Exciting times ahead for older patients with acute myeloid leukemia: azacitidine and venetoclax followed by allogeneic hematopoietic cell transplantation

Bazarbachi, Ali

doi:10.1038/s41409-021-01474-9

Cited by 7 publications

(3 citation statements)

References 11 publications

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“…Upon reviewing the remaining 31 papers in full text, 22 were further eliminated to data unavailability or a lack of primary outcome. The nal 9 studies met the inclusion criteria [24][25][26][27][28][29][30][31][32]. The literature screening ow chart was prepared using Revman software, which is shown in Fig.…”

Section: Literature Search Resultsmentioning

confidence: 99%

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post-transplantation: a systematic review and meta-analysis

Zhang

et al. 2023

Preprint

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Background Currently, there is no standard treatment for managing relapse after allogeneic hematopoietic cell transplantation in patients with acute myeloid leukemia and myelodysplastic syndrome (AML/MDS). Venetoclax (Ven)-based therapies have been increasingly used for treating post-transplant relapse. The aim of this systematic review and meta-analysis was to evaluate the efficacy and adverse events of Ven combined with hypomethylating agents (HMAs) for AML/MDS relapse post-transplantation. Methods We searched PubMed, Web of Science, Excerpta Medica Database, Cochrane Library, and Clinical. gov for eligible studies from the inception to February 2022. The Methodological Index for Non-Randomized Studies was used to evaluate the quality of the included literature. The inverse variance method calculated the pooled proportion and 95% confidence interval (CI). Results This meta-analysis included 9 studies involving a total of 202 patients. The pooled complete response and complete response with incomplete blood count recovery rate of Ven combined with HMAs for post-transplant relapse in AML/MDS was 32% (95% CI, 25%-40%, I2 = 0%), with an overall response rate of 50% (95% CI, 40%-59%, I2 = 38%). The 6-month survival rate was 43% (95% CI, 28%-59%, I2 = 68%) and the 1-year survival rate was 27% (95% CI, 13%-42%, I2 = 72%). Conclusion This study demonstrated a moderate benefit of Ven in combination with HMAs for AML/MDS patients with relapsed post-transplantation (including those who have received prior HMAs therapy), and may become one of the treatment options in the future. Large-scale prospective studies are needed to confirm this study in future.

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Section: Literature Search Resultsmentioning

confidence: 99%

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post-transplantation: a systematic review and meta-analysis

Zhang

et al. 2023

Preprint

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“…Papeammanuil et al [28] and Prieto-Conde et al [29] have evidenced the capacity of genetic analysis (qPCR and the more discovery-powerful Next Generation Sequencing (NGS [30])) to risk stratify AML patients and inform clinical decisions. However, further improvements in treatments are still necessary, especially for older people who suffer from AML, since they often have a dismal prognosis [31] and many new treatments are too severe for this patient group [32].…”

Section: Discussionmentioning

confidence: 99%

A Combination of the Immunotherapeutic Drug Anti-Programmed Death 1 with Lenalidomide Enhances Specific T Cell Immune Responses against Acute Myeloid Leukemia Cells

Guinn

Schuler

Schrezenmeier

et al. 2023

IJMS

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Immune checkpoint inhibitors can block inhibitory molecules on the surface of T cells, switching them from an exhausted to an active state. One of these inhibitory immune checkpoints, programmed cell death protein 1 (PD-1) is expressed on T cell subpopulations in acute myeloid leukemia (AML). PD-1 expression has been shown to increase with AML progression following allo-haematopoeitic stem cell transplantation, and therapy with hypomethylating agents. We have previously shown that anti-PD-1 can enhance the response of leukemia-associated antigen (LAA)-specific T cells against AML cells as well as leukemic stem and leukemic progenitor cells (LSC/LPCs) ex vivo. In concurrence, blocking of PD-1 with antibodies such as nivolumab has been shown to enhance response rates post-chemotherapy and stem cell transplant. The immune modulating drug lenalidomide has been shown to promote anti-tumour immunity including anti-inflammatory, anti-proliferative, pro-apoptotic and anti-angiogenicity. The effects of lenalidomide are distinct from chemotherapy, hypomethylating agents or kinase inhibitors, making lenalidomide an attractive agent for use in AML and in combination with existing active agents. To determine whether anti-PD-1 (nivolumab) and lenalidomide alone or in combination could enhance LAA-specific T cell immune responses, we used colony-forming immune and ELISpot assays. Combinations of immunotherapeutic approaches are believed to increase antigen-specific immune responses against leukemic cells including LPC/LSCs. In this study we used a combination of LAA-peptides with the immune checkpoint inhibitor anti-PD-1 and lenalidomide to enhance the killing of LSC/LPCs ex vivo. Our data offer a novel insight into how we could improve AML patient responses to treatment in future clinical studies.

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“…Venetoclax and azacitidine combination therapy (VEN+AZA) is a promising novel therapy for elderly or unfit patients with acute myeloid leukemia (AML), owing to its excellent response and tolerability [ 1 , 2 ]. Recently, VEN+AZA and subsequent allo-hematopoietic stem cell transplantation (allo-HSCT) have emerged as a superior treatment, rather than VEN+AZA maintenance alone, owing to a superior outcome in patients and good tolerability for elderly and fragile patients [ 3 , 4 ]. However, the duration of response achieved by VEN+AZA is relatively short, and it is crucial to promptly find donor sources for patients who receive VEN+AZA as a bridging treatment to allo-HSCT.…”

Section: Introductionmentioning

confidence: 99%

Venetoclax-Azacitidine Bridging PTCy-haplo-PBSCT for Refractory Acute Myeloid Leukemia with <i>IDH2</i> Mutations

Daido,

Sugiura,

Ishikawa

et al. 2023

Case Rep Oncol

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Venetoclax and azacitidine combination therapy (VEN+AZA) is a promising novel therapy for elderly or unfit patients with acute myeloid leukemia (AML). Recently, VEN+AZA with subsequent allo-hematopoietic stem cell transplantation has been reported, and human leukocyte antigen-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haplo-PBSCT) from related donors appears to be a suitable option. Here, we report two elderly patients with refractory AML harboring an <i>IDH2</i> mutation, who were successfully treated with VEN+AZA bridged to PTCy-haplo-PBSCT. This report suggests the efficacy and safety of VEN+AZA as a bridging treatment for PTCy-haplo-PBSCT in refractory AML.

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Exciting times ahead for older patients with acute myeloid leukemia: azacitidine and venetoclax followed by allogeneic hematopoietic cell transplantation

Cited by 7 publications

References 11 publications

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post-transplantation: a systematic review and meta-analysis

Efficacy and safety of venetoclax combined with hypomethylating agents for relapse of acute myeloid leukemia and myelodysplastic syndrome post-transplantation: a systematic review and meta-analysis

A Combination of the Immunotherapeutic Drug Anti-Programmed Death 1 with Lenalidomide Enhances Specific T Cell Immune Responses against Acute Myeloid Leukemia Cells

Venetoclax-Azacitidine Bridging PTCy-haplo-PBSCT for Refractory Acute Myeloid Leukemia with <i>IDH2</i> Mutations

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