Efficacy of Decitabine and Venetoclax as Salvage and Bridge Therapy to Haploidentical Hematopoietic Stem Cell Transplantation in a Multiresistant Acute Myeloid Leukemia Patient

Abstract

Treatment of relapsed/refractory or elderly unfit acute myeloid leukemia (AML) is still challenging, and hypomethylating agents in combination with venetoclax, an oral selective BCL2 inhibitor, might be successfully used as salvage therapy. However, clinical trials evaluating the efficacy and safety of this combination in the setting of multiresistant AML treatment also as a bridge to transplant are still ongoing. Here, we reported a 50-year-old male diagnosed with AML with normal cytogenetics and wild type for fms-like tyrosine kinase 3, nucleophosmin 1, and KIT, and treated with decitabine and venetoclax as the fifth line of therapy and after a relapse post-allogeneic transplant. The patient achieved a complete remission and successfully underwent a haploidentical transplant with an overall survival of 48.6 months.

Clinical efficacy of azacytidine and venetoclax and prognostic impact of Tim-3 and galectin-9 in acute myeloid leukemia and high-risk myelodysplastic syndromes: A single-center real-life experience

“…Therefore, alternative more manageable therapeutic strategies are required. Hypomethylating agents, such as azacytidine and decitabine, have become a milestone in treatment of older AML and high-risk MDS patients with good efficacy and safety profile ( Serio B et al, 2022 ). In 2018, the Bcl-2 inhibitor venetoclax has been added to hypomethylating agents or low-dose cytarabine for treatment of newly diagnosed AML patients aged 75 or older not eligible for high-dose standard chemotherapy based on phase III clinical trial results ( DiNardo CD et al, 2020 ; Stein EM et al, 2020 ; Pollyea DA et al, 2021 ; Labrador J et al, 2022 ; Mustafa Ali MK et al, 2022 ; Wolach O et al, 2022 ).…”

“…An ongoing phase I clinical trial is investigating efficacy and safety of anti-Tim-3 monoclonal antibody associated with a standard-of-care, decitabine, for MDS and AML showing promising preliminary results and paving the way for its potential use in hematologic malignancies ( Borate U et al, 2019 ; Achrya et al, 2020 ). Hypomethylating agents, including azacytidine and decitabine, are a milestone in MDS and AML treatment, especially in older patients not eligible for hematopoietic stem cell transplantation (HSCT) ( Serio B et al, 2022 ). These nucleoside derivatives interfere with DNA methyltransferases (DNMT) and reinduce the transcription of silenced genes and re-programming gene expression, as hypermethylation, gene silencing, and other epigenetic modifications, are a signature of myelodysplasia ( Roulois D et al, 2015 ).…”

Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition

“…1 AML, a heterogeneous group of clonal aggressive hematologic malignancies, is characterized by increased proliferation of poorly differentiated myeloid neoplastic cells harboring various cytogenetic abnormalities. 2 Genetic and epigenetic alterations are considered the main pathogenetic events for the development of MDS and AML, as somatic mutations in driver genes lead to modifications in gene expression and increased cell survival and proliferation. 3,4 Indeed, recurrent somatic mutations are detected in more than 80% of MDS patients, usually six per exome in low-risk MDS and nine in MDS with excess blasts, in a restrict set of driver genes, categorized into nine distinct functional pathways, such as DNA methylation (e.g., DNMT3A and TET2), or chromatin modification genes (e.g., EZH2 and ASXL1).…”

“…Myelodysplastic syndromes (MDS), a heterogeneous group of clonal malignant hematological diseases, are characterized by ineffective hematopoiesis, peripheral blood cytopenia(s), and increased risk of acute myeloid leukemia (AML) with poor prognosis 1 . AML, a heterogeneous group of clonal aggressive hematologic malignancies, is characterized by increased proliferation of poorly differentiated myeloid neoplastic cells harboring various cytogenetic abnormalities 2 . Genetic and epigenetic alterations are considered the main pathogenetic events for the development of MDS and AML, as somatic mutations in driver genes lead to modifications in gene expression and increased cell survival and proliferation 3,4 .…”

Persistent decreased bone marrow CD3+CD56+ T lymphocytes are inversely associated with mature granulocytes in myelodysplastic syndromes

“…1 To support Leone's findings, we retrospectively investigated BM frequency of CD3 + CD56 + T lymphocytes, and we compared those frequencies to granulocyte maturation and WT1 expression levels, a well-known prognostic marker in hematological malignancies. 2 A total of 44 consecutive patients were included in this study after received diagnosis of AML or MDS. [3][4][5][6][7][8] Clinical characteristics are summarized in Figure 1A.…”