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Recent Patents on Anti-Cancer Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-8928
ISSN (Online): 2212-3970

Mini-Review Article

Venetoclax in Acute Myeloid Leukemia

Author(s): Romeo G. Mihăilă*

Volume 18, Issue 1, 2023

Published on: 02 June, 2022

Page: [11 - 28] Pages: 18

DOI: 10.2174/1574892817666220429105338

Price: $65

Abstract

Background: Substantial progress in the therapeutic arsenal used to treat acute myeloid leukemia became possible in the last decade, as a result of advances in gene editing and descriptive and functional genomics.

Objective: The aim of this study is to analyze the efficacy and safety of venetoclax in the treatment of acute myeloid leukemia.

Methods: A mini-review was achieved using the articles published in PubMed and Web of Science in the last year, prior to 05.05.2021, which were searched using the terms “acute myeloid leukemia” and ”venetoclax” and the new patents published in this field.

Results: BCL-2 inhibitors administered in monotherapy are active against acute myeloid leukemia cells, but their efficacy is partially limited because they do not target other antiapoptotic proteins and venetoclax induced overexpression of the other antiapoptotic molecules. Venetoclax-based combinations (including those with hypomethylating agents) were able to improve outcomes for older patients with acute myeloid leukemia, including both remission rates and overall survival. Other drugs used in combination with venetoclax include: FLT3 inhibitors, IDH2 inhibitors, chidamide, ibrutinib, lapatinib, mivebresib, triptolide, metabolic inhibitors, nucleoside analogs, and classical chemotherapeutics. Both the mechanisms of venetoclax resistance and the ways to overcome it, as well as the adverse effects of venetoclax are analyzed.

Conclusion: The management of unfit and older patients with acute myeloid leukemia should be personalized and be the result of evaluating patient- and disease-specific factors that are essential to their care. Combinations that include venetoclax are an increasingly well-documented option for many of them.

Keywords: Acute myeloid leukemia, apoptosis, BCL-2, hypomethylating agent, minimal residual disease, myelodysplastic syn-drome, tumor lysis syndrome, venetoclax.

[1]
Chen EC, Garcia JS. Does patient fitness play a role in determining first-line treatment of acute myeloid leukemia? Hematology (Am Soc Hematol Educ Program) 2020; 2020(1): 41-50.
[http://dx.doi.org/10.1182/hematology.2020000087] [PMID: 33275683]
[2]
Swaminathan M, Wang ES. Novel therapies for AML: A round-up for clinicians. Expert Rev Clin Pharmacol 2020; 13(12): 1389-400.
[http://dx.doi.org/10.1080/17512433.2020.1850255] [PMID: 33412978]
[3]
Saxena K, Konopleva M. New treatment options for older patients with acute myeloid leukemia. Curr Treat Options Oncol 2021; 22(5): 39.
[http://dx.doi.org/10.1007/s11864-021-00841-4] [PMID: 33743079]
[4]
Kantarjian HM, Kadia TM, DiNardo CD, Welch MA, Ravandi F. Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. Cancer 2021; 127(8): 1186-207.
[http://dx.doi.org/10.1002/cncr.33477] [PMID: 33734442]
[5]
Kantarjian H, Kadia T, DiNardo C, et al. Acute myeloid leukemia: Current progress and future directions. Blood Cancer J 2021; 11(2): 41.
[http://dx.doi.org/10.1038/s41408-021-00425-3] [PMID: 33619261]
[6]
Perl AE. Which novel agents will have a clinically meaningful impact in AML at diagnosis? Best Pract Res Clin Haematol 2021; 34(1): 101257.
[http://dx.doi.org/10.1016/j.beha.2021.101257] [PMID: 33762111]
[7]
Fiorentini A, Capelli D, Saraceni F, Menotti D, Poloni A, Olivieri A. The time has come for targeted therapies for aml: Lights and shadows. Oncol Ther 2020; 8(1): 13-32.
[http://dx.doi.org/10.1007/s40487-019-00108-x] [PMID: 32700072]
[8]
Maiti A, DiNardo CD, Daver NG, et al. Triplet therapy with venetoclax, FLT3 inhibitor and decitabine for FLT3-mutated acute myeloid leukemia. Blood Cancer J 2021; 11(2): 25.
[http://dx.doi.org/10.1038/s41408-021-00410-w] [PMID: 33563904]
[9]
Daver N, Wei AH, Pollyea DA, Fathi AT, Vyas P, DiNardo CD. New directions for emerging therapies in acute myeloid leukemia: The next chapter. Blood Cancer J 2020; 10(10): 107.
[http://dx.doi.org/10.1038/s41408-020-00376-1] [PMID: 33127875]
[10]
Abdallah M, Xie Z, Ready A, Manogna D, Mendler JH, Loh KP. Management of acute myeloid leukemia (AML) in older patients. Curr Oncol Rep 2020; 22(10): 103.
[http://dx.doi.org/10.1007/s11912-020-00964-1] [PMID: 32725515]
[11]
Richardson DR, Green SD, Foster MC, Zeidner JF. Secondary AML emerging after therapy with hypomethylating agents: outcomes, prognostic factors, and treatment options. Curr Hematol Malig Rep 2021; 16(1): 97-111.
[http://dx.doi.org/10.1007/s11899-021-00608-6] [PMID: 33609248]
[12]
Lazarevic VL. Acute myeloid leukaemia in patients we judge as being older and/or unfit. J Intern Med 2021; 290(2): 279-93.
[http://dx.doi.org/10.1111/joim.13293] [PMID: 33780573]
[13]
Roberts AW. Therapeutic development and current uses of BCL-2 inhibition. Hematology (Am Soc Hematol Educ Program) 2020; 2020(1): 1-9.
[http://dx.doi.org/10.1182/hematology.2020000154] [PMID: 33275682]
[14]
Gangat N, Guglielmelli P, Szuber N, et al. Venetoclax with azacitidine or decitabine in blast-phase myeloproliferative neoplasm: A multicenter series of 32 consecutive cases. Am J Hematol 2021; 96(7): 781-9.
[http://dx.doi.org/10.1002/ajh.26186] [PMID: 33844862]
[15]
Rausch CR, DiNardo CD, Maiti A, et al. Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia. Cancer 2021; 127(14): 2489-99.
[http://dx.doi.org/10.1002/cncr.33508] [PMID: 33793970]
[16]
Ball S, Borthakur G. Apoptosis targeted therapies in acute myeloid leukemia: An update. Expert Rev Hematol 2020; 13(12): 1373-86.
[http://dx.doi.org/10.1080/17474086.2020.1852923] [PMID: 33205684]
[17]
Wei Y, Cao Y, Sun R, et al. Targeting Bcl-2 proteins in acute myeloid leukemia. Front Oncol 2020; 10: 584974.
[http://dx.doi.org/10.3389/fonc.2020.584974] [PMID: 33251145]
[18]
Thijssen R, Diepstraten ST, Moujalled D, et al. Intact TP-53 function is essential for sustaining durable responses to BH3-mimetic drugs in leukemias. Blood 2021; 137(20): 2721-35.
[http://dx.doi.org/10.1182/blood.2020010167] [PMID: 33824975]
[19]
Gurnari C, Pagliuca S, Visconte V. The interactome between metabolism and gene mutations in myeloid malignancies. Int J Mol Sci 2021; 22(6): 3135.
[http://dx.doi.org/10.3390/ijms22063135] [PMID: 33808599]
[20]
Emadi A, Kapadia B, Bollino D, et al. Venetoclax and pegcrisantaspase for complex karyotype acute myeloid leukemia. Leukemia 2021; 35(7): 1907-24.
[http://dx.doi.org/10.1038/s41375-020-01080-6] [PMID: 33199836]
[21]
Majumder MM, Leppä AM, Hellesøy M, et al. Multi-parametric single cell evaluation defines distinct drug responses in healthy hematologic cells that are retained in corresponding malignant cell types. Haematologica 2020; 105(6): 1527-38.
[http://dx.doi.org/10.3324/haematol.2019.217414] [PMID: 31439679]
[22]
Chua CC, Roberts AW, Reynolds J, et al. Chemotherapy and venetoclax in elderly acute myeloid leukemia trial (CAVEAT): A phase Ib dose-escalation study of venetoclax combined with modified intensive chemotherapy. J Clin Oncol 2020; 38(30): 3506-17.
[http://dx.doi.org/10.1200/JCO.20.00572] [PMID: 32687450]
[23]
Wang X, Mak PY, Mu H, et al. combinatorial inhibition of focal adhesion kinase and BCL-2 enhances antileukemia activity of venetoclax in acute myeloid leukemia. Mol Cancer Ther 2020; 19(8): 1636-48.
[http://dx.doi.org/10.1158/1535-7163.MCT-19-0841] [PMID: 32404407]
[24]
Buettner R, Nguyen LXT, Morales C, et al. Targeting the metabolic vulnerability of acute myeloid leukemia blasts with a combination of venetoclax and 8-chloro-adenosine. J Hematol Oncol 2021; 14(1): 70.
[http://dx.doi.org/10.1186/s13045-021-01076-4] [PMID: 33902674]
[25]
Nishi R, Shigemi H, Negoro E, Okura M, Hosono N, Yamauchi T. Venetoclax and alvocidib are both cytotoxic to acute myeloid leukemia cells resistant to cytarabine and clofarabine. BMC Cancer 2020; 20(1): 984.
[http://dx.doi.org/10.1186/s12885-020-07469-x] [PMID: 33046037]
[26]
Eide CA, Kurtz SE, Kaempf A, et al. Simultaneous kinase inhibition with ibrutinib and BCL2 inhibition with venetoclax offers a therapeutic strategy for acute myeloid leukemia. Leukemia 2020; 34(9): 2342-53.
[http://dx.doi.org/10.1038/s41375-020-0764-6] [PMID: 32094466]
[27]
Kam AYF, Piryani SO, Lee CL, et al. Selective ERBB2 and BCL2 Inhibition is synergistic for mitochondrial-mediated apoptosis in MDS and AML Cells. Mol Cancer Res 2021; 19(5): 886-99.
[http://dx.doi.org/10.1158/1541-7786.MCR-20-0973] [PMID: 33514658]
[28]
Shi YF, Liu L, He LL, et al. Combining triptolide with ABT-199 is effective against acute myeloid leukemia through reciprocal regulation of Bcl-2 family proteins and activation of the intrinsic apoptotic pathway. Cell Death Dis 2020; 11(7): 555.
[http://dx.doi.org/10.1038/s41419-020-02762-w] [PMID: 32699295]
[29]
Chen K, Yang Q, Zha J, et al. Preclinical evaluation of a regimen combining chidamide and ABT-199 in acute myeloid leukemia. Cell Death Dis 2020; 11(9): 778.
[http://dx.doi.org/10.1038/s41419-020-02972-2] [PMID: 32948748]
[30]
Singh Mali R, Zhang Q, DeFilippis RA, et al. Venetoclax combines synergistically with FLT3 inhibition to effectively target leukemic cells in FLT3-ITD+ acute myeloid leukemia models. Haematologica 2021; 106(4): 1034-46.
[http://dx.doi.org/10.3324/haematol.2019.244020] [PMID: 32414851]
[31]
Moses BS, McCullough S, Fox JM, et al. Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax. Blood Adv 2021; 5(3): 711-24.
[http://dx.doi.org/10.1182/bloodadvances.2020003429] [PMID: 33560385]
[32]
Grønningsæter IS, Reikvam H, Aasebø E, et al. Targeting cellular metabolism in acute myeloid leukemia and the role of patient heterogeneity. Cells 2020; 9(5): 1155.
[http://dx.doi.org/10.3390/cells9051155] [PMID: 32392896]
[33]
Upadhyay Banskota S, Khanal N, Bhatt VR. A precision medicine approach to management of acute myeloid leukemia in older adults. Curr Opin Oncol 2020; 32(6): 650-5.
[http://dx.doi.org/10.1097/CCO.0000000000000673] [PMID: 32826488]
[34]
Samra B, Konopleva M, Isidori A, Daver N, DiNardo C. Venetoclax-based combinations in acute myeloid leukemia: current evidence and future directions. Front Oncol 2020; 10: 562558.
[http://dx.doi.org/10.3389/fonc.2020.562558] [PMID: 33251134]
[35]
Bryant AL, LeBlanc TW, Albrecht T, et al. Oral adherence in adults with acute myeloid leukemia (AML): results of a mixed methods study. Support Care Cancer 2020; 28(11): 5157-64.
[http://dx.doi.org/10.1007/s00520-020-05349-5] [PMID: 32060702]
[36]
Wang L, Lin N. Double remission of chronic lymphocytic leukemia and secondary acute myeloid leukemia after venetoclax monotherapy: A case report. Medicine (Baltimore) 2021; 100(6): e24703.
[http://dx.doi.org/10.1097/MD.0000000000024703] [PMID: 33578607]
[37]
Bilbao-Sieyro C, Rodríguez-Medina C, Florido Y, et al. BCL2 Expression at post-induction and complete remission impact outcome in acute myeloid leukemia. Diagnostics (Basel) 2020; 10(12): 1048.
[http://dx.doi.org/10.3390/diagnostics10121048] [PMID: 33291851]
[38]
Pollyea DA. Venetoclax in AML: where we are and where we are headed. Clin Lymphoma Myeloma Leuk 2020; 20 (Suppl. 1): S25-6.
[http://dx.doi.org/10.1016/S2152-2650(20)30450-X] [PMID: 32862856]
[39]
Burnett A, Stone R. AML: New drugs but new challenges. Clin Lymphoma Myeloma Leuk 2020; 20(6): 341-50.
[http://dx.doi.org/10.1016/j.clml.2020.02.005] [PMID: 32151586]
[40]
Aldoss I, Pullarkat V, Stein AS. Venetoclax-containing regimens in acute myeloid leukemia. Ther Adv Hematol 2021; 12: 2040620720986646.
[http://dx.doi.org/10.1177/2040620720986646] [PMID: 33628408]
[41]
Azizi A, Ediriwickrema A, Dutta R, et al. Venetoclax and hypomethylating agent therapy in high risk myelodysplastic syndromes: a retrospective evaluation of a real-world experience. Leuk Lymphoma 2020; 61(11): 2700-7.
[http://dx.doi.org/10.1080/10428194.2020.1775214] [PMID: 32543932]
[42]
Agarwal S, Kowalski A, Schiffer M, Zhao J, Bewersdorf JP, Zeidan AM. Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: A step in the right direction or a game changer? Expert Rev Hematol 2021; 14(2): 199-210.
[http://dx.doi.org/10.1080/17474086.2021.1876559] [PMID: 33459064]
[43]
Gangat N, Tefferi A. Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: Literature survey and practice points. Blood Cancer J 2020; 10(11): 122.
[http://dx.doi.org/10.1038/s41408-020-00388-x] [PMID: 33230098]
[44]
Lachowiez C, DiNardo CD, Konopleva M. Venetoclax in acute myeloid leukemia - current and future directions. Leuk Lymphoma 2020; 61(6): 1313-22.
[http://dx.doi.org/10.1080/10428194.2020.1719098] [PMID: 32031033]
[45]
Apel A, Moshe Y, Ofran Y, et al. Venetoclax combinations induce high response rates in newly diagnosed acute myeloid leukemia patients ineligible for intensive chemotherapy in routine practice. Am J Hematol 2021; 96(7): 790-5.
[http://dx.doi.org/10.1002/ajh.26190] [PMID: 33836555]
[46]
Tenold ME, Moskoff BN, Benjamin DJ, et al. Outcomes of adults with relapsed/refractory acute myeloid leukemia treated with venetoclax plus hypomethylating agents at a comprehensive cancer center. Front Oncol 2021; 11: 649209.
[http://dx.doi.org/10.3389/fonc.2021.649209] [PMID: 33777810]
[47]
Feld J, Tremblay D, Dougherty M, et al. Safety and efficacy: clinical experience of venetoclax in combination with hypomethylating agents in both newly diagnosed and relapsed/refractory advanced myeloid malignancies. HemaSphere 2021; 5(4): e549.
[http://dx.doi.org/10.1097/HS9.0000000000000549] [PMID: 33718803]
[48]
Maiti A, Qiao W, Sasaki K, et al. Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment-related mortality. Am J Hematol 2021; 96(3): 282-91.
[http://dx.doi.org/10.1002/ajh.26061] [PMID: 33264443]
[49]
Schuler E, Wagner-Drouet EM, Ajib S, et al. Treatment of myeloid malignancies relapsing after allogeneic hematopoietic stem cell transplantation with venetoclax and hypomethylating agents-a retrospective multicenter analysis on behalf of the German Cooperative Transplant Study Group. Ann Hematol 2021; 100(4): 959-68.
[http://dx.doi.org/10.1007/s00277-020-04321-x] [PMID: 33191481]
[50]
Pollyea DA, Pratz K, Letai A, et al. Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study. Am J Hematol 2021; 96(2): 208-17.
[http://dx.doi.org/10.1002/ajh.26039] [PMID: 33119898]
[51]
DiNardo CD, Maiti A, Rausch CR, et al. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol 2020; 7(10): e724-36.
[http://dx.doi.org/10.1016/S2352-3026(20)30210-6] [PMID: 32896301]
[52]
Morsia E, McCullough K, Joshi M, et al. Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo Clinic series on 86 patients. Am J Hematol 2020; 95(12): 1511-21.
[http://dx.doi.org/10.1002/ajh.25978] [PMID: 32833294]
[53]
DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020; 383(7): 617-29.
[http://dx.doi.org/10.1056/NEJMoa2012971] [PMID: 32786187]
[54]
Aldoss I, Zhang J, Mei M, et al. Venetoclax and hypomethylating agents in FLT3-mutated acute myeloid leukemia. Am J Hematol 2020; 95(10): 1193-9.
[PMID: 32628327]
[55]
Ganzel C, Ram R, Gural A, et al. Venetoclax is safe and efficacious in relapsed/refractory AML. Leuk Lymphoma 2020; 61(9): 2221-5.
[http://dx.doi.org/10.1080/10428194.2020.1761964] [PMID: 32420775]
[56]
Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: A phase 3 randomized placebo-controlled trial. Blood 2020; 135(24): 2137-45.
[http://dx.doi.org/10.1182/blood.2020004856] [PMID: 32219442]
[57]
Feld J, Silverman LR, Navada SC. Forsaken pharmaceutical: Glasdegib in acute myeloid leukemia and myeloid diseases. Clin Lymphoma Myeloma Leuk 2021; 21(4): e415-22.
[http://dx.doi.org/10.1016/j.clml.2020.12.007] [PMID: 33547022]
[58]
Tremblay G, Daniele P, Bell T, Chan G, Brown A, Cappelleri JC. Comparative effectiveness of glasdegib versus venetoclax combined with low-dose cytarabine in acute myeloid leukemia. J Comp Eff Res 2021; 10(7): 603-12.
[http://dx.doi.org/10.2217/cer-2020-0280] [PMID: 33733815]
[59]
Koenig KL, Sahasrabudhe KD, Sigmund AM, Bhatnagar B. AML with myelodysplasia-related changes: Development, challenges, and treatment advances. Genes (Basel) 2020; 11(8): 845.
[http://dx.doi.org/10.3390/genes11080845] [PMID: 32722092]
[60]
Liu B, Guo Y, Deng L, Qiao Y, Jian J. The efficacy and adverse events of venetoclax in combination with hypomethylating agents treatment for patients with acute myeloid leukemia and myelodysplastic syndrome: A systematic review and meta-analysis. Hematology 2020; 25(1): 414-23.
[http://dx.doi.org/10.1080/16078454.2020.1843752] [PMID: 33191860]
[61]
Wilde L, Ramanathan S, Kasner M. B-cell lymphoma-2 inhibition and resistance in acute myeloid leukemia. World J Clin Oncol 2020; 11(8): 528-40.
[http://dx.doi.org/10.5306/wjco.v11.i8.528] [PMID: 32879842]
[62]
Zhang X, Qian J, Wang H, et al. Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia. Biomark Res 2021; 9(1): 30.
[http://dx.doi.org/10.1186/s40364-021-00288-7] [PMID: 33933163]
[63]
Short NJ, Montalban-Bravo G, Hwang H, et al. Prognostic and therapeutic impacts of mutant TP53 variant allelic frequency in newly diagnosed acute myeloid leukemia. Blood Adv 2020; 4(22): 5681-9.
[http://dx.doi.org/10.1182/bloodadvances.2020003120] [PMID: 33211826]
[64]
Patel KK, Zeidan AM, Shallis RM, Prebet T, Podoltsev N, Huntington SF. Cost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia. Blood Adv 2021; 5(4): 994-1002.
[http://dx.doi.org/10.1182/bloodadvances.2020003902] [PMID: 33591323]
[65]
Abbott D, Cherry E, Amaya M, et al. The propriety of upgrading responses to venetoclax + azacitidine in newly diagnosed patients with acute myeloid leukemia. Leuk Lymphoma 2021; 62(6): 1466-73.
[http://dx.doi.org/10.1080/10428194.2020.1864358] [PMID: 33375853]
[66]
Piccini M, Pilerci S, Merlini M, et al. Venetoclax-based regimens for relapsed/refractory acute myeloid leukemia in a real-life setting: A retrospective single-center experience. J Clin Med 2021; 10(8): 1684.
[http://dx.doi.org/10.3390/jcm10081684] [PMID: 33919958]
[67]
Thol F, Ganser A. Treatment of relapsed acute myeloid leukemia. Curr Treat Options Oncol 2020; 21(8): 66.
[http://dx.doi.org/10.1007/s11864-020-00765-5] [PMID: 32601974]
[68]
Byrne M, Danielson N, Sengsayadeth S, et al. The use of venetoclax-based salvage therapy for post-hematopoietic cell transplantation relapse of acute myeloid leukemia. Am J Hematol 2020; 95(9): 1006-14.
[http://dx.doi.org/10.1002/ajh.25859] [PMID: 32390196]
[69]
Amit O, On YB, Perez G, Shargian-Alon L, Yeshurun M, Ram R. Venetoclax and donor lymphocyte infusion for early relapsed acute myeloid leukemia after allogeneic hematopoietic cell transplantation. A retrospective multicenter trial. Ann Hematol 2021; 100(3): 817-24.
[http://dx.doi.org/10.1007/s00277-021-04398-y] [PMID: 33442793]
[70]
Lachowiez CA, Loghavi S, Furudate K, et al. Impact of splicing mutations in acute myeloid leukemia treated with hypomethylating agents combined with venetoclax. Blood Adv 2021; 5(8): 2173-83.
[http://dx.doi.org/10.1182/bloodadvances.2020004173] [PMID: 33885753]
[71]
Ramsey HE, Greenwood D, Zhang S, et al. BET inhibition enhances the antileukemic activity of low-dose venetoclax in acute myeloid leukemia. Clin Cancer Res 2021; 27(2): 598-607.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-1346] [PMID: 33148670]
[72]
Borthakur G, Odenike O, Aldoss I, et al. A phase 1 study of the pan-bromodomain and extraterminal inhibitor mivebresib (ABBV-075) alone or in combination with venetoclax in patients with relapsed/refractory acute myeloid leukemia. Cancer 2021; 127(16): 2943-53.
[http://dx.doi.org/10.1002/cncr.33590] [PMID: 33934351]
[73]
Zucenka A, Pileckyte R, Trociukas I, et al. Outcomes of relapsed or refractory acute myeloid leukemia patients failing venetoclax-based salvage therapies. Eur J Haematol 2021; 106(1): 105-13.
[http://dx.doi.org/10.1111/ejh.13527] [PMID: 32997830]
[74]
Jasra S, Kazemi M, Shah N, et al. Case report of combination therapy with azacytidine, enasidenib and venetoclax in primary refractory AML. Exp Hematol Oncol 2021; 10(1): 1.
[http://dx.doi.org/10.1186/s40164-020-00186-y] [PMID: 33397455]
[75]
Niu X, Rothe K, Chen M, et al. Targeting AXL kinase sensitizes leukemic stem and progenitor cells to venetoclax treatment in acute myeloid leukemia. Blood 2021; 137(26): 3641-55.
[http://dx.doi.org/10.1182/blood.2020007651] [PMID: 33786587]
[76]
Balachander SB, Criscione SW, Byth KF, et al. AZD4320, A Dual Inhibitor of Bcl-2 and Bcl-xL, induces tumor regression in hematologic cancer models without dose-limiting thrombocytopenia. Clin Cancer Res 2020; 26(24): 6535-49.
[http://dx.doi.org/10.1158/1078-0432.CCR-20-0863] [PMID: 32988967]
[77]
Haes I, Dendooven A, Mercier ML, et al. Absence of BCL-2 expression identifies a subgroup of AML with distinct phenotypic, molecular, and clinical characteristics. J Clin Med 2020; 9(10): 3090.
[http://dx.doi.org/10.3390/jcm9103090] [PMID: 32992732]
[78]
Kapoor I, Bodo J, Hill BT, Hsi ED, Almasan A. Targeting BCL-2 in B-cell malignancies and overcoming therapeutic resistance. Cell Death Dis 2020; 11(11): 941.
[http://dx.doi.org/10.1038/s41419-020-03144-y] [PMID: 33139702]
[79]
Zhang H, Nakauchi Y, Köhnke T, et al. Integrated analysis of patient samples identifies biomarkers for venetoclax efficacy and combination strategies in acute myeloid leukemia. Nat Can 2020; 1(8): 826-39.
[http://dx.doi.org/10.1038/s43018-020-0103-x] [PMID: 33123685]
[80]
Ruess DA, Heynen GJ, Ciecielski KJ, et al. Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase. Nat Med 2018; 24(7): 954-60.
[http://dx.doi.org/10.1038/s41591-018-0024-8] [PMID: 29808009]
[81]
Bhatt S, Pioso MS, Olesinski EA, et al. Reduced mitochondrial apoptotic priming drives resistance to BH3 mimetics in acute myeloid leukemia. Cancer Cell 2020; 38(6): 872-890.e6.
[http://dx.doi.org/10.1016/j.ccell.2020.10.010] [PMID: 33217342]
[82]
Stevens BM, Jones CL, Pollyea DA, et al. Fatty acid metabolism underlies venetoclax resistance in acute myeloid leukemia stem cells. Nat Can 2020; 1(12): 1176-87.
[http://dx.doi.org/10.1038/s43018-020-00126-z] [PMID: 33884374]
[83]
Jones CL, Stevens BM, Pollyea DA, et al. Nicotinamide metabolism mediates resistance to venetoclax in relapsed acute myeloid leukemia stem cells. Cell Stem Cell 2020; 27(5): 748-764.e4.
[http://dx.doi.org/10.1016/j.stem.2020.07.021] [PMID: 32822582]
[84]
Cojocari D, Smith BN, Purkal JJ, et al. Pevonedistat and azacitidine upregulate NOXA (PMAIP1) to increase sensitivity to venetoclax in preclinical models of acute myeloid leukemia. Haematologica 2021. Epub ahead of print
[PMID: 33853293]
[85]
Carter BZ, Mak PY, Tao W, et al. Targeting MCL-1 dysregulates cell metabolism and leukemia-stroma interactions and resensitizes acute myeloid leukemia to BCL-2 inhibition. Haematologica 2022; 107(1): 58-76.
[PMID: 33353284]
[86]
Garg R, Allen KJH, Dawicki W, Geoghegan EM, Ludwig DL, Dadachova E. 225Ac-labeled CD33-targeting antibody reverses resistance to Bcl-2 inhibitor venetoclax in acute myeloid leukemia models. Cancer Med 2021; 10(3): 1128-40.
[http://dx.doi.org/10.1002/cam4.3665] [PMID: 33347715]
[87]
Huang S, Li C, Zhang X, et al. Abivertinib synergistically strengthens the anti-leukemia activity of venetoclax in acute myeloid leukemia in a BTK-dependent manner. Mol Oncol 2020; 14(10): 2560-73.
[http://dx.doi.org/10.1002/1878-0261.12742] [PMID: 32519423]
[88]
Tambe M, Karjalainen E, Vähä-Koskela M, et al. Pan-RAF inhibition induces apoptosis in acute myeloid leukemia cells and synergizes with BCL2 inhibition. Leukemia 2020; 34(12): 3186-96.
[http://dx.doi.org/10.1038/s41375-020-0972-0] [PMID: 32651543]
[89]
Saliba AN, John AJ, Kaufmann SH. Resistance to venetoclax and hypomethylating agents in acute myeloid leukemia. Cancer Drug Resist 2021; 4: 125-42.
[PMID: 33796823]
[90]
Wang J, Ye X, Fan C, et al. Leukemia cutis with IDH1, DNMT3A and NRAS mutations conferring resistance to venetoclax plus 5-azacytidine in refractory AML. Biomark Res 2020; 8(1): 65.
[http://dx.doi.org/10.1186/s40364-020-00246-9] [PMID: 33292606]
[91]
Hormi M, Birsen R, Belhadj M, et al. Pairing MCL-1 inhibition with venetoclax improves therapeutic efficiency of BH3-mimetics in AML. Eur J Haematol 2020; 105(5): 588-96.
[http://dx.doi.org/10.1111/ejh.13492] [PMID: 32659848]
[92]
Masarova L, DiNardo CD, Bose P, et al. Single-center experience with venetoclax combinations in patients with newly diagnosed and relapsed AML evolving from MPNs. Blood Adv 2021; 5(8): 2156-64.
[http://dx.doi.org/10.1182/bloodadvances.2020003934] [PMID: 33885751]
[93]
Maiti A, DiNardo CD, Wang SA, et al. Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia. Blood Adv 2021; 5(7): 1876-83.
[http://dx.doi.org/10.1182/bloodadvances.2020003717] [PMID: 33792630]
[94]
Megías-Vericat JE, Solana-Altabella A, Ballesta-López O, Martínez-Cuadrón D, Montesinos P. Drug-drug interactions of newly approved small molecule inhibitors for acute myeloid leukemia. Ann Hematol 2020; 99(9): 1989-2007.
[http://dx.doi.org/10.1007/s00277-020-04186-0] [PMID: 32683457]
[95]
Bhatnagar S, Mukherjee D, Salem AH, Miles D, Menon RM, Gibbs JP. Dose adjustment of venetoclax when co-administered with posaconazole: Clinical drug-drug interaction predictions using a PBPK approach. Cancer Chemother Pharmacol 2021; 87(4): 465-74.
[http://dx.doi.org/10.1007/s00280-020-04179-w] [PMID: 33398386]
[96]
Venclyxto. Summary of product characteristics. Available from: https://www.ema.europa.eu (Accesed on: July 1, 2021).
[97]
Pelcovits A, Moore J, Bakow B, Niroula R, Egan P, Reagan JL. Tumor lysis syndrome risk in outpatient versus inpatient administration of venetoclax and hypomethlators for acute myeloid leukemia. Support Care Cancer 2021; 29(9): 5323-7.
[http://dx.doi.org/10.1007/s00520-021-06119-7] [PMID: 33661367]
[98]
Merchant M, Sampath D, Konopleva M, Han L. Combination of Bcl-2 inhibitor and MEK inhibitor for the treatment of cancer. Patent US 20180303815, 2018.
[99]
Ebersbach HE, Huber T, Jascur J, et al. Treatment of cancer using a CD33 chimeric antigen receptor. Patent US 20180044423, 2018.
[100]
Ciceri F, Lunardi S, Maes T, Mascaro Crusat C, Tirapu Fernandez De La Cuesta I. Combinations of LSD1 inhibitors for the treatment of hematological malignancies Patent US 20190083417, 2019.
[101]
Lauffer DJ, Bemis G, Boyd M, et al. Pteridinone compounds and uses thereof Patent US 20190322673, 2019.
[102]
Arthur W, Thurman R, Biechele T, Rohm R. Combinations of PBD-based antibody drug conjugates with Bcl-2 inhibitors. Patent US 20190076549, 2019.
[103]
Aktoudianakis E, Cho A, Du Z, et al. PD-1/PD-L1 inhibitors Patent US 20190345131, 2019.
[104]
Bayly A, Bleich M, Charrier JD, et al. GCN2 inhibitors and uses thereof Patent US 20190233425, 2019.
[105]
Greenwood JR, Masse CE. TYK2 inhibitors and uses thereof Patent US 20200172540, 2020.
[106]
Nehdi A, Boudjelal M, Alaskar A. Methods for treating cancer using purine analogs by depleting intracellular ATP Patent US 20200306285, 2020.
[107]
Shin Y, Cee VJ, Tegley CM, et al. KRAS G12C inhibitors and methods of using the same. Patent US 20200165231, 2020.
[108]
Estey EH. Acute myeloid leukemia: 2021 update on riskstratification and management. Am J Hematol 2020; 95(11): 1368-98.
[http://dx.doi.org/10.1002/ajh.25975] [PMID: 32833263]

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