Venetoclax and decitabine in refractory TP53-mutated early T-cell precursor acute lymphoblastic leukemia

Kong, Jinyu; Chen, Nan; Li, Mengyun; Zhang, Jian; Wu, Xiaoxia; Zong, Lihong; Wu, Depei; Song, Baoquan; Qiu, Huiying

doi:10.1007/s00277-021-04530-y

Cited by 15 publications

(7 citation statements)

References 17 publications

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“…Although currently there is some evidence that T-ALL can be demethylated by hypomethylating agents (HMAs) in preclinical research, studies supporting the use of HMAs as monotherapy in clinical practices are limited. The majority of these clinical cases are often combined with additional treatment in relapsed/refractory T-ALL or ETP-ALL [24][25][26][27][28]. In our study, dec treatment showed a signi cant effect in terms of preventing T-ALL recurrence, as the 3-year CIR rate in the dec group was 11.7%, while in the ctrl group it was 35.9%.…”

Section: Discussionmentioning

confidence: 53%

Effects of post-transplant maintenance therapy with decitabine prophylaxis on the relapse for acute lymphoblastic leukemia

Fan

Zhu

et al. 2023

Bone Marrow Transplant

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In adults with acute lymphoblastic leukemia (ALL), post-transplant relapse is a major risk factor for mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Our study investigated the e cacy and safety of decitabine (dec) with ALL patients post-transplantation. We performed a retrospective cohort study to assess the e cacy of decitabine (dec) with post-transplant ALL at the First A liated Hospital of Zhengzhou University from February 2016 to September 2021. A total of 141 consecutive ALL patients were analyzed and divided into decitabine (dec, n = 65) and control (ctrl, n = 76) groups based on whether they were treated with decitabine after allo-HSCT. The 3-year cumulative incidence of relapse (CIR) rate in the dec group was lower than that in the ctrl group (19.6% vs. 36.1%, p = 0.031), with a hazard ratio of 0.491 (95% con dence interval [CI], 0.257-0.936). Additionally, subgroup analyses revealed that the 3-year CIR rate of T-ALL and Ph-negative B-ALL patients in the dec and ctrl groups was 11.7% vs. 35.9% and 19.5% vs. 42.2% (p = 0.035, p = 0.068) respectively. In summary, ALL patients, especially those with T-ALL and Ph-negative B-ALL, may bene t from decitabine as maintenance therapy following allo-HSCT.

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Section: Discussionmentioning

confidence: 53%

Effects of post-transplant maintenance therapy with decitabine prophylaxis on the relapse for acute lymphoblastic leukemia

Fan

Zhu

et al. 2023

Bone Marrow Transplant

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“…Apart from those backgrounds, there are relatively many reports on venetoclax clinical activity in T-ALL (mainly case series), but it is difficult to conclude whether this represents a more general sensitivity in T-ALL or if this is a bias of clinical decisions or reporting. However, many authors believe that venetoclax should be considered in recurrent or refractory T-ALL [ 2 , 21 , 37 , 38 , 39 , 40 , 41 ]. It is not known if there are common genomic/molecular features of those responsive T-ALL cases, apart from those mentioned above, and from the pre-clinical data on ETP-ALL and RPL10 -mutated T-ALL.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey

et al. 2023

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Venetoclax, the best established BH3 mimetic, is a practice-changing proapoptotic drug to treat blood cancers in adults. In paediatrics, the data are less but exciting results were recently presented in relapsed or refractory leukaemias demonstrating significant clinical activity. Importantly, the interventions could be potentially molecularly guided as vulnerabilities to BH3 mimetics were reported. Currently, venetoclax is not incorporated into paediatric treatment schedules in Poland but it has been already used in patients that failed conventional therapy in Polish paediatric haemato-oncology departments. The aim of the study was to gather clinical data and correlates of all paediatric patients treated thus far with venetoclax in Poland. We set out to gather this data to help choose the right clinical context for the drug and stimulate further research. The questionnaire regarding the use of venetoclax was sent to all 18 Polish paediatric haemato-oncology centres. The data of November 2022 were gathered and analysed for the diagnoses, triggers for the intervention, treatment schedules, outcomes and molecular associations. We received response from 11 centres, 5 of which administered venetoclax to their patients. Clinical benefit, in most cases consistent with haematologic complete remission (CR), was reported in five patients out of ten, whereas five patients did not show clinical benefit from the intervention. Importantly, patients with CR included subtypes expected to show venetoclax vulnerability, such as poor-prognosis ALL with TCF::HLF fusion. We believe that BH3 mimetics have clinical activity in children and should be available to paediatric haemato-oncology practitioners in well-selected applications.

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“…Venetoclax, the Bcl-2 inhibitor, is a small molecule that has shown promising therapeutic effects in AML and lymphatic malignancies. Due to its effect on the restoration of the apoptotic pathway, venetoclax as a targeted drug with a novel mechanism of action that has already demonstrated highly promising activity in others hematological malignancies such as multiple myeloma, non-Hodgkin lymphoma, myelodysplastic syndrome, and early T-cell lymphoblastic leukemia (11,12). Interestingly, Liu et al reported a novel HNRNPC-RARA fusion in APL lacking PML-RARA rearrangement, sensitive to venetoclax-based therapy.…”

Section: Discussionmentioning

confidence: 99%

Clinical Response to Venetoclax and Decitabine in Acute Promyelocytic Leukemia With a Novel RARA-THRAP3 Fusion: A Case Report

et al. 2022

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Variant acute promyelocytic leukemia (APL) showed quite different aspects, and the current treatments remained challenged at present. Venetoclax, a selective inhibitor of B-cell lymphoma 2 (BCL-2), is a small molecule that has been studied in several hematologic malignancies as both monotherapy and in combination with other agents. However, there is little of its use in the treatment of APL or variant APL. In this report, we identified THRAP3 as novel RARA fusion in resembling APL, which was resistant to all-trans retinoic acid (ATRA) combined arsenic trioxide (ATO) chemotherapy. Then, the patient was salvaged by low-dose venetoclax and decitabine. The treatment in this case demonstrates the potential ability of venetoclax in variant APL, thus providing a new treatment option for all kinds of APL.

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Venetoclax and decitabine in refractory TP53-mutated early T-cell precursor acute lymphoblastic leukemia

Cited by 15 publications

References 17 publications

Effects of post-transplant maintenance therapy with decitabine prophylaxis on the relapse for acute lymphoblastic leukemia

Effects of post-transplant maintenance therapy with decitabine prophylaxis on the relapse for acute lymphoblastic leukemia

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey

Clinical Response to Venetoclax and Decitabine in Acute Promyelocytic Leukemia With a Novel RARA-THRAP3 Fusion: A Case Report

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