venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

Simona Sica

venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

Simona Sica

Research output: Contribution to journal › Article

Abstract

venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

Original language	English
Pages (from-to)	101-103
Number of pages	3
Journal	Bone Marrow Transplantation
Issue number	1
Publication status	Published - 2026

Keywords

Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia
stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus process. Results: The panel achieved a high degree of agreement on specific interventions covering diagnostic testing
upfront FLT3i integration
role of allogeneic hematopoietic cell transplantation (allo-HSCT)
Minimal Residual Disease (MRD) monitoring
and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis
with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients
the current standard of HMA + venetoclax is considered suboptimal
making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting
retesting the FLT3 status is mandatory
and gilteritinib is the standard treatment
serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category
enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide
translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population.

Cite this

@article{dbc0ea67c2cc4bfa855b05af43137aed,

title = "venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT",

abstract = "venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT",

keywords = "Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia, stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus process. Results: The panel achieved a high degree of agreement on specific interventions covering diagnostic testing, upfront FLT3i integration, role of allogeneic hematopoietic cell transplantation (allo-HSCT), Minimal Residual Disease (MRD) monitoring, and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis, with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients, the current standard of HMA + venetoclax is considered suboptimal, making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting, retesting the FLT3 status is mandatory, and gilteritinib is the standard treatment, serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category, enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide, translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population., Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia, stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus process. Results: The panel achieved a high degree of agreement on specific interventions covering diagnostic testing, upfront FLT3i integration, role of allogeneic hematopoietic cell transplantation (allo-HSCT), Minimal Residual Disease (MRD) monitoring, and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis, with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients, the current standard of HMA + venetoclax is considered suboptimal, making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting, retesting the FLT3 status is mandatory, and gilteritinib is the standard treatment, serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category, enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide, translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population.",

author = "Simona Sica",

year = "2026",

language = "English",

pages = "101--103",

journal = "Bone Marrow Transplantation",

issn = "0268-3369",

publisher = "Springer Nature",

number = "1",

}

TY - JOUR

T1 - venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

AU - Sica, Simona

PY - 2026

Y1 - 2026

N2 - venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

AB - venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

KW - Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia

KW - stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus

KW - upfront FLT3i integration

KW - role of allogeneic hematopoietic cell transplantation (allo-HSCT)

KW - Minimal Residual Disease (MRD) monitoring

KW - and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis

KW - with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients

KW - the current standard of HMA + venetoclax is considered suboptimal

KW - making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting

KW - retesting the FLT3 status is mandatory

KW - and gilteritinib is the standard treatment

KW - serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category

KW - enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide

KW - translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population.

KW - Background/Objectives: The emergence of FLT3 inhibitors (FLT3i) has radically transformed the prognostic and therapeutic landscape for FLT3-mutated Acute Myeloid Leukemia

KW - stimulating the need for comprehensive and structured clinical guidance. Methods: We aimed to develop evidence-based recommendations spanning the entire disease continuum of FLT3-mutated AML from leading Italian experts through a modified Delphi consensus

KW - upfront FLT3i integration

KW - role of allogeneic hematopoietic cell transplantation (allo-HSCT)

KW - Minimal Residual Disease (MRD) monitoring

KW - and relapsed/refractory (R/R) strategies. Key recommendations mandate that analysis for both FLT3-ITD and FLT3-TKD mutations is required at diagnosis

KW - with capillary electrophoresis or NGS as preferred methods. All fit patients with FLT3m-AML must receive intensive chemotherapy plus a FLT3i (midostaurin or quizartinib) and be evaluated for allo-HSCT. For unfit patients

KW - the current standard of HMA + venetoclax is considered suboptimal

KW - making the search for alternative strategies imperative. MRD monitoring using available molecular or flow cytometry markers is recommended to assess relapse risk and to optimize the allo-HSCT strategy. In the R/R setting

KW - retesting the FLT3 status is mandatory

KW - and gilteritinib is the standard treatment

KW - serving as a bridge-to-transplant and for post-HSCT maintenance. Conclusions: The integration of FLT3i has shifted FLT3m-AML into a more favorable intermediate prognostic category

KW - enhancing the role of curative strategies like allo-HSCT. This consensus paper provides a structured evidence-based comprehensive guide

KW - translating complex data into clear actionable clinical recommendations that minimize practice variability and ultimately optimize management for this high-risk population.

UR - https://publicatt.unicatt.it/handle/10807/336066

M3 - Article

SN - 0268-3369

SP - 101

EP - 103

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 1

ER -

venetoclax plus hypomethylating agents as first salvage therapy for myeloid malignancies relapsing after allogenic HSCT

Abstract

Keywords

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