Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3‐ITD: A multicenter phase 2 study

Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3‐internal tandem duplication (FLT3‐ITD) respond infrequently to salvage chemotherapy.

[1]  Yu Wang,et al.  Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial. , 2023, The Lancet. Haematology.

[2]  F. Mannelli,et al.  The Role of Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Past, Present, and Future Directions , 2023, Bioengineering.

[3]  Jie Xiao,et al.  Venetoclax Combined with Azacitidine and Homoharringtonine in Relapsed/Refractory AML: A Multicenter, Phase 2 Trial , 2023, Journal of Hematology & Oncology.

[4]  Jie Xiao,et al.  Genetic characteristics predict response to venetoclax plus hypomethylating agents in relapsed or refractory acute myeloid leukemia , 2022, Journal of internal medicine.

[5]  C. Bloomfield,et al.  Genomic landscape of patients with FLT3-mutated acute myeloid leukemia (AML) treated within the CALGB 10603/RATIFY trial , 2022, Leukemia.

[6]  N. Daver,et al.  Venetoclax Plus Gilteritinib for FLT3-Mutated Relapsed/Refractory Acute Myeloid Leukemia , 2022, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  A. Trumpp,et al.  Venetoclax synergizes with Gilteritinib in FLT3 wildtype high-risk Acute Myeloid Leukemia by suppressing MCL-1. , 2022, Blood.

[8]  B. Ebert,et al.  Diagnosis and Management of AML in Adults: 2022 ELN Recommendations from an International Expert Panel. , 2022, Blood.

[9]  G. Martinelli,et al.  Clinical outcomes in patients with relapsed/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib , 2022, Blood Cancer Journal.

[10]  M. Levis,et al.  Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib , 2022, Blood advances.

[11]  Ying Yang,et al.  The Basic Research of the Combinatorial Therapy of ABT-199 and Homoharringtonine on Acute Myeloid Leukemia , 2021, Frontiers in Oncology.

[12]  M. Konopleva,et al.  Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia , 2021, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  H. Einsele,et al.  Sorafenib or placebo in patients with newly diagnosed acute myeloid leukaemia: long-term follow-up of the randomized controlled SORAML trial , 2021, Leukemia.

[14]  Tamara J. Blätte,et al.  Clonal evolution of acute myeloid leukemia with FLT3-ITD mutation under treatment with midostaurin. , 2021, Blood.

[15]  M. Konopleva,et al.  Triplet therapy with venetoclax, FLT3 inhibitor and decitabine for FLT3-mutated acute myeloid leukemia , 2021, Blood Cancer Journal.

[16]  J. Byrd,et al.  Synergistic effect of BCL2 and FLT3 co-inhibition in acute myeloid leukemia , 2020, Journal of Hematology & Oncology.

[17]  S. Tu,et al.  Sorafenib maintenance in patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic haematopoietic stem-cell transplantation: an open-label, multicentre, randomised phase 3 trial. , 2020, The Lancet. Oncology.

[18]  K. Strauch,et al.  Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN). , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  M. Konopleva,et al.  Venetoclax combines synergistically with FLT3 inhibition to effectively target leukemic cells in FLT3-ITD+ acute myeloid leukemia models , 2020, Haematologica.

[20]  H. Kantarjian,et al.  Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia , 2020, Blood Cancer Journal.

[21]  C. Pui,et al.  Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: a phase 1, dose-escalation study. , 2020, The Lancet. Oncology.

[22]  M. Yao,et al.  Cytogenetics and mutations could predict outcome in relapsed and refractory acute myeloid leukemia patients receiving BCL-2 inhibitor venetoclax , 2020, Annals of Hematology.

[23]  E. Ma,et al.  Sorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms‐like tyrosine kinase 3 , 2020, Cancer.

[24]  M. Mohty,et al.  FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions , 2020, Leukemia.

[25]  C. Bloomfield,et al.  Impact of NPM1/FLT3-ITD genotypes defined by the2017 European LeukemiaNet in patients with acute myeloid leukemia. , 2019, Blood.

[26]  R. Larson,et al.  Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. , 2019, The New England journal of medicine.

[27]  G. Marcucci,et al.  Association of leukemia genetics with response to venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia , 2019, American journal of hematology.

[28]  Yu Wang,et al.  Sorafenib Therapy Is Associated with Improved Outcomes for FMS-like Tyrosine Kinase 3 Internal Tandem Duplication Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Stem Cell Transplantation. , 2019, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[29]  J. Taub,et al.  Inhibition of Bcl-2 Synergistically Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Preclinical Models of FLT3-Mutated Acute Myeloid Leukemia , 2019, Clinical Cancer Research.

[30]  H. Dombret,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. , 2019, The Lancet. Oncology.

[31]  Fei Liu,et al.  Outcomes of patients with relapsed or refractory acute myeloid leukemia: a population-based real-world study. , 2019, American journal of blood research.

[32]  Junmin Li,et al.  Homoharringtonine deregulates MYC transcriptional expression by directly binding NF-κB repressing factor , 2019, Proceedings of the National Academy of Sciences.

[33]  E. Estey,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. , 2018, The Lancet. Oncology.

[34]  Yu Wang,et al.  Effect of sorafenib on the outcomes of patients with FLT3‐ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation , 2018, Cancer.

[35]  M. Caligiuri,et al.  Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells , 2018, Nature Medicine.

[36]  W. Bolosky,et al.  Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid- and lymphoid-derived hematologic malignancies , 2017, Proceedings of the National Academy of Sciences.

[37]  C. Bloomfield,et al.  Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation , 2017, The New England journal of medicine.

[38]  R. Larson,et al.  Selective Inhibition of FLT3 by Gilteritinib in Relapsed/Refractory Acute Myeloid Leukemia: a Multicenter, First-in-human, Open-label, Phase 1/2 Study , 2017, The Lancet. Oncology.

[39]  M. Konopleva,et al.  Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments. , 2017, Clinical therapeutics.

[40]  Bob Löwenberg,et al.  Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. , 2017, Blood.

[41]  C. Craddock,et al.  Matched and mismatched unrelated donor compared to autologous stem cell transplantation for acute myeloid leukemia in first complete remission: a retrospective, propensity score-weighted analysis from the ALWP of the EBMT , 2016, Journal of Hematology & Oncology.

[42]  H. Einsele,et al.  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. , 2015, The Lancet. Oncology.

[43]  R. Kodet,et al.  Targeting of BCL2 Family Proteins with ABT-199 and Homoharringtonine Reveals BCL2- and MCL1-Dependent Subgroups of Diffuse Large B-Cell Lymphoma , 2015, Clinical Cancer Research.

[44]  S. Devine,et al.  Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study. , 2015, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[45]  S. Jane,et al.  Sorafenib priming may augment salvage chemotherapy in relapsed and refractory FLT3-ITD-positive acute myeloid leukemia , 2014, Blood Cancer Journal.

[46]  M. Konopleva,et al.  Treatment with FLT3 inhibitor in patients with FLT3‐mutated acute myeloid leukemia is associated with development of secondary FLT3–tyrosine kinase domain mutations , 2014, Cancer.

[47]  M. Levis.  FLT3 mutations in acute myeloid leukemia: what is the best approach in 2013? , 2013, Hematology. American Society of Hematology. Education Program.

[48]  Jiong Hu,et al.  Homoharringtonine-based induction regimens for patients with de-novo acute myeloid leukaemia: a multicentre, open-label, randomised, controlled phase 3 trial. , 2013, The Lancet. Oncology.

[49]  Z. Estrov,et al.  Salvage therapy using FLT3 inhibitors may improve long‐term outcome of relapsed or refractory AML in patients with FLT3‐ITD , 2013, British journal of haematology.

[50]  K. Götze,et al.  High activity of sorafenib in FLT3-ITD-positive acute myeloid leukemia synergizes with allo-immune effects to induce sustained responses , 2012, Leukemia.

[51]  S. Lok,et al.  Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation. , 2012, Blood.

[52]  M. Labopin,et al.  A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study , 2011, Leukemia.

[53]  M. Konopleva,et al.  Phase I study of sorafenib in patients with refractory or relapsed acute leukemias , 2011, Haematologica.

[54]  E. Estey,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. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  K. Döhner,et al.  Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure , 2017, Leukemia.