;23(11):2831–2841. doi:10.1158/1078-0432.CCR-16-0463
   PubMed Web of Science ®Google Scholar
• Barf T, Covey T, Izumi R, et al. Acalabrutinib (ACP-196): a covalent Bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. J Pharmacol Exp Ther. 2017;363(2):240–252. doi:10.1124/jpet.117.242909
   PubMed Web of Science ®Google Scholar
• Kaptein A, de Bruin G, Emmelot-van Hoek M, et al. Potency and selectivity of BTK Inhibitors in clinical development for B-cell malignancies. Blood. 2018;132(Supplement 1):1871. doi:10.1182/blood-2018-99-109973
   PubMed Web of Science ®Google Scholar
• Bye AP, Unsworth AJ, Desborough MJ, et al. Severe platelet dysfunction in NHL patients receiving ibrutinib is absent in patients receiving acalabrutinib. Blood Adv. 2017;1(26):2610–2623. doi:10.1182/bloodadvances.2017011999
   PubMed Web of Science ®Google Scholar
• Series J, Garcia C, Levade M, et al. Differences and similarities in the effects of ibrutinib and acalabrutinib on platelet functions. Haematologica. 2019;104(11):2292–2299. doi:10.3324/haematol.2018.207183
   PubMed Web of Science ®Google Scholar
• Patel V, Balakrishnan K, Bibikova E, et al. Comparison of acalabrutinib, A selective Bruton tyrosine kinase inhibitor, with ibrutinib in chronic lymphocytic leukemia cells. Clin Cancer Res. 2017;23(14):3734–3743. doi:10.1158/1078-0432.CCR-16-1446
   PubMed Web of Science ®Google Scholar
• Long M, Beckwith K, Do P, et al. Ibrutinib treatment improves T cell number and function in CLL patients. J Clin Invest. 2017;127(8):3052–3064. doi:10.1172/JCI89756
   PubMed Web of Science ®Google Scholar
• Kohrt HE, Sagiv-Barfi I, Rafiq S, et al. Ibrutinib antagonizes rituximab-dependent NK cell-mediated cytotoxicity. Blood. 2014;123(12):1957–1960. doi:10.1182/blood-2014-01-547869
   PubMed Web of Science ®Google Scholar
• 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(1):77–86. doi:10.3324/haematol.2014.107011
   PubMed Web of Science ®Google Scholar
• Borge M, Almejun MB, Podaza E, et al. Ibrutinib impairs the phagocytosis of rituximab-coated leukemic cells from chronic lymphocytic leukemia patients by human macrophages. Haematologica. 2015;100:e140–e142. doi:10.3324/haematol.2014.119669
   PubMed Web of Science ®Google Scholar
• Golay J, Ubiali G, Introna M. The specific Bruton tyrosine kinase inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B cells with CD20 antibodies. Haematologica. 2017;102(10):e400–e403. doi:10.3324/haematol.2017.169334
   PubMed Web of Science ®Google Scholar
• Patel VK, Lamothe B, Ayres ML, et al. Pharmacodynamics and proteomic analysis of acalabrutinib therapy: similarity of on-target effects to ibrutinib and rationale for combination therapy. Leukemia. 2018;32(4):920–930. doi:10.1038/leu.2017.321
   PubMed Web of Science ®Google Scholar
• Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42. doi:10.1056/NEJMoa1215637
   PubMed Web of Science ®Google Scholar
• Sun C, Nierman P, Kendall EK, et al. Clinical and biological implications of target occupancy in CLL treated with the BTK inhibitor acalabrutinib. Blood. 2020;136(1):93–105. doi:10.1182/blood.2019003715
   PubMed Web of Science ®Google Scholar
• Byrd JC, Wierda WG, Schuh A, et al. Acalabrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia: updated phase 2 results. Blood. 2020;135(15):1204–1213. doi:10.1182/blood.2018884940
   PubMed Web of Science ®Google Scholar
• Ghia P, Pluta A, Wach M, et al. ASCEND: phase III, randomized trial of acalabrutinib versus idelalisib plus rituximab or bendamustine plus rituximab in relapsed or refractory chronic lymphocytic leukemia. J Clin Oncol. 2020;38(25):2849–2861. doi:10.1200/JCO.19.03355
   PubMed Web of Science ®Google Scholar
• Byrd JC, Hillmen P, Ghia P, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39:3441–3452.
   PubMed Web of Science ®Google Scholar
• Burger JA, Sivina M, Jain N, et al. Randomized trial of ibrutinib vs ibrutinib plus rituximab in patients with chronic lymphocytic leukemia. Blood. 2019;133(10):1011–1019. doi:10.1182/blood-2018-10-879429
   PubMed Web of Science ®Google Scholar
• Woyach JA, Blachly JS, Rogers KA, et al. Acalabrutinib plus obinutuzumab in treatment-naïve and relapsed/refractory chronic lymphocytic leukemia. Cancer Discov. 2020;10(3):394–405. doi:10.1158/2159-8290.CD-19-1130
   PubMed Web of Science ®Google Scholar
• Byrd JC, Woyach JA, Furman RR, et al. Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Blood. 2021;137(24):3327–3338. doi:10.1182/blood.2020009617
   PubMed Web of Science ®Google Scholar
• Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278–1291. doi:10.1016/S0140-6736(20)30262-2
   PubMed Web of Science ®Google Scholar
• Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib ± obinutuzumab versus obinutuzumab + chlorambucil in treatment-naïve chronic lymphocytic leukemia: elevate-TN four-year follow up. J Clin Oncol. 2021;39(15_suppl):7509. doi:10.1200/JCO.2021.39.15_suppl.7509
   Web of Science ®Google Scholar
• Delgado J, Josephson F, Camarero J, et al. EMA review of acalabrutinib for the treatment of adult patients with chronic lymphocytic leukemia. Oncologist. 2021;26(3):242–249. doi:10.1002/onco.13685
   PubMed Web of Science ®Google Scholar
• Alrawashdh N, Persky DO, McBride A, Sweasy J, Erstad B, Abraham I. Comparative efficacy of first-line treatments of chronic lymphocytic leukemia: network meta-analyses of survival curves. Clin Lymphoma Myeloma Leuk. 2021;21(11):e820–e831. doi:10.1016/j.clml.2021.06.010
   PubMed Web of Science ®Google Scholar
• Awan FT, Schuh A, Brown JR, et al. Acalabrutinib monotherapy in patients with chronic lymphocytic leukemia who are intolerant to ibrutinib. Blood Adv. 2019;3(9):1553–1562. doi:10.1182/bloodadvances.2018030007
   PubMed Web of Science ®Google Scholar
• Rogers KA, Thompson PA, Allan JN, et al. Phase 2 study of acalabrutinib in ibrutinib (IBR)-intolerant patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL). J Clin Oncol. 2019;37(15_suppl):7530. doi:10.1200/JCO.2019.37.15_suppl.7530
   Web of Science ®Google Scholar
• Furman RR, Byrd JC, Owen RG, et al. Pooled analysis of safety data from clinical trials evaluating acalabrutinib monotherapy in mature B-cell malignancies. Leukemia. 2021;35:3201–3211. doi:10.1038/s41375-021-01252-y
   PubMed Web of Science ®Google Scholar
• Byrd JC, Furman RR, Coutre SE, et al. Ibrutinib treatment for first-line and relapsed/refractory chronic lymphocytic leukemia: final analysis of the pivotal phase Ib/II PCYC-1102 study. Clin Cancer Res. 2020;26(15):3918–3927. doi:10.1158/1078-0432.CCR-19-2856
   PubMed Web of Science ®Google Scholar
• Sheng Z, Song S, Yu M, et al. Comparison of acalabrutinib plus obinutuzumab, ibrutinib plus obinutuzumab and venetoclax plus obinutuzumab for untreated CLL: a network meta-analysis. Leuk Lymphoma. 2020;61(14):3432–3439. doi:10.1080/10428194.2020.1811271
   PubMed Web of Science ®Google Scholar
• Davids MS, Hallek M, Wierda W, et al. Comprehensive safety analysis of venetoclax monotherapy for patients with relapsed/refractory chronic lymphocytic leukemia. Clin Cancer Res. 2018;24(18):4371–4379. doi:10.1158/1078-0432.CCR-17-3761
   PubMed Web of Science ®Google Scholar
• Qiu Y, Kung HJ. Signaling network of the Btk family kinases. Oncogene. 2000;19(49):5651–5661. doi:10.1038/sj.onc.1203958
   PubMed Web of Science ®Google Scholar
• Pretorius L, Du XJ, Woodcock EA, et al. Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation. Am J Pathol. 2009;175(3):998–1009. doi:10.2353/ajpath.2009.090126
   PubMed Web of Science ®Google Scholar
• McMullen JR, Boey EJ, Ooi JY, Seymour JF, Keating MJ, Tam CS. Ibrutinib increases the risk of atrial fibrillation, potentially through inhibition of cardiac PI3K-Akt signaling. Blood. 2014;124(25):3829–3830. doi:10.1182/blood-2014-10-604272
   PubMed Web of Science ®Google Scholar
• Abbas HA, Wierda WG. Acalabrutinib: a selective Bruton tyrosine kinase inhibitor for the treatment of B-cell malignancies. Front Oncol. 2021;11:668162. doi:10.3389/fonc.2021.668162
   PubMed Web of Science ®Google Scholar
• Dickerson T, Wiczer T, Waller A, et al. Hypertension and incident cardiovascular events following ibrutinib initiation. Blood. 2019;134(22):1919–1928. doi:10.1182/blood.2019000840
   PubMed Web of Science ®Google Scholar
• Brown JR, Byrd JC, Ghia P, et al. Cardiovascular adverse events in patients with chronic lymphocytic leukemia receiving acalabrutinib monotherapy: pooled analysis of 762 patients. Haematologica. 2021. doi:10.3324/haematol.2021.278901
   Web of Science ®Google Scholar
• Byrd JC, Woyach JA, Furman RR, et al. Acalabrutinib in treatment-naïve chronic lymphocytic leukemia: mature results from phase II study demonstrating durable remissions and long-term tolerability. J Clin Oncol. 2020;38(15_suppl):8024. doi:10.1200/JCO.2020.38.15_suppl.8024
   Web of Science ®Google Scholar
• Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015;125(16):2497–2506. doi:10.1182/blood-2014-10-606038
   PubMed Web of Science ®Google Scholar
• Piercy KL, Troiano RP. Physical activity guidelines for Americans from the US department of health and human services. Circ Cardiovasc Qual Outcomes. 2018;11(11):e005263. doi:10.1161/CIRCOUTCOMES.118.005263
   PubMed Web of Science ®Google Scholar
• Lipsky A, Lamanna N. Managing toxicities of Bruton tyrosine kinase inhibitors. Hematology. 2020;2020(1):336–345. doi:10.1182/hematology.2020000118
   PubMed Web of Science ®Google Scholar
• Patel K, Sudhir VS, Kabadi S, et al. Impact of dosing frequency (once daily or twice daily) on patient adherence to oral targeted therapies for hematologic malignancies: a retrospective cohort study among managed care enrollees. J Oncol Pharm Pract. 2019;25(8):1897–1906. doi:10.1177/1078155219827637
   PubMed Web of Science ®Google Scholar
• Griggio V, Perutelli F, Salvetti C, et al. Immune dysfunctions and immune-based therapeutic interventions in chronic lymphocytic leukemia. Front Immunol. 2020;11:594556. doi:10.3389/fimmu.2020.594556
   PubMed Web of Science ®Google Scholar
• Vitale C, Boccellato E, Comba L, et al. Impact of immune parameters and immune dysfunctions on the prognosis of patients with chronic lymphocytic leukemia. Cancers. 2021;13(15):3856. doi:10.3390/cancers13153856
   PubMed Web of Science ®Google Scholar
• Fiorcari S, Maffei R, Vallerini D, et al. BTK inhibition impairs the innate response against fungal infection in patients with chronic lymphocytic leukemia. Front Immunol. 2020;11:2158. doi:10.3389/fimmu.2020.02158
   PubMed Web of Science ®Google Scholar
• Fiorcari S, Maffei R, Audrito V, et al. Ibrutinib modifies the function of monocyte/macrophage population in chronic lymphocytic leukemia. Oncotarget. 2016;7(40):65968–65981. doi:10.18632/oncotarget.11782
   PubMedGoogle Scholar
• Varughese T, Taur Y, Cohen N, et al. Serious infections in patients receiving ibrutinib for treatment of lymphoid cancer. Clin Infect Dis. 2018;67(5):687–692. doi:10.1093/cid/ciy175
   PubMed Web of Science ®Google Scholar
• Ahn IE, Jerussi T, Farooqui M, Tian X, Wiestner A, Gea-Banacloche J. Atypical pneumocystis jirovecii pneumonia in previously untreated patients with CLL on single-agent ibrutinib. Blood. 2016;128(15):1940–1943. doi:10.1182/blood-2016-06-722991
   PubMed Web of Science ®Google Scholar
• Facchinelli D, Marchesini G, Nadali G, Pagano L. Invasive fungal infections in patients with chronic lymphoproliferative disorders in the era of target drugs. Mediterr J Hematol Infect Dis. 2018;10(1):e2018063. doi:10.4084/mjhid.2018.063
   PubMedGoogle Scholar
• Mauro FR, Giannarelli D, Visentin A, et al. Prognostic impact and risk factors of infections in patients with chronic lymphocytic leukemia treated with ibrutinib. Cancers. 2021;13(13):3240. doi:10.3390/cancers13133240
   PubMed Web of Science ®Google Scholar
• Pleyer C, Sun C, Desai S, et al. Reconstitution of humoral immunity and decreased risk of infections in patients with chronic lymphocytic leukemia treated with Bruton tyrosine kinase inhibitors. Leuk Lymphoma. 2020;61(10):2375–2382. doi:10.1080/10428194.2020.1772477
   PubMed Web of Science ®Google Scholar
• 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(19):2213–2219. doi:10.1182/blood-2015-04-639203
   PubMed Web of Science ®Google Scholar
• Furman RR, Cheng S, Lu P, et al. Ibrutinib resistance in chronic lymphocytic leukemia. N Engl J Med. 2014;370(24):2352–2354. doi:10.1056/NEJMc1402716
   PubMed Web of Science ®Google Scholar
• Woyach JA, Ruppert AS, Guinn D, et al. BTK(C481S)-mediated resistance to ibrutinib in chronic lymphocytic leukemia. J Clin Oncol. 2017;35(13):1437–1443. doi:10.1200/JCO.2016.70.2282
   PubMed Web of Science ®Google Scholar
• Ahn IE, Underbayev C, Albitar A, et al. Clonal evolution leading to ibrutinib resistance in chronic lymphocytic leukemia. Blood. 2017;129(11):1469–1479. doi:10.1182/blood-2016-06-719294
   PubMed Web of Science ®Google Scholar