Venetoclax combined with azacitidine as an effective and safe salvage regimen for relapsed or refractory T-cell acute lymphoblastic leukemia: a case series

Wan, Chao‐Ling; Zou, Jing-Ying; Qiao, Man; Yin, Jia; Shen, Xiang‐Dong; Qiu, Qiao‐Cheng; Liu, Song‐Bai; Xue, Sheng‐Li

doi:10.1080/10428194.2021.1957876

Cited by 16 publications

(7 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…125 In a separate study of relapsed/ refractory T-ALL, five adult patients were salvaged when treated with a combination of venetoclax (BCL2 inhibitor) and decitabine. 126,127 For clinical cases that underwent allogenic hematopoietic stem cell transplantation (allo-HSCT), one study showed that low dose decitabine after allo-HSCT prevented relapse in 7/7 T-ALL patients (including one ETP-ALL case) 128 and another study showed that combining decitabine with venetoclax prevented relapse in 4/4 T-ALL patients up to 15 months after transplant. 126,127 Taken together, these studies all provide strong support for the use of decitabine as a maintenance therapy in T-ALL.…”

Section: T-all Relapse Chemo-resistance and Epigeneticsmentioning

confidence: 99%

“…126,127 For clinical cases that underwent allogenic hematopoietic stem cell transplantation (allo-HSCT), one study showed that low dose decitabine after allo-HSCT prevented relapse in 7/7 T-ALL patients (including one ETP-ALL case) 128 and another study showed that combining decitabine with venetoclax prevented relapse in 4/4 T-ALL patients up to 15 months after transplant. 126,127 Taken together, these studies all provide strong support for the use of decitabine as a maintenance therapy in T-ALL. [129][130][131] The HDACi Givinostat exerted robust cytotoxic effect and induction of DNA damage (increased phospho-H2AX levels) in vivo for the treatment of T-ALL pediatric PDXs (n = 9).…”

Section: T-all Relapse Chemo-resistance and Epigeneticsmentioning

confidence: 99%

“…ChiCTR1800014888 [125][126][127][128] Using mouse xenografts, it was identified that 5-azacytidine treated hypermethylated T-ALL samples showed delayed tumor progression.…”

Section: Histone Methyltransferase (Hmt) and Histone Demethylase (Hdm...mentioning

confidence: 99%

See 2 more Smart Citations

The landscape of alterations affecting epigenetic regulators in T‐cell acute lymphoblastic leukemia: Roles in leukemogenesis and therapeutic opportunities

Walia,

de Bock,

Huang

2023

Intl Journal of Cancer

View full text Add to dashboard Cite

T‐cell acute lymphoblastic leukemia (T‐ALL) is an aggressive malignancy accounting for 10%–15% of pediatric and 20%–25% of adult ALL cases. Epigenetic irregularities in T‐ALL include alterations in both DNA methylation and the post‐translational modifications on histones which together play a critical role in the initiation and development of T‐ALL. Characterizing the oncogenic mutations that result in these epigenetic changes combined with the reversibility of epigenetic modifications represents an opportunity for the development of epigenetic therapies. Oncogenic mutations and deregulated expression of DNA methyltransferases (DNMTs), Ten‐Eleven Translocation dioxygenases (TETs), Histone acetyltransferases (HATs) and members of Polycomb Repressor Complex 2 (PRC2) have all been identified in T‐ALL. This review focuses on the current understanding of how these mutations lead to epigenetic changes in T‐ALL, their association with disease pathogenesis and the current efforts to exploit these clinically through the development of epigenetic therapies in T‐ALL treatment.

show abstract

Section: T-all Relapse Chemo-resistance and Epigeneticsmentioning

confidence: 99%

Section: T-all Relapse Chemo-resistance and Epigeneticsmentioning

confidence: 99%

See 1 more Smart Citation

The landscape of alterations affecting epigenetic regulators in T‐cell acute lymphoblastic leukemia: Roles in leukemogenesis and therapeutic opportunities

Walia,

de Bock,

Huang

2023

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…With the cutting‐edge progress in precision medicine, genetic aberrations‐directed targeted therapies are becoming extremely important in T‐ALL 1 . Previous studies showed that venetoclax (Abbvie, an orally inhibitor selective for BCL‐2) and DNA hypomethylating agents like azacytidine are likely to work synergistically to extirpate relapsed T‐ALL 2 . However, relapse or resistance to treatment in T‐ALL patients remains a clinical challenge.…”

Section: Introductionmentioning

confidence: 99%

Targeted therapy using larotrectinib and venetoclax for the relapsed/refractory T‐cell acute lymphoblastic leukemia harboring a cryptic ETV6‐NTRK3 fusion

Zhou

Gong

et al. 2023

Molecular Carcinogenesis

View full text Add to dashboard Cite

Outcomes for patients with relapsed and refractory (R/R) T-cell acute lymphoblastic leukemia (T-ALL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are dismal, with few available treatments. Recently, identification of cancer patients harboring neurotrophic tropomyosin receptor kinase (NTRK) gene fusions is constantly increasing, especially with the advent of NTRK inhibitors. However, the role of ETV6-NTRK3 in T-ALL has not been investigated. This case represented the first detailed report of T-ALL patient harboring a cryptic ETV6-NTRK3 fusion with an unfavorable prognosis, not only because of leukemia resistant to the standard multiagent chemotherapy but also early relapse after allo-HSCT. Acquired EP300 mutation was found at relapse, which could explain the cause of recurrence and affect the follow-up treatment. Combined targeted therapy like larotrectinib allied with pan-targeted BCL-2 inhibitor venetoclax, may be a potential maintenance treatment in R/R ETV6-NTRK3 positive leukemia after allo-HSCT. The leukemic clonal evolution might be revealed through transcriptome sequencing and overcome by drugs with universal targets. Our case demonstrated that both comprehensive profiling techniques (such as transcriptome sequencing, multiparameter flow cytometry, and digital droplet polymerase chain reaction) and a multimodality treatment strategy were critical for anticipating an early relapse and personalized therapy of R/R T-cell leukemia.

show abstract

“…Both HMAs and the BCL-2 inhibitor venetoclax possess significant antitumor activity effects against acute myeloid leukemia/myelodysplastic syndrome and their efficacy in R/R T-ALL has been demonstrated in multiple case series [14]. T-ALL exhibited high in-vitro and in-vivo sensitivity to the BCL-2 inhibitor, venetoclax in correspondence with high levels of BCL-2 [15].…”

mentioning

confidence: 99%

Azacitidine in Combination with Venetoclax Maintenance Post-allogeneic Hematopoietic Stem Cell Transplantation in T Cell Acute Lymphoblastic Leukemia

et al. 2023

View full text Add to dashboard Cite

Venetoclax combined with azacitidine as an effective and safe salvage regimen for relapsed or refractory T-cell acute lymphoblastic leukemia: a case series

Cited by 16 publications

References 8 publications

The landscape of alterations affecting epigenetic regulators in T‐cell acute lymphoblastic leukemia: Roles in leukemogenesis and therapeutic opportunities

The landscape of alterations affecting epigenetic regulators in T‐cell acute lymphoblastic leukemia: Roles in leukemogenesis and therapeutic opportunities

Targeted therapy using larotrectinib and venetoclax for the relapsed/refractory T‐cell acute lymphoblastic leukemia harboring a cryptic ETV6‐NTRK3 fusion

Azacitidine in Combination with Venetoclax Maintenance Post-allogeneic Hematopoietic Stem Cell Transplantation in T Cell Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About