Venetoclax-based therapy for relapsed or refractory acute myeloid leukaemia following intensive induction chemotherapy

Daniel Tuyet Kristensen; Rasmus Froberg Brøndum; Andreas Due Ørskov; Claus Werenberg Marcher; Claudia Schöllkopf; Anne Louise Tølbøll Sørensen; Marianne Tang Severinsen; Martin Bøgsted; Anne Stidsholt Roug

doi:10.1111/ejh.14046

Venetoclax-based therapy for relapsed or refractory acute myeloid leukaemia following intensive induction chemotherapy

Daniel Tuyet Kristensen^*, Rasmus Froberg Brøndum, Andreas Due Ørskov, Claus Werenberg Marcher, Claudia Schöllkopf, Anne Louise Tølbøll Sørensen, Marianne Tang Severinsen, Martin Bøgsted, Anne Stidsholt Roug

^*Corresponding author for this work

Department of Haematology

1 Citation (Scopus)

Abstract

BACKGROUND: The treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains challenging and outcomes extremely poor. The introduction of venetoclax has transformed the treatment of AML and emerging data suggest that venetoclax-based therapy may enforce salvage treatment.

MATERIALS AND METHODS: In this nationwide Danish retrospective study, we analysed treatment outcomes of venetoclax-based salvage treatment for R/R AML between 2019 and 2022. Only venetoclax-naive patients who had previously received treatment with intensive chemotherapy therapy were included.

RESULTS: The cohort consisted of 43 R/R patients with a median age of 57 years. Nine (20.9%) were primary refractory and 34 (79.1%) patients had relapsed, including 21 after previous allogeneic stem cell transplantation. The overall response rate was 76.2% including 61.9% with composite complete remission (CRc: CR + CRi). Among CRc-responders with information on measurable residual disease (MRD), 8/13 (61.5%) obtained an MRD-negativity response. The overall survival was 9.3 months for all patients with an estimated 1-year overall survival of 34%. For CRc-responders the median overall survival was 13.3 months, and the median relapse-free survival was 12.8 months.

CONCLUSION: Venetoclax-based salvage treatment for R/R AML produced high response rates; however, for most patients the response was of limited duration. This study is limited by an observational design and prone to selection bias.

Original language	English
Journal	European Journal of Haematology
Volume	111
Issue number	4
Pages (from-to)	573-582
Number of pages	10
ISSN	0902-4441
DOIs	https://doi.org/10.1111/ejh.14046
Publication status	Published - Oct 2023

Keywords

Antineoplastic Combined Chemotherapy Protocols/adverse effects
Chronic Disease
Humans
Induction Chemotherapy
Leukemia, Myeloid, Acute/diagnosis
Middle Aged
Neoplasm Recurrence, Local/drug therapy
Retrospective Studies
venetoclax
BCL-2
acute myeloid leukaemia
measurable residual disease
relapse/refractory

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10.1111/ejh.14046

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@article{8ac8bdfa2c654c51bd0054536289b88c,

title = "Venetoclax-based therapy for relapsed or refractory acute myeloid leukaemia following intensive induction chemotherapy",

abstract = "BACKGROUND: The treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains challenging and outcomes extremely poor. The introduction of venetoclax has transformed the treatment of AML and emerging data suggest that venetoclax-based therapy may enforce salvage treatment.MATERIALS AND METHODS: In this nationwide Danish retrospective study, we analysed treatment outcomes of venetoclax-based salvage treatment for R/R AML between 2019 and 2022. Only venetoclax-naive patients who had previously received treatment with intensive chemotherapy therapy were included.RESULTS: The cohort consisted of 43 R/R patients with a median age of 57 years. Nine (20.9%) were primary refractory and 34 (79.1%) patients had relapsed, including 21 after previous allogeneic stem cell transplantation. The overall response rate was 76.2% including 61.9% with composite complete remission (CRc: CR + CRi). Among CRc-responders with information on measurable residual disease (MRD), 8/13 (61.5%) obtained an MRD-negativity response. The overall survival was 9.3 months for all patients with an estimated 1-year overall survival of 34%. For CRc-responders the median overall survival was 13.3 months, and the median relapse-free survival was 12.8 months.CONCLUSION: Venetoclax-based salvage treatment for R/R AML produced high response rates; however, for most patients the response was of limited duration. This study is limited by an observational design and prone to selection bias.",

keywords = "Antineoplastic Combined Chemotherapy Protocols/adverse effects, Chronic Disease, Humans, Induction Chemotherapy, Leukemia, Myeloid, Acute/diagnosis, Middle Aged, Neoplasm Recurrence, Local/drug therapy, Retrospective Studies, venetoclax, BCL-2, acute myeloid leukaemia, measurable residual disease, relapse/refractory",

author = "Kristensen, {Daniel Tuyet} and Br{\o}ndum, {Rasmus Froberg} and {\O}rskov, {Andreas Due} and Marcher, {Claus Werenberg} and Claudia Sch{\"o}llkopf and S{\o}rensen, {Anne Louise T{\o}lb{\o}ll} and Severinsen, {Marianne Tang} and Martin B{\o}gsted and Roug, {Anne Stidsholt}",

note = "{\textcopyright} 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.",

year = "2023",

month = oct,

doi = "10.1111/ejh.14046",

language = "English",

volume = "111",

pages = "573--582",

journal = "European Journal of Haematology",

issn = "0902-4441",

publisher = "Wiley-Blackwell Munksgaard",

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T1 - Venetoclax-based therapy for relapsed or refractory acute myeloid leukaemia following intensive induction chemotherapy

AU - Kristensen, Daniel Tuyet

AU - Brøndum, Rasmus Froberg

AU - Ørskov, Andreas Due

AU - Marcher, Claus Werenberg

AU - Schöllkopf, Claudia

AU - Sørensen, Anne Louise Tølbøll

AU - Severinsen, Marianne Tang

AU - Bøgsted, Martin

AU - Roug, Anne Stidsholt

PY - 2023/10

Y1 - 2023/10

N2 - BACKGROUND: The treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains challenging and outcomes extremely poor. The introduction of venetoclax has transformed the treatment of AML and emerging data suggest that venetoclax-based therapy may enforce salvage treatment.MATERIALS AND METHODS: In this nationwide Danish retrospective study, we analysed treatment outcomes of venetoclax-based salvage treatment for R/R AML between 2019 and 2022. Only venetoclax-naive patients who had previously received treatment with intensive chemotherapy therapy were included.RESULTS: The cohort consisted of 43 R/R patients with a median age of 57 years. Nine (20.9%) were primary refractory and 34 (79.1%) patients had relapsed, including 21 after previous allogeneic stem cell transplantation. The overall response rate was 76.2% including 61.9% with composite complete remission (CRc: CR + CRi). Among CRc-responders with information on measurable residual disease (MRD), 8/13 (61.5%) obtained an MRD-negativity response. The overall survival was 9.3 months for all patients with an estimated 1-year overall survival of 34%. For CRc-responders the median overall survival was 13.3 months, and the median relapse-free survival was 12.8 months.CONCLUSION: Venetoclax-based salvage treatment for R/R AML produced high response rates; however, for most patients the response was of limited duration. This study is limited by an observational design and prone to selection bias.

AB - BACKGROUND: The treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains challenging and outcomes extremely poor. The introduction of venetoclax has transformed the treatment of AML and emerging data suggest that venetoclax-based therapy may enforce salvage treatment.MATERIALS AND METHODS: In this nationwide Danish retrospective study, we analysed treatment outcomes of venetoclax-based salvage treatment for R/R AML between 2019 and 2022. Only venetoclax-naive patients who had previously received treatment with intensive chemotherapy therapy were included.RESULTS: The cohort consisted of 43 R/R patients with a median age of 57 years. Nine (20.9%) were primary refractory and 34 (79.1%) patients had relapsed, including 21 after previous allogeneic stem cell transplantation. The overall response rate was 76.2% including 61.9% with composite complete remission (CRc: CR + CRi). Among CRc-responders with information on measurable residual disease (MRD), 8/13 (61.5%) obtained an MRD-negativity response. The overall survival was 9.3 months for all patients with an estimated 1-year overall survival of 34%. For CRc-responders the median overall survival was 13.3 months, and the median relapse-free survival was 12.8 months.CONCLUSION: Venetoclax-based salvage treatment for R/R AML produced high response rates; however, for most patients the response was of limited duration. This study is limited by an observational design and prone to selection bias.

KW - Antineoplastic Combined Chemotherapy Protocols/adverse effects

KW - Chronic Disease

KW - Humans

KW - Induction Chemotherapy

KW - Leukemia, Myeloid, Acute/diagnosis

KW - Middle Aged

KW - Neoplasm Recurrence, Local/drug therapy

KW - Retrospective Studies

KW - venetoclax

KW - BCL-2

KW - acute myeloid leukaemia

KW - measurable residual disease

KW - relapse/refractory

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U2 - 10.1111/ejh.14046

DO - 10.1111/ejh.14046

M3 - Journal article

C2 - 37489268

SN - 0902-4441

VL - 111

SP - 573

EP - 582

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 4

ER -

Venetoclax-based therapy for relapsed or refractory acute myeloid leukaemia following intensive induction chemotherapy

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Keywords

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