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CC BY 4.0 · Indian J Med Paediatr Oncol 2024; 45(02): 115-126
DOI: 10.1055/s-0044-1779621
DOI: 10.1055/s-0044-1779621
Review Article
FLT3 and IDH1/2 Inhibitors for Acute Myeloid Leukemia: Focused Clinical Narrative Review of Forthcoming Drugs from an Indian Context
1
Department of Clinical Hematology, Dayanand Medical College, Ludhiana, Punjab, India
,
Kunal Jain
2
Department of Medical Oncology, Dayanand Medical College, Ludhiana, Punjab, India
,
Jagdeep Singh
2
Department of Medical Oncology, Dayanand Medical College, Ludhiana, Punjab, India
,
Nitish Garg
2
Department of Medical Oncology, Dayanand Medical College, Ludhiana, Punjab, India
,
Akriti Arora
1
Department of Clinical Hematology, Dayanand Medical College, Ludhiana, Punjab, India
› Author Affiliations
Funding None declared.
Abstract
Therapeutic approaches for acute myeloid leukemia (AML) have witnessed minimal evolution in recent decades, primarily relying on advancements in supportive care and transplantation to drive improvements in overall survival rates. However, treatment with intensive chemotherapy may not be feasible for patients with advanced age or reduced fitness, and outcomes for patients with relapsed/refractory disease continue to be suboptimal. Several agents with a novel mechanism of action have been developed in the past decade and have shown efficacy in patients with both newly diagnosed and relapsed AML. Out of these, several FLT3 (FMS like tyrosine kinase 3) and IDH1/2 (isocitrate dehydrogenase 1/2) inhibitors have received regulatory approval in specific clinical settings and are available for clinical use. This is an actively expanding field with several ongoing clinical trials in advanced phases. We provide a focused narrative review of drugs from these two categories with available clinical data.
Patient Consent
None declared.
Publication History
Article published online:
09 February 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)
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References
- 1 Yates JW, Wallace Jr HJ, Ellison RR, Holland JF. Cytosine arabinoside (NSC-63878) and daunorubicin (NSC-83142) therapy in acute nonlymphocytic leukemia. Cancer Chemother Rep 1973; 57 (04) 485-488
- 2 Bertoli S, Tavitian S, Huynh A. et al. Improved outcome for AML patients over the years 2000-2014. Blood Cancer J 2017; 7 (12) 635
- 3 Shah A, Andersson TM, Rachet B, Björkholm M, Lambert PC. Survival and cure of acute myeloid leukaemia in England, 1971-2006: a population-based study. Br J Haematol 2013; 162 (04) 509-516
- 4 Khanal N, Shostrom V, Dhakal P. et al. Determinants of ten-year overall survival of acute myeloid leukemia: a large national cancer database analysis. Leuk Lymphoma 2022; 63 (04) 939-945
- 5 Singh S, Lionel S, Jain H. et al. Real world data on unique challenges and outcomes of older patients with AML from resource limited settings: Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC). Blood 2022; 140 (Suppl. 01) 6096-6098
- 6 Naur TMH, Jakobsen LH, Roug AS. et al. Treatment intensity and survival trends among real-world elderly AML patients diagnosed in the period 2001-2016: a Danish nationwide cohort study. Leuk Lymphoma 2021; 62 (08) 2014-2017
- 7 Medeiros BC. Is there a standard of care for relapsed AML?. Best Pract Res Clin Haematol 2018; 31 (04) 384-386
- 8 Löwenberg B, Huls G. The long road: improving outcome in elderly “unfit” AML?. Blood 2020; 135 (24) 2114-2115
- 9 Philip C, George B, Ganapule A. et al. Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol 2015; 170 (01) 110-117
- 10 Reitman ZJ, Yan H. Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J Natl Cancer Inst 2010; 102 (13) 932-941
- 11 Patel KP, Ravandi F, Ma D. et al. Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features. Am J Clin Pathol 2011; 135 (01) 35-45
- 12 Im AP, Sehgal AR, Carroll MP. et al. DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies. Leukemia 2014; 28 (09) 1774-1783
- 13 Ye D, Ma S, Xiong Y, Guan K-L. R-2-hydroxyglutarate as the key effector of IDH mutations promoting oncogenesis. Cancer Cell 2013; 23 (03) 274-276
- 14 Losman JA, Looper RE, Koivunen P. et al. (R)-2-hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible. Science 2013; 339 (6127) 1621-1625
- 15 Molenaar RJ, Thota S, Nagata Y. et al. Clinical and biological implications of ancestral and non-ancestral IDH1 and IDH2 mutations in myeloid neoplasms. Leukemia 2015; 29 (11) 2134-2142
- 16 Yen K, Travins J, Wang F. et al. AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations. Cancer Discov 2017; 7 (05) 478-493
- 17 Stein EM, DiNardo CD, Pollyea DA. et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017; 130 (06) 722-731
- 18 Fathi AT, DiNardo CD, Kline I. et al; AG221-C-001 Study Investigators. Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2: analysis of a phase 1/2 study. JAMA Oncol 2018; 4 (08) 1106-1110
- 19 Pollyea DA, Tallman MS, de Botton S. et al. Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia. Leukemia 2019; 33 (11) 2575-2584
- 20 DiNardo CD, Montesinos P, Schuh AC. et al. Outcomes for patients with late-stage mutant-IDH2 (m IDH2) relapsed/refractory acute myeloid leukemia (R/R AML) Treated with enasidenib vs other lower-intensity therapies in the randomized, phase 3 IDHentify trial. Blood 2021; 138 (Suppl. 01) 1243-1243
- 21 De Botton S, Risueño A, Schuh AC. et al. Overall survival by IDH2 mutant allele (R140 or R172) in patients with late-stage mutant-IDH2 relapsed or refractory acute myeloid leukemia treated with enasidenib or conventional care regimens in the phase 3 IDHENTIFY trial. J Clin Oncol 2022; 40 (16) 7005
- 22 Venugopal S, Takahashi K, Daver N. et al. Efficacy and safety of enasidenib and azacitidine combination in patients with IDH2 mutated acute myeloid leukemia and not eligible for intensive chemotherapy. Blood Cancer J 2022; 12 (01) 10
- 23 DiNardo CD, Schuh AC, Stein EM. et al. Enasidenib plus azacitidine versus azacitidine alone in patients with newly diagnosed, mutant-IDH2 acute myeloid leukaemia (AG221-AML-005): a single-arm, phase 1b and randomised, phase 2 trial. Lancet Oncol 2021; 22 (11) 1597-1608
- 24 Chan SM, Cameron C, Cathelin S. et al. Enasidenib in combination with venetoclax in IDH2-mutated myeloid malignancies: preliminary results of the phase Ib/II Enaven-AML trial. Blood 2021; 138 (Suppl. 01) 126
- 25 Popovici-Muller J, Lemieux RM, Artin E. et al. Discovery of AG-120 (ivosidenib): a first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers. ACS Med Chem Lett 2018; 9 (04) 300-305
- 26 DiNardo CD, Stein EM, de Botton S. et al. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med 2018; 378 (25) 2386-2398
- 27 Roboz GJ, DiNardo CD, Stein EM. et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood 2020; 135 (07) 463-471
- 28 DiNardo CD, Stein AS, Stein EM. et al. Mutant isocitrate dehydrogenase 1 inhibitor ivosidenib in combination with azacitidine for newly diagnosed acute myeloid leukemia. J Clin Oncol 2021; 39 (01) 57-65
- 29 Montesinos P, Recher C, Vives S. et al. Ivosidenib and azacitidine in IDH1-mutated acute myeloid leukemia. N Engl J Med 2022; 386 (16) 1519-1531
- 30 Stein EM, DiNardo CD, Fathi AT. et al. Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study. Blood 2021; 137 (13) 1792-1803
- 31 Merchant SL, Culos K, Wyatt H. Ivosidenib: IDH1 inhibitor for the treatment of acute myeloid leukemia. J Adv Pract Oncol 2019; 10 (05) 494-500
- 32 Jiang X, Wada R, Poland B. et al. Population pharmacokinetic and exposure-response analyses of ivosidenib in patients with IDH1-mutant advanced hematologic malignancies. Clin Transl Sci 2021; 14 (03) 942-953
- 33 DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood 2020; 135 (02) 85-96
- 34 Lachowiez CA, Borthakur G, Loghavi S. et al. Phase Ib/II study of the IDH1-mutant inhibitor ivosidenib with the BCL2 inhibitor venetoclax +/− azacitidine in IDH1-mutated hematologic malignancies. J Clin Oncol 2020; 38 (15) 7500-7500
- 35 Venugopal S, Watts J. Olutasidenib: from bench to bedside. Blood Adv 2023; 7 (16) 4358-4365
- 36 Watts J, Baer MR, Yang J. et al. Phase 1 study of the IDH1m inhibitor FT-2102 as a single agent in patients with IDH1m acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Blood 2018; 132: 1453
- 37 Watts JM, Baer MR, Yang J. et al. Olutasidenib (FT-2102), an IDH1m inhibitor as a single agent or in combination with azacitidine, induces deep clinical responses with mutation clearance in patients with acute myeloid leukemia treated in a phase 1 dose escalation and expansion study. Blood 2019; 134: 231
- 38 Watts JM, Baer MR, Yang J. et al. Olutasidenib alone or with azacitidine in IDH1-mutated acute myeloid leukaemia and myelodysplastic syndrome: phase 1 results of a phase 1/2 trial. Lancet Haematol 2023; 10 (01) e46-e58
- 39 de Botton S, Fenaux P, Yee K. et al. Olutasidenib (FT-2102) induces durable complete remissions in patients with relapsed or refractory IDH1-mutated AML. Blood Adv 2023; 7 (13) 3117-3127
- 40 Cortes JE, Esteve J, Bajel A. et al. Olutasidenib (FT-2102) in combination with azacitidine induces durable complete remissions in patients with mIDH1 acute myeloid leukemia. Blood 2021; 138: 698
- 41 Lyman SD, James L, Vanden Bos T. et al. Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. Cell 1993; 75 (06) 1157-1167
- 42 Gilliland DG, Griffin JD. The roles of FLT3 in hematopoiesis and leukemia. Blood 2002; 100 (05) 1532-1542
- 43 Friedman R. The molecular mechanisms behind activation of FLT3 in acute myeloid leukemia and resistance to therapy by selective inhibitors. Biochim Biophys Acta Rev Cancer 2022; 1877 (01) 188666
- 44 Shouval R, Shlush LI, Yehudai-Resheff S. et al. Single cell analysis exposes intratumor heterogeneity and suggests that FLT3-ITD is a late event in leukemogenesis. Exp Hematol 2014; 42 (06) 457-463
- 45 Schmid C, Labopin M, Socié G. et al; Acute Leukemia Working Party of the European Group of Blood and Bone Marrow Transplantation. Outcome of patients with distinct molecular genotypes and cytogenetically normal AML after allogeneic transplantation. Blood 2015; 126 (17) 2062-2069
- 46 Larrosa-Garcia M, Baer MR. FLT3 inhibitors in acute myeloid leukemia: current status and future directions. Mol Cancer Ther 2017; 16 (06) 991-1001
- 47 Zhang W, Konopleva M, Ruvolo VR. et al. Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway. Leukemia 2008; 22 (04) 808-818
- 48 Borthakur G, Kantarjian H, Ravandi F. et al. Phase I study of sorafenib in patients with refractory or relapsed acute leukemias. Haematologica 2011; 96 (01) 62-68
- 49 Levis M, Pham R, Smith BD, Small D. In vitro studies of a FLT3 inhibitor combined with chemotherapy: sequence of administration is important to achieve synergistic cytotoxic effects. Blood 2004; 104 (04) 1145-1150
- 50 Ravandi F, Cortes JE, Jones D. et al. Phase I/II study of combination therapy with sorafenib, idarubicin, and cytarabine in younger patients with acute myeloid leukemia. J Clin Oncol 2010; 28 (11) 1856-1862
- 51 Ravandi F, Arana Yi C, Cortes JE. et al. Final report of phase II study of sorafenib, cytarabine and idarubicin for initial therapy in younger patients with acute myeloid leukemia. Leukemia 2014; 28 (07) 1543-1545
- 52 Serve H, Krug U, Wagner R. et al. Sorafenib in combination with intensive chemotherapy in elderly patients with acute myeloid leukemia: results from a randomized, placebo-controlled trial. J Clin Oncol 2013; 31 (25) 3110-3118
- 53 Röllig C, Serve H, Hüttmann A. et al; Study Alliance Leukaemia. Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): a multicentre, phase 2, randomised controlled trial. Lancet Oncol 2015; 16 (16) 1691-1699
- 54 Röllig C, Serve H, Noppeney R. et al; Study Alliance Leukaemia (SAL). Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial. Leukemia 2021; 35 (09) 2517-2525
- 55 Stone RM, DeAngelo DJ, Klimek V. et al. Patients with acute myeloid leukemia and an activating mutation in FLT3 respond to a small-molecule FLT3 tyrosine kinase inhibitor, PKC412. Blood 2005; 105 (01) 54-60
- 56 Stone RM, Fischer T, Paquette R. et al. Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia. Leukemia 2012; 26 (09) 2061-2068
- 57 Stone RM, Mandrekar SJ, Sanford BL. et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 2017; 377 (05) 454-464
- 58 Keiffer G, Aderhold KL, Palmisiano ND. Upfront treatment of FLT3-mutated AML: a look back at the RATIFY trial and beyond. Front Oncol 2020; 10: 562219
- 59 Fischer T, Stone RM, Deangelo DJ. et al. Phase IIB trial of oral midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol 2010; 28 (28) 4339-4345
- 60 Dutreix C, Munarini F, Lorenzo S, Roesel J, Wang Y. Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers. Cancer Chemother Pharmacol 2013; 72 (06) 1223-1234
- 61 Ouatas T, Duval V, Sinclair K, Berkowitz N. Concomitant use of midostaurin with strong CYP3A4 inhibitors: an analysis from the Ratify trial. Blood 2017; 130: 381
- 62 Stemler J, Koehler P, Maurer C, Müller C, Cornely OA. Antifungal prophylaxis and novel drugs in acute myeloid leukemia: the midostaurin and posaconazole dilemma. Ann Hematol 2020; 99 (07) 1429-1440
- 63 Lam SSY, Leung AYH. Overcoming resistance to FLT3 inhibitors in the treatment of FLT3-mutated AML. Int J Mol Sci 2020; 21 (04) 1537
- 64 Zarrinkar PP, Gunawardane RN, Cramer MD. et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood 2009; 114 (14) 2984-2992
- 65 Cortes JE, Kantarjian H, Foran JM. et al. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol 2013; 31 (29) 3681-3687
- 66 Cortes J, Perl AE, Döhner H. et al. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol 2018; 19 (07) 889-903
- 67 Cortes JE, Khaled S, Martinelli G. et al. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol 2019; 20 (07) 984-997
- 68 Li J, Kankam M, Trone D, Gammon G. Effects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite. Br J Clin Pharmacol 2019; 85 (09) 2108-2117
- 69 Martínez-Cuadrón D, Rodríguez-Macías G, Rodríguez-Veiga R, Boluda B, Montesinos P. Practical considerations for treatment of relapsed/refractory FLT3-ITD acute myeloid leukaemia with quizartinib: illustrative case reports. Clin Drug Investig 2020; 40 (03) 227-235
- 70 Lee LY, Hernandez D, Rajkhowa T. et al. Preclinical studies of gilteritinib, a next-generation FLT3 inhibitor. Blood 2017; 129 (02) 257-260
- 71 Eguchi M, Minami Y, Kuzume A, Chi S. Mechanisms underlying resistance to FLT3 inhibitors in acute myeloid leukemia. Biomedicines 2020; 8 (08) 245
- 72 Perl AE, Altman JK, Cortes J. et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol 2017; 18 (08) 1061-1075
- 73 Perl AE, Altman JK, Cortes JE. et al. Final results of the chrysalis trial: a first-in-human phase 1/2 dose-escalation, dose-expansion study of gilteritinib (ASP2215) in patients with relapsed/refractory acute myeloid leukemia (R/R AML). Blood 2016; 128 (22) 1069
- 74 Perl AE, Martinelli G, Cortes JE. et al. Gilteritinib or chemotherapy for relapsed or refractory FLT3-mutated AML. N Engl J Med 2019; 381 (18) 1728-1740
- 75 Perl AE, Larson RA, Podoltsev NA. et al. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood 2022; 139 (23) 3366-3375
- 76 Smith CC, Levis MJ, Perl AE, Hill JE, Rosales M, Bahceci E. Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv 2022; 6 (07) 2144-2155
- 77 Wang ES, Montesinos P, Minden MD. et al. Phase 3 trial of gilteritinib plus azacitidine vs azacitidine for newly diagnosed FLT3mut+ AML ineligible for intensive chemotherapy. Blood 2022; 140 (17) 1845-1857
- 78 Nuhoğlu Kantarcı E, Eşkazan AE. Gilteritinib in the management of acute myeloid leukemia: current evidence and future directions. Leuk Res 2022; 114: 106808
- 79 Lewis NL, Lewis LD, Eder JP. et al. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers. J Clin Oncol 2009; 27 (31) 5262-5269
- 80 Zimmerman EI, Turner DC, Buaboonnam J. et al. Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia. Blood 2013; 122 (22) 3607-3615
- 81 Galanis A, Ma H, Rajkhowa T. et al. Crenolanib is a potent inhibitor of FLT3 with activity against resistance-conferring point mutants. Blood 2014; 123 (01) 94-100
- 82 Randhawa JK, Kantarjian HM, Borthakur G. et al. Results of a phase II study of crenolanib in relapsed/refractory acute myeloid leukemia patients (Pts) with activating FLT3 mutations. Blood 2014; 124 (21) 389
- 83 Aboudalle I, Kantarjian HM, Ohanian MN. et al. Phase I–II study of crenolanib combined with standard salvage chemotherapy and crenolanib combined with 5-azacitidine in acute myeloid leukemia patients with FLT3 activating mutations. Blood 2018; 132: 2715
- 84 Zhang H, Savage S, Schultz AR. et al. Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms. Nat Commun 2019; 10 (01) 244
- 85 Stone RM, Collins R, Tallman MS. et al. Effect of cytarabine/anthracycline/crenolanib induction on minimal residual disease (MRD) in newly diagnosed FLT3 mutant AML. J Clin Oncol 2017; 35 (15) 7016
- 86 Wang ES, Goldberg AD, Walter RB, Collins R, Stone RM. Long-term results of a phase 2 trial of crenolanib combined with 7+3 chemotherapy in adults with newly diagnosed FLT3 mutant AML. J Clin Oncol 2022; 40 (16) 7007
- 87 Choe S, Wang H, DiNardo CD. et al. Molecular mechanisms mediating relapse following ivosidenib monotherapy in IDH1-mutant relapsed or refractory AML. Blood Adv 2020; 4 (09) 1894-1905
- 88 Ward PS, Patel J, Wise DR. et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010; 17 (03) 225-234
- 89 Intlekofer AM, Shih AH, Wang B. et al. Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations. Nature 2018; 559 (7712) 125-129
- 90 Reinbold R, Hvinden IC, Rabe P. et al. Resistance to the isocitrate dehydrogenase 1 mutant inhibitor ivosidenib can be overcome by alternative dimer-interface binding inhibitors. Nat Commun 2022; 13 (01) 4785
- 91 Chang YT, Hernandez D, Alonso S. et al. Role of CYP3A4 in bone marrow microenvironment-mediated protection of FLT3/ITD AML from tyrosine kinase inhibitors. Blood Adv 2019; 3 (06) 908-916
- 92 Kumar B, Garcia M, Weng L. et al. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia 2018; 32 (03) 575-587
- 93 McMahon CM, Ferng T, Canaani J. et al. Clonal selection with RAS pathway activation mediates secondary clinical resistance to selective FLT3 inhibition in acute myeloid leukemia. Cancer Discov 2019; 9 (08) 1050-1063
- 94 Aikawa T, Togashi N, Iwanaga K. et al. Quizartinib, a selective FLT3 inhibitor, maintains antileukemic activity in preclinical models of RAS-mediated midostaurin-resistant acute myeloid leukemia cells. Oncotarget 2020; 11 (11) 943-955
- 95 McMahon CM, Canaani J, Rea B. et al. Mechanisms of acquired resistance to gilteritinib therapy in relapsed and refractory FLT3-mutated acute myeloid leukemia. Blood 2017; 130 (Suppl. 01) 29
- 96 Maschmeyer G, Bullinger L, Garcia-Vidal C. et al. Infectious complications of targeted drugs and biotherapies in acute leukemia. Clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL), a joint venture of the European Group for Blood and Marrow Transplantation (EBMT), the European Organization for Research and Treatment of Cancer (EORTC), the International Immunocompromised Host Society (ICHS) and the European Leukemia Net (ELN). Leukemia 2022; 36 (05) 1215-1226
- 97 Dombret H, Seymour JF, Butrym A. et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 2015; 126 (03) 291-299
- 98 DiNardo CD, Jonas BA, Pullarkat V. et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020; 383 (07) 617-629