[Clinical Efficacy and Safety of Venetoclax Combined with Multidrug Chemotherapy in the Treatment of 15 Patients with Relapsed or Refractory Early T-cell Precursor Acute Lymphoblastic Leukemia]

Overview

Journal Zhonghua Xue Ye Xue Za Zhi

Specialty Hematology

Date 2023 Oct 7

PMID 37803838

Authors

J Y Kong

L H Zong

Y Pu

Y Liu

X Kong

M Y Li

J Zhang

B Q Song

S L Xue

X W Tang

H Y Qiu

D P Wu

Affiliations

Soon will be listed here.

Abstract

To explore the efficacy and safety of Venetoclax combined with multidrug chemotherapy in patients with relapsed or refractory early T-cell precursor acute lymphoblastic leukemia (R/R ETP-ALL) . This study retrospectively analyzed 15 patients with R/R ETP-ALL who received Venetoclax combined with multidrug chemotherapy from December 2018 to February 2022. Among them, eight cases were combined with demethylated drugs, four cases were combined with demethylated drugs and HAAG chemotherapy regimen, two cases were combined with demethylated drugs and CAG regimen, and one case was combined with Cladribine. Specific usage and dosage of Venetoclax: 100 mg on day 1, 200 mg on day 2, 400 mg on day 3-28, orally; when combined with azole antifungal drugs, dosage was reduced to 100 mg/d. Fifteen patients (10 males and 5 females) with R/R ETP-ALL were treated with Venetoclax and multidrug chemotherapy with a median age of 35 (12-42) years old. Of 4 refractory and 11 relapsed patients, the efficacy was evaluated on the 21th day following combined chemotherapy: the overall response rate, the complete response (CR) rate, and the CR with incomplete hematological recovery (CRi) rate were 67.7% (10/15), 60.0% (9/15), and 6.7% (1/15), respectively. For the overall study population, the 12-month overall survival (OS) rate was 60.0%, and the median OS was 17.7 months. The disease-free survival (DFS) rate of all CR patients at 12 months was 60.0%, and the median DFS did not reach. About 14 patients had Ⅲ-Ⅳ hematological toxicity, but these adverse reactions were all controllable. No adverse reaction in the nervous system and tumor lysis syndrome occurred in this study, and no adverse reaction of organs above grade Ⅲ occurred. Venetoclax combined with multidrug chemotherapy may be a safe and promising treatment option for patients with R/R ETP-ALL.

References

Morita K, Jain N, Kantarjian H, Takahashi K, Fang H, Konopleva M . Outcome of T-cell acute lymphoblastic leukemia/lymphoma: Focus on near-ETP phenotype and differential impact of nelarabine. Am J Hematol. 2021; 96(5):589-598. DOI: 10.1002/ajh.26144. View

La Starza R, Cambo B, Pierini A, Bornhauser B, Montanaro A, Bourquin J . Venetoclax and Bortezomib in Relapsed/Refractory Early T-Cell Precursor Acute Lymphoblastic Leukemia. JCO Precis Oncol. 2020; 3. PMC: 7448796. DOI: 10.1200/PO.19.00172. View

Bond J, Graux C, Lhermitte L, Lara D, Cluzeau T, Leguay T . Early Response-Based Therapy Stratification Improves Survival in Adult Early Thymic Precursor Acute Lymphoblastic Leukemia: A Group for Research on Adult Acute Lymphoblastic Leukemia Study. J Clin Oncol. 2017; 35(23):2683-2691. DOI: 10.1200/JCO.2016.71.8585. View

Peirs S, Matthijssens F, Goossens S, Van de Walle I, Ruggero K, de Bock C . ABT-199 mediated inhibition of BCL-2 as a novel therapeutic strategy in T-cell acute lymphoblastic leukemia. Blood. 2014; 124(25):3738-47. DOI: 10.1182/blood-2014-05-574566. View

Numan Y, Alfayez M, Maiti A, Alvarado Y, Jabbour E, Ferrajoli A . First report of clinical response to Venetoclax in Early T-cell Precursor Acute Lymphoblastic Leukemia. JCO Precis Oncol. 2019; 2. PMC: 6508880. DOI: 10.1200/PO.18.00127. View

Rahmat L, Nguyen A, Abdulhaq H, Prakash S, Logan A, Mannis G . Venetoclax in Combination with Decitabine for Relapsed T-Cell Acute Lymphoblastic Leukemia after Allogeneic Hematopoietic Cell Transplant. Case Rep Hematol. 2018; 2018:6092646. PMC: 6129347. DOI: 10.1155/2018/6092646. View

Xu X, Zhai Q, Jin H, Yu Y, Han D, Zhang H . Fusion Gene Involved Early T-Cell Precursor Acute Lymphoblastic Leukemia in Adult with B Marker Expression. Int J Gen Med. 2021; 14:659-664. PMC: 7920624. DOI: 10.2147/IJGM.S294715. View

Anderson N, Harrold I, Mansour M, Sanda T, McKeown M, Nagykary N . BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more-differentiated T-ALL cell lines. Leukemia. 2013; 28(5):1145-8. PMC: 4013222. DOI: 10.1038/leu.2013.377. View

Zhang X, Li J, Jin J, Yu W . Relapsed/refractory early T-cell precursor acute lymphoblastic leukemia was salvaged by venetoclax plus HAG regimen. Ann Hematol. 2019; 99(2):395-397. DOI: 10.1007/s00277-019-03902-9. View

10.

Wan C, Zou J, Qiao M, Yin J, Shen X, Qiu Q . Venetoclax combined with azacitidine as an effective and safe salvage regimen for relapsed or refractory T-cell acute lymphoblastic leukemia: a case series. Leuk Lymphoma. 2021; 62(13):3300-3303. DOI: 10.1080/10428194.2021.1957876. View

11.

Liu S, Cui Q, Dai H, Song B, Cui W, Xue S . Early T-Cell Precursor Acute Lymphoblastic Leukemia and T/Myeloid Mixed Phenotype Acute Leukemia Possess Overlapping Characteristics and Both Benefit From CAG-Like Regimens and Allogeneic Hematopoietic Stem Cell Transplantation. Transplant Cell Ther. 2021; 27(6):481.e1-481.e7. DOI: 10.1016/j.jtct.2021.02.032. View

12.

Castaneda Puglianini O, Papadantonakis N . Early precursor T-cell acute lymphoblastic leukemia: current paradigms and evolving concepts. Ther Adv Hematol. 2020; 11:2040620720929475. PMC: 7370557. DOI: 10.1177/2040620720929475. View