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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

Future Management of Chronic Myeloid Leukemia: From Dose Optimization to New Agents

Author(s): Massimo Breccia*, Emilia Scalzulli, Sara Pepe, Gioia Colafigli and Maurizio Martelli

Volume 22, Issue 10, 2022

Published on: 18 August, 2022

Page: [796 - 805] Pages: 10

DOI: 10.2174/1568009622666220613144253

Price: $65

Abstract

Background: The outcome of chronic myeloid leukemia (CML) patients in chronic phase has changed after the introduction of tyrosine kinase inhibitors (TKIs). The life expectancy is actually similar to that of the general population. Although outstanding results were achieved, about 20-30% of patients failed to achieve molecular milestones or experienced a severe toxicity and needed to switch to a second line.

Objective: The aim of this review is to report on possible future management in CML, from dose optimization to avoid long-term off-target events to new agents for the treatment of resistant and/or intolerant patients.

Methods: Broad research on Medline, Embase and archives from EHA and ASH congresses was performed.

Results: New TKIs have been developed to counteract resistance and/or intolerance in the setting of T315I mutated patients. The benefits of ponatinib dose optimization have been recently reported in the OPTIC trial. New trials to test the dose optimization are ongoing.

Conclusion: Reduction of the standard dose could be performed to reduce the specific TKI toxicity. Selective TKIs could be prescribed in the future as third line treatment.

Keywords: Chronic myeloid leukemia, resistance, intolerance, dose optimization, tyrosine kinase inhibitors, sequential treatment.

[1]
García-Gutiérrez, V.; Hernández-Boluda, J.C. Tyrosine kinase inhibitors available for chronic myeloid leukemia: Efficacy and safety. Front. Oncol., 2019, 9, 603.
[http://dx.doi.org/10.3389/fonc.2019.00603] [PMID: 31334123]
[2]
Bower, H.; Björkholm, M.; Dickman, P.W.; Höglund, M.; Lambert, P.C.; Andersson, T.M. Life expectancy of patients with chronic mye-loid leukemia approaches the life expectancy of the general population. J. Clin. Oncol., 2016, 34(24), 2851-2857.
[http://dx.doi.org/10.1200/JCO.2015.66.2866] [PMID: 27325849]
[3]
Hoffmann, V.S.; Baccarani, M.; Hasford, J.; Castagnetti, F.; Di Raimondo, F.; Casado, L.F.; Turkina, A.; Zackova, D.; Ossenkoppele, G.; Zaritskey, A.; Höglund, M.; Simonsson, B.; Indrak, K.; Sninska, Z.; Sacha, T.; Clark, R.; Bogdanovic, A.; Hellmann, A.; Griskevicius, L.; Schubert-Fritschle, G.; Sertic, D.; Guilhot, J.; Lejniece, S.; Zupan, I.; Burgstaller, S.; Koskenvesa, P.; Everaus, H.; Costeas, P.; Lindoerfer, D.; Rosti, G.; Saussele, S.; Hochhaus, A.; Hehlmann, R. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia, 2017, 31(3), 593-601.
[http://dx.doi.org/10.1038/leu.2016.246] [PMID: 27568522]
[4]
Cortes, J.E.; Saglio, G.; Kantarjian, H.M.; Baccarani, M.; Mayer, J.; Boqué, C.; Shah, N.P.; Chuah, C.; Casanova, L.; Bradley-Garelik, B.; Manos, G.; Hochhaus, A. Final 5-year study results of dasision: The dasatinib versus imatinib study in treatment-naïve chronic myeloid leukemia patients trial. J. Clin. Oncol., 2016, 34(20), 2333-2340.
[http://dx.doi.org/10.1200/JCO.2015.64.8899] [PMID: 27217448]
[5]
Hochhaus, A.; Saglio, G.; Hughes, T.P.; Larson, R.A.; Kim, D.W.; Issaragrisil, S.; le Coutre, P.D.; Etienne, G.; Dorlhiac-Llacer, P.E.; Clark, R.E.; Flinn, I.W.; Nakamae, H.; Donohue, B.; Deng, W.; Dalal, D.; Menssen, H.D.; Kantarjian, H.M. Long-term benefits and risks of front-line nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia, 2016, 30(5), 1044-1054.
[http://dx.doi.org/10.1038/leu.2016.5] [PMID: 26837842]
[6]
Cortes, J.E.; Gambacorti-Passerini, C.; Deininger, M.W.; Mauro, M.J.; Chuah, C.; Kim, D.W.; Dyagil, I.; Glushko, N.; Milojkovic, D.; le Coutre, P.; Garcia-Gutierrez, V.; Reilly, L.; Jeynes-Ellis, A.; Leip, E.; Bardy-Bouxin, N.; Hochhaus, A.; Brümmendorf, T.H. Bosutinib ver-sus imatinib for newly diagnosed chronic myeloid leukemia: Results from the randomized bfore trial. J. Clin. Oncol., 2018, 36(3), 231-237.
[http://dx.doi.org/10.1200/JCO.2017.74.7162] [PMID: 29091516]
[7]
Breccia, M.; Olimpieri, P.P.; Olimpieri, O.; Pane, F.; Iurlo, A.; Foggi, P.; Cirilli, A.; Colatrella, A.; Cuomo, M.; Gozzo, L.; Summa, V.; Cor-radini, P.; Russo, P. How many chronic myeloid leukemia patients who started a frontline second-generation tyrosine kinase inhibitor have to switch to a second-line treatment? A retrospective analysis from the monitoring registries of the italian medicines agency (AIFA). Cancer Med., 2020, 9(12), 4160-4165.
[http://dx.doi.org/10.1002/cam4.3071] [PMID: 32319737]
[8]
Kantarjian, H.M.; Giles, F.J.; Bhalla, K.N.; Pinilla-Ibarz, J.; Larson, R.A.; Gattermann, N.; Ottmann, O.G.; Hochhaus, A.; Radich, J.P.; Sa-glio, G.; Hughes, T.P.; Martinelli, G.; Kim, D.W.; Shou, Y.; Gallagher, N.J.; Blakesley, R.; Baccarani, M.; Cortes, J.; le Coutre, P.D. Ni-lotinib is effective in patients with chronic myeloid leukemia in chronic phase after imatinib resistance or intolerance: 24-month follow-up results. Blood, 2011, 117(4), 1141-1145.
[http://dx.doi.org/10.1182/blood-2010-03-277152] [PMID: 21098399]
[9]
Shah, N.P.; Guilhot, F.; Cortes, J.E.; Schiffer, C.A.; le Coutre, P.; Brümmendorf, T.H.; Kantarjian, H.M.; Hochhaus, A.; Rousselot, P.; Mohamed, H.; Healey, D.; Cunningham, M.; Saglio, G. Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: Follow-up of a phase 3 study. Blood, 2014, 123(15), 2317-2324.
[http://dx.doi.org/10.1182/blood-2013-10-532341] [PMID: 24569263]
[10]
Clark, R.E.; Polydoros, F.; Apperley, J.F.; Milojkovic, D.; Pocock, C.; Smith, G.; Byrne, J.L.; de Lavallade, H.; O’Brien, S.G.; Coffey, T.; Foroni, L.; Copland, M. De-escalation of tyrosine kinase inhibitor dose in patients with chronic myeloid leukaemia with stable major mo-lecular response (DESTINY): An interim analysis of a non-randomised, phase 2 trial. Lancet Haematol., 2017, 4(7), e310-e316.
[http://dx.doi.org/10.1016/S2352-3026(17)30066-2] [PMID: 28566209]
[11]
Clark, R.E.; Polydoros, F.; Apperley, J.F.; Milojkovic, D.; Rothwell, K.; Pocock, C.; Byrne, J.; de Lavallade, H.; Osborne, W.; Robinson, L.; O’Brien, S.G.; Read, L.; Foroni, L.; Copland, M. De-escalation of tyrosine kinase inhibitor therapy before complete treatment discon-tinuation in patients with chronic myeloid leukaemia (DESTINY): A non-randomised, phase 2 trial. Lancet Haematol., 2019, 6(7), e375-e383.
[http://dx.doi.org/10.1016/S2352-3026(19)30094-8] [PMID: 31201085]
[12]
Gottschalk, A.; Glauche, I.; Cicconi, S.; Clark, R.E.; Roeder, I. Molecular monitoring during dose reduction predicts recurrence after TKI cessation in CML. Blood, 2020, 135(10), 766-769.
[http://dx.doi.org/10.1182/blood.2019003395] [PMID: 31935278]
[13]
Cortes, E.J.; Apperley, J.; Lomaia, E.; Moiraghi, B.; Undurraga Sutton, M.; Pavlovsky, C.; Chuah, C.; Sacha, T.; Lipton, J.H.; Schiffer, C.; Deininger, M.W. OPTIC primary analysis: A dose-optimization study of 3 starting doses of ponatinib (PON). J. Clin. Oncol., 2021, 39, 7000.
[14]
Cortes, J.; Apperley, J.; Lomaia, E.; Moiraghi, B.; Undurraga Sutton, M.; Pavlovsky, C.; Chuah, C.; Sacha, T.; Lipton, J.H.; Schiffer, C.A.; McCloskey, J.; Hochhaus, A.; Rousselot, P.; Rosti, G.; de Lavallade, H.; Turkina, A.; Rojas, C.; Arthur, C.K.; Maness, L.; Talpaz, M.; Mauro, M.; Hall, T.; Lu, V.; Srivastava, S.; Deininger, M. Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: A randomized, open-label phase 2 clinical trial. Blood, 2021, 138(21), 2042-2050.
[http://dx.doi.org/10.1182/blood.2021012082] [PMID: 34407543]
[15]
Rea, D.; Cayuela, J.M.; Dulucq, S.; Etienne, G. Molecular responses after switching from a standard-dose twice-daily nilotinib regimen to a reduced-dose once-daily schedule in patients with chronic myeloid leukemia: A real life observational study (NILO-RED). Blood, 2017, 130(23), 318.
[16]
Breccia, M.; Abruzzese, E.; Stagno, F.; Iurlo, A.; Pane, F.; Attolico, I.; Sportoletti, P.; Pregno, P.; Galimberti, S.; Scappini, B.; Lemoli, R.M.; Siragusa, S.; Capodanno, I.; Chiodi, F.; Saglio, G.N.; Rosti, G. First intermin analysis of the italian dante study: De-esacaltion before treat-ment-free remission in patients with chronic myeloid leukemia treated with first-line nilotinib. Blood, 2021, 138(Suppl. 1), 1474.
[17]
Hughes, T.P.; Mauro, M.J.; Cortes, J.E.; Minami, H.; Rea, D.; DeAngelo, D.J.; Breccia, M.; Goh, Y.T.; Talpaz, M.; Hochhaus, A.; le Coutre, P.; Ottmann, O.; Heinrich, M.C.; Steegmann, J.L.; Deininger, M.W.N.; Janssen, J.J.W.M.; Mahon, F.X.; Minami, Y.; Yeung, D.; Ross, D.M.; Tallman, M.S.; Park, J.H.; Druker, B.J.; Hynds, D.; Duan, Y.; Meille, C.; Hourcade-Potelleret, F.; Vanasse, K.G.; Lang, F.; Kim, D.W. Asciminib in chronic myeloid leukemia after ABl kinase inhibitor failure. N. Engl. J. Med., 2019, 381(24), 2315-2326.
[http://dx.doi.org/10.1056/NEJMoa1902328] [PMID: 31826340]
[18]
Wylie, A.A.; Schoepfer, J.; Jahnke, W.; Cowan-Jacob, S.W.; Loo, A.; Furet, P.; Marzinzik, A.L.; Pelle, X.; Donovan, J.; Zhu, W.; Buonami-ci, S.; Hassan, A.Q.; Lombardo, F.; Iyer, V.; Palmer, M.; Berellini, G.; Dodd, S.; Thohan, S.; Bitter, H.; Branford, S.; Ross, D.M.; Hughes, T.P.; Petruzzelli, L.; Vanasse, K.G.; Warmuth, M.; Hofmann, F.; Keen, N.J.; Sellers, W.R. The allosteric inhibitor ABL001 enables dual targeting of BCR-ABL1. Nature, 2017, 543(7647), 733-737.
[http://dx.doi.org/10.1038/nature21702] [PMID: 28329763]
[19]
Mauro, M.J.; Kim, D.W.; Cortes, J.; Réa, D.; Hughes, T.P.; Minami, H.; Breccia, M.; DeAngelo, D.J.; Talpaz, M.; Hochhaus, A.; Goh, Y.T.; le Coutre, P.D.; Sondhi, M.; Mishra, K.; Hourcade-Potelleret, F.; Vanasse, G.; Aimone, P.; Lang, F. Combination of asciminib plus ni-lotinib (NIL) or dasatinib (DAS) in patients (pts) with chronic myeloid leukemia (CML): Results from a phase 1 study. EHA, 2019, 2019, S884.
[20]
Cortes, J.; Lang, F.; Kim, D.W.; Réa, D.; Mauro, M.J.; Minami, H.; Breccia, M.; DeAngelo, D.J.; Talpaz, M.; Hochhaus, A.; Goh, Y.T.; le Coutre, P.D.; Sondhi, M.; Mishra, K.; Hourcade-Potelleret, F.; Vanasse, G.; Aimone, P.; Hughes, T.P. Combination therapy using ascimin-ib plus imatinib (ima) in patients with chronic myeloid leukemia (CML): Results from a phase 1 study. EHA, 2019, 2019, S883.
[21]
Cortes, J.; Hughes, T.P.; Mauro, M.J.; Hochhaus, A.; Réa, D.; Goh, Y.T.; Janssen, J.; Steegmann, J.L.; Heinrich, M.C.; Talpaz, M.; Etienne, G.; Breccia, M.; Deininger, M.W.; le Coutre, P.D.; Lang, F.; Aimone, P.; Polydoros, F.; Cacciatore, S.; Stenson, L.; Kim, D.W. Asciminib, a First-in-Class STAMP Inhibitor, provides durable molecular response in patients (pts) with chronic myeloid leukemia (CML) harboring the T315I mutation: Primary efficacy and safety results from a phase 1 trial. Blood, 2020, 136(Suppl. 1), 47-50.
[http://dx.doi.org/10.1182/blood-2020-139677]
[22]
Hochhaus, A.; Boquimpani, C.; Rea, D.; Minami, Y.; Lomaia, E.; Voloshin, S.; Turkina, A.G.; Kim, D.W.; Apperley, J.; Cortes, J.E.; Abdo, A.; Fogliatto, L.M.; Kim, D.D.H.; le Coutre, P.D.; Saussele, S.; Annunziata, M.; Hughes, T.P.; Chaudhri, N.A.; Chee, L.C.Y.; Gutièrrez, V.G.; Sasaki, K.; Aimone, P.; Allepuz, A.; Quenet, S.; Bèdoucha, V.; Mauro, M.J. Efficacy and safety results from ASCEMBL, a multicen-ter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs. bosutinib in patients with chronic myeloid leukemia in chronic phase previously treated with > 2 tyrosine kinase inhibitors. Blood, 2020, 136(s1)(Suppl. 2)LBA–4
[http://dx.doi.org/10.1182/blood-2020-143816]
[23]
Réa, D.; Mauro, M.J.; Boquimpani, C.; Minami, Y.; Lomaia, E.; Voloshin, S.; Turkina, A.; Kim, D.W.; Apperley, J.F.; Abdo, A.; Fogliatto, L.M.; Kim, D.D.H.; le Coutre, P.; Saussele, S.; Annunziata, M.; Hughes, T.P.; Chaudhri, N.; Sasaki, K.; Chee, L.; García-Gutiérrez, V.; Cortes, J.E.; Aimone, P.; Allepuz, A.; Quenet, S.; Bédoucha, V.; Hochhaus, A. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs. bosutinib in CML after 2 or more prior TKIs. Blood, 2021, 138(21), 2031-2041.
[http://dx.doi.org/10.1182/blood.2020009984] [PMID: 34407542]
[24]
Antelope, O.; Vellore, N.A.; Pomicter, A.D.; Patel, A.B.; Van Scoyk, A.; Clair, P.M.; Deininger, M.W.; O’Hare, T. BCR-ABL1 tyrosine kinase inhibitor K0706 exhibits preclinical activity in Philadelphia chromosome-positive leukemia. Exp. Hematol., 2019, 77, 36-40.e2.
[http://dx.doi.org/10.1016/j.exphem.2019.08.007] [PMID: 31493432]
[25]
Cortes, J.E.; Kim, D.W.; Nicolini, F.E.; Saikia, T.; Charbonnier, A.; Apperley, J.F.; Rathnam, K.; Deininger, M.W.; De Lavallade, H.; Khattry, N.; Whiteley, A.; Mauro, M.J.; Verhoef, G.; Gambacorti-Passerini, C.; Lucchesi, A.; Apte, S.; Nikki, G.; Yao, S.L.; Kothekar, M.; Sreenivasan, J.; Bimba, H.V.; Chimote, G. Phase 1 Trial of K0706, a novel oral BCR-ABL1 Tyrosine Kinase Inhibitor (TKI): In patients with chronic myelogenous leukemia (CML) and phildelphia positive acute lymphoblastic leukemia (Ph+ ALL) failing ≥ 3 prior TKI thera-pies: Initial safety and efficacy. Blood, 2019, 134(Suppl. 1), 4158.
[http://dx.doi.org/10.1182/blood-2019-129751]
[26]
Cortes, J.E.; Saikia, T.; Kim, D.W.; Alvarado, Y.; Nicolini, F.E.; Khattry, N.; Rathnam, K.; Apperley, J.; Deininger, M.W.; de Lavallade, H.; Charbonnier, A.; Granacher, N.; Gambacordi-Passarini, C.; Lucchesi, A.; Mauro, M.J.; Verhoef, G.; Vandenberghe, P.; Whiteley, A.R.; Apte, S.; Yao, S.L.; Kothekar, M.; Sreenivasan, J.; Bimba, H.V.; Chimote, G. Phase 1 trial of vodobatinib, a novel oral BCR-ABL1 tyrosine kinase inhibitor (TKI): Activity in CML chronic phase patients failing TKI therapies including ponatinib. Blood, 2020, 136(Suppl. 1), 51-52.
[http://dx.doi.org/10.1182/blood-2020-139847]
[27]
Cortes, J.E.; Saikia, T.; Kim, D.W.; Alvarado, Y.; Nicolini, F.E.; Rathnam, K.; Khattry, N.; Apperley, J.; Deininger, M.W.; de Lavallade, H.; Charbonnier, A.; Granacher, N.; Gambacordi-Passarini, C.; Lucchesi, A.; Mauro, M.J.; Vandenberghe, P.; Verhoef, G.; Whiteley, A.R.; Nag, A.; Radhakrishnan, V.S.; Apte, S.; Yao, S.L.; Inamdar, S.; Sreenivasan, J.; Dillu, R.I.; Chimote, G. An update of safety and efficacy results from Phase 1 Dose- Escalation and Expansion Study of Vodobatinib, a novel oral BCRABL1 Tyrosine Kinase Inhibitor (TKI), in patients with Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL) failing prior TKI therapies. Blood, 2021, 138(supplement 2), abstract 309.
[28]
Ren, X.; Pan, X.; Zhang, Z.; Wang, D.; Lu, X.; Li, Y.; Wen, D.; Long, H.; Luo, J.; Feng, Y.; Zhuang, X.; Zhang, F.; Liu, J.; Leng, F.; Lang, X.; Bai, Y.; She, M.; Tu, Z.; Pan, J.; Ding, K. Identification of GZD824 as an orally bioavailable inhibitor that targets phosphorylated and nonphosphorylated breakpoint cluster region-Abelson (Bcr-Abl) kinase and overcomes clinically acquired mutation-induced resistance against imatinib. J. Med. Chem., 2013, 56(3), 879-894.
[http://dx.doi.org/10.1021/jm301581y] [PMID: 23301703]
[29]
Jiang, Q.; Huang, X.; Chen, Z.; Niu, Q.; Men, L.; Wang, H.; Jl, J.; Huang, B.; Shi, D.; Zhao, T.; Hou, Y.; Yang, D.; Zhai, Y. An updated safety and efficacy results of Phase 1 Study of HQP1351, a novel 3rd generation of BCR-ABL Tyrosine Kinase Inhibitor (TKI), in pa-tients with TKI resistant Chronic Myeloid Leukemia. Blood, 2019, 134(Suppl. 1), 493.
[http://dx.doi.org/10.1182/blood-2019-124295]
[30]
Jiang, Q.; Shi, D.; Li, Z.; Qin, Y.; Zhao, T.; Liu, B.; Chen, Z.; Niu, Q.; Men, L.; Wang, H.; Yang, D.; Zhai, Y.; Huang, X. Updated safety and efficacy results of Phase 1 Study of Olverembatinib (HQP1351), a novel Third-Generation BCR-ABL Tyrosine Kinase Inhibitor (TKI), in patients with TKI-resistant Chronic Myeloid Leukemia (CML). Blood, 2021, 138(Suppl. 2), 311.
[31]
Jiang, Q.; Huang, X.; Chen, Z.; Niu, Q.; Shi, D.; Li, Z.; Hou, Y.; Hu, Y.; Li, W.; Liu, X.; Xu, N.; Song, Y.; Zhang, Y.; Meng, L.; Hong, Z.; Liu, B.; Zeng, S.; Men, L.; Li, Y.; Chen, S.; Xue, M.; Zhu, H.; Li, H.; Du, X.; Lou, J.; Zhang, X.; Liang, Y.; Dai, Y.; Lu, M.; Wang, H.; Jl, J.; Yue, C.; Yang, D.; Zhai, Y. Novel BCR-ABL1 tyrosine kinase inhibitor (TKI) HQP1351 (olverembatinib) is efficacious and well toler-ated in patients with T315I-mutated chronic myeloid leukemia (CML): Results of pivotal (phase II) trials. Blood, 2020, 136(Suppl. 1), 50-51.
[http://dx.doi.org/10.1182/blood-2020-142142]
[32]
Jiang, Q.; Shi, D.; Li, Z.; Hou, Y.; Hu, Y.; Li, W.; Liu, X.; Song, Y.; Zhang, G.; Meng, L.; Hong, Z.; Liu, B.; Li, Y.; Chen, S.; Xue, M.; Zhu, H.; Li, H.; Du, X.; Lou, J.; Zhang, X.; Liang, Y.; Dai, Y.; Chen, Z.; Niu, Q.; Men, L.; Yang, D.; Zhai, Y.; Huang, X. Updated results of piv-otal Phase 2 Trials of Olverembatinib (HQP1351) in patients (Pts) with Tyrosine Kinase Inhibitor (TKI)-Resistant BCR-ABL1T315I-Mutated Chronic- and Accelerated-Phase Chronic Myeloid Leukemia (CML-CP and CML-AP). Blood, 2021, 138(Suppl. 2), 3598.
[33]
Ivanova, E.S.; Tatarskiy, V.V.; Yastrebova, M.A.; Khamidullina, A.I.; Shunaev, A.V.; Kalinina, A.A.; Zeifman, A.A.; Novikov, F.N.; Du-tikova, Y.V.; Chilov, G.G.; Shtil, A.A. PF 114, a novel selective inhibitor of BCR ABL tyrosine kinase, is a potent inducer of apoptosis in chronic myelogenous leukemia cells. Int. J. Oncol., 2019, 55(1), 289-297.
[http://dx.doi.org/10.3892/ijo.2019.4801] [PMID: 31115499]
[34]
Mian, A.A.; Rafiei, A.; Haberbosch, I.; Zeifman, A.; Titov, I.; Stroylov, V.; Metodieva, A.; Stroganov, O.; Novikov, F.; Brill, B.; Chilov, G.; Hoelzer, D.; Ottmann, O.G.; Ruthardt, M. PF-114, a potent and selective inhibitor of native and mutated BCR/ABL is active against Philadelphia chromosome-positive (Ph+) leukemias harboring the T315I mutation. Leukemia, 2015, 29(5), 1104-1114.
[http://dx.doi.org/10.1038/leu.2014.326] [PMID: 25394714]
[35]
Turkina, A.G.; Vinogradova, O.; Lomaia, E.; Shatokhina, E.; Shukhov, O.A.; Chelysheva, E.Y.; Shikhbabaeba, D.; Nemchenko, I.; Pe-trova, A.; Bykova, A.; Zaritskey, A.; Siordia, N.; Shuvaev, V.; Cortes, J.E.; Peter Gale, R.; Baccarini, M.; Ottmann, O.; Mikhailov, I.; Novikov, F.; Shulgina, V.; Chilov, G. PF-114: A 4th generation tyrosine kinase-inhibitor for chronic phase chronic myeloid leukaemia in-cluding BCRABL1T315I. Blood, 2019, 134(Suppl. 1), 1638.
[http://dx.doi.org/10.1182/blood-2019-127951]
[36]
Turkina, A.G.; Vinogradova, O.; Lomaia, E.; Shatokhina, E.; Shukhov, O.A.; Zaritskey, A.; Chelysheva, E.Y.; Shikhbabaeba, D.; Nem-chenko, I.; Petrova, A.; Bykova, A.; Shuvaev, V.; Siordia, N.; Cortes, J.E.; Peter Gale, R.; Baccarini, M.; Ottmann, O.; Mikhailov, I.; Novikov, F.; Shulgina, V.; Chilov, G. PF-114 in patients failing prior Tyrosine Kinase-Inhibitor therapy including BCR:ABL1T315I. Blood, 2021, 138(Suppl. 2), 1482.
[37]
Levine, A.J.; Oren, M. The first 30 years of p53: Growing ever more complex. Nat. Rev. Cancer, 2009, 9(10), 749-758.
[http://dx.doi.org/10.1038/nrc2723] [PMID: 19776744]
[38]
Saiki, A.Y.; Caenepeel, S.; Yu, D.; Lofgren, J.A.; Osgood, T.; Robertson, R.; Canon, J.; Su, C.; Jones, A.; Zhao, X.; Deshpande, C.; Payton, M.; Ledell, J.; Hughes, P.E.; Oliner, J.D. MDM2 antagonists synergize broadly and robustly with compounds targeting fundamental onco-genic signaling pathways. Oncotarget, 2014, 5(8), 2030-2043.
[http://dx.doi.org/10.18632/oncotarget.1918] [PMID: 24810962]
[39]
Taylor, A.; Lee, D.; Allard, M.; Poland, B.; Greg Slatter, J. Phase 1 Concentration-QTc and cardiac safety analysis of the MDM2 Antago-nist KRT-232 in patients with advanced solid tumors, Multiple Myeloma, or Acute Myeloid Leukemia. Clin. Pharmacol. Drug Dev., 2021, 10(8), 918-926.
[http://dx.doi.org/10.1002/cpdd.903] [PMID: 33460527]
[40]
Templeton, I.E.; Podoll, T.; Krejsa, C.M.; Slatter, J.G. A mechanistic physiologically based pharmacokinetic (PBPK) drug interaction mod-el for the mouse double minute 2 (MDM2) inhibitor KRT-232. Blood, 2020, 136(Suppl. 1), 9-10.
[http://dx.doi.org/10.1182/blood-2020-135987]
[41]
Malik, S.; Hassan, S.; Eşkazan, A.E. Novel BCR-ABL1 tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia. Expert Rev. Hematol., 2021, 14(11), 975-978.
[http://dx.doi.org/10.1080/17474086.2021.1990034] [PMID: 34608829]

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