ENABLE: treatment combination including decitabine and venetoclax in acute myeloid leukemia secondary to myeloproliferative neoplasms.

The management of patients with acute myeloid leukemia (blast phase) secondary to myeloproliferative neoplasms (MPNs) is extremely challenging and the outcome dismal, with a median overall survival of about 3-6 months. Effective therapeutic approaches are lacking, especially when intensive strategies followed by allogeneic transplantation are not feasible. The combination of venetoclax and hypomethylating agents has recently been established as standard for newly diagnosed, unfit patients with de novo acute myeloid leukemia, but the application of this therapeutic modality has not been tested prospectively in the specific context of blast-phase MPNs. ENABLE is an open, phase II clinical trial aimed at verifying the efficacy and safety of the combination of venetoclax and decitabine in patients with post-MPN blast phase.

[1]  M. Konopleva,et al.  Single-center experience with venetoclax combinations in patients with newly diagnosed and relapsed AML evolving from MPNs. , 2021, Blood advances.

[2]  P. Guglielmelli,et al.  Venetoclax with azacitidine or decitabine in blast‐phase myeloproliferative neoplasm: A multicenter series of 32 consecutive cases , 2021, American journal of hematology.

[3]  A. Shih,et al.  Venetoclax and hypomethylating agent combination therapy in acute myeloid leukemia secondary to a myeloproliferative neoplasm. , 2020, Leukemia research.

[4]  A. Tefferi,et al.  Venetoclax plus hypomethylating agent in blast‐phase myeloproliferative neoplasm: preliminary experience with 12 patients , 2020, British journal of haematology.

[5]  J. Novak,et al.  Venetoclax plus LDAC for patients with untreated AML ineligible for intensive chemotherapy: phase 3 randomized placebo-controlled trial. , 2020, Blood.

[6]  D. Pollyea,et al.  How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia , 2019, Leukemia.

[7]  A. Letai,et al.  Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. , 2019, Blood.

[8]  A. Letai,et al.  Venetoclax in Combination with Hypomethylating Agents Induces Rapid, Deep, and Durable Responses in Patients with AML Ineligible for Intensive Therapy , 2018, Blood.

[9]  G. Marcucci,et al.  Efficacy of the combination of venetoclax and hypomethylating agents in relapsed/refractory acute myeloid leukemia , 2018, Haematologica.

[10]  M. Konopleva,et al.  Clinical experience with the BCL2‐inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies , 2018, American journal of hematology.

[11]  P. Guglielmelli,et al.  Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from two separate cohorts , 2018, Leukemia.

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

[13]  M. Kurokawa,et al.  Allogeneic Hematopoietic Cell Transplantation for Leukemic Transformation Preceded by Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Nationwide Survey by the Adult Acute Myeloid Leukemia Working Group of the Japan Society for Hematopoietic Cell Transplantation. , 2016, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[14]  J. Mascarenhas.  A Concise Update on Risk Factors, Therapy, and Outcome of Leukemic Transformation of Myeloproliferative Neoplasms. , 2016, Clinical lymphoma, myeloma & leukemia.

[15]  Mario Cazzola,et al.  The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. , 2016, Blood.

[16]  S. Miyano,et al.  Profiling of somatic mutations in acute myeloid leukemia with FLT3-ITD at diagnosis and relapse. , 2015, Blood.

[17]  H. Kantarjian,et al.  Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase. , 2015, Leukemia research.

[18]  M. Voso,et al.  Azacytidine for the treatment of retrospective analysis from the Gruppo Laziale for the study of Ph-negative MPN. , 2015, Leukemia research.

[19]  M. Robin,et al.  Allo-SCT for  Philadelphia-negative myeloproliferative neoplasms in blast phase: a study from the Societe Française de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) , 2014, Bone Marrow Transplantation.

[20]  Christian Beisel,et al.  Clonal evolution and clinical correlates of somatic mutations in myeloproliferative neoplasms. , 2014, Blood.

[21]  N. Kröger,et al.  Allogeneic stem cell transplantation for myelofibrosis with leukemic transformation: a study from the Myeloproliferative Neoplasm Subcommittee of the CMWP of the European Group for Blood and Marrow Transplantation. , 2014, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[22]  M. Minden,et al.  Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms. , 2013, Blood.

[23]  O. Abdel-Wahab,et al.  Proposed criteria for response assessment in patients treated in clinical trials for myeloproliferative neoplasms in blast phase (MPN-BP): formal recommendations from the post-myeloproliferative neoplasm acute myeloid leukemia consortium. , 2012, Leukemia research.

[24]  Joshua F. McMichael,et al.  Clonal evolution in relapsed acute myeloid leukemia revealed by whole genome sequencing , 2011, Nature.

[25]  B. Quesnel,et al.  Treatment of progression of Philadelphia-negative myeloproliferative neoplasms to myelodysplastic syndrome or acute myeloid leukemia by azacitidine: a report on 54 cases on the behalf of the Groupe Francophone des Myelodysplasies (GFM). , 2010, Blood.

[26]  A. Tefferi,et al.  IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms , 2010, Leukemia.

[27]  S. Verstovsek,et al.  Allogeneic stem cell transplantation for myelofibrosis with leukemic transformation. , 2010, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[28]  H. Kantarjian,et al.  The natural history and treatment outcome of blast phase BCR-ABL- myeloproliferative neoplasms. , 2008, Blood.

[29]  R. Mesa,et al.  Leukemic transformation in myelofibrosis with myeloid metaplasia: a single-institution experience with 91 cases. , 2005, Blood.

[30]  R. A’Hern.  Sample size tables for exact single‐stage phase II designs , 2001, Statistics in medicine.

[31]  Arturo Pereira,et al.  Acute transformation in nonleukemic chronic myeloproliferative disorders: actuarial probability and main characteristics in a series of 218 patients. , 1991, Acta haematologica.