|Table of Contents|

Clinical observation of venetoclax combined with high-dose cytarabine in relapsed/refractory AML

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 16
Page:
3060-3065
Research Field:
Publishing date:

Info

Title:
Clinical observation of venetoclax combined with high-dose cytarabine in relapsed/refractory AML
Author(s):
LEI XiaoruDAI JinqianLI QiaoyanSHI RuiWEN JingWU WenREN JingjingLI GuangSONG Yanping
Institute of Hematology of Xi'an,Xi'an Central Hospital,Shaanxi Xi'an 710004,China.
Keywords:
venetoclaxcytarabinerelapsed/refractory acute myeloid leukemia
PACS:
R733.7
DOI:
10.3969/j.issn.1672-4992.2024.16.019
Abstract:
Objective:To investigate the efficacy and safety of venetoclax (VEN) combined with high-dose cytarabine (HiDAC) regimen for relapsed or refractory acute myeloid leukemia (R/R AML).Methods:The clinical data of 31 adult R/R AML patients who received the combination of VEN with HiDAC in our institute from June 2019 to November 2023 were retrospectively analyzed.To evaluate the treatment response,adverse events and survival,and explore the factors influencing the efficacy and survival.Results:The overall response rate (ORR) of 31 patients was 77.4% (24 cases),including 20 cases of complete response (CR) and CR with incomplete count recovery (CRi) and morphological leukemic free status (MLFS).4 cases of partial response(PR).Relapse and refractory status had no significant effect on ORR and CRc (P>0.05),with no statistically significant difference in overall survival (OS) and event-free survival (EFS) between the two groups (P>0.05).The median OS of all the patients was 10.8 (3.5~36) months and median EFS was 8.5(0.5~32) months.The survival analysis showed that the patients who responded to the first treatment had a better OS and EFS (P<0.01).The patients (13 cases) who treated with bridge allogeneic hematopoietic stem cell transplantation (allo-HSCT) had superior OS and EFS than the patients (18 cases) treated with continue chemotherapy (both P<0.01).Adverse effects were mainly bone marrow suppression.All patients had experienced≥Ⅲ grade hematologic toxicity.Infection and gastrointestinal discomfort was common,but these could be all tolerated by patients.There were no treatment related deaths.Conclusion:VEN combined with HiDAC regimen is an effective salvage therapy for patients with R/R AML and is well tolerated by patients.Bridging allo-HSCT can improve long-term survival of patients.

References:

[1]THOL F,GANSER A.Treatment of relapsed acute myeloid leukemia[J].Curr Treat Options Oncol,2020,21(8):66.
[2]GANZEL C,SUN Z,CRIPE LD,et al.Very poor long-term survival in past and more recent studies for relapsed AML patients:The ECOG-ACRIN experience[J].Am J Hematol,2018,93(8):1074-1081.
[3]ROBERTS AW.Therapeutic development and current uses of BCL-2 inhibition[J].Hematology Am Soc Hematol Educ Program,2020,2020(1):1-9.
[4]BAZINET A,GARCIA-MANERO G,SHORT N,et al.Oral decitabine and cedazuridine plus venetoclax for older or unfit patients with acute myeloid leukaemia:a phase 2 study[J].Lancet Haematol,2024,3:4.
[5]WEI AH,STRICKLAND SA JR,HOU JZ,et al.Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia:results from a phase Ib/II study[J].J Clin Oncol,2019,37(15):1277-1284.
[6]中华医学会血液学分会白血病淋巴瘤学组.中国复发难治性急性髓系白血病诊疗指南(2021年版)[J].中华血液学杂志,2021,42(8):624-627. Leukemia & Lymphoma Group,Chinese Society of Hematology,Chinese Medical Association.Chinese guidelines for the diagnosis and treatment of relapsed/refractory acute myelogenous leukemia (2021) [J].Chin J Hematol,2021,42(8):624-627.
[7]范晨阳,许鑫欣,孙维龙,等.维奈克拉联合用药治疗急性髓细胞白血病作用机制的研究现状[J].国际输血及血液学杂志,2021,44(5):376-382. FAN CY,XU XX,SUN WL,et al.Research status in mechanisms of venetoclax combined with other drugs for treatment of acute myeloid leukemia[J].Int J Blood Transfus Hematol,2021,44(5):376-382.
[8]ASAULENKO ZP,SPIRIDONOV IN.WHO classification of tumors of hematopoietic and lymphoid tissues,2022 (5th edition):Myeloid and histiocytic tumors[J].Arkh Patol,2023,85(5):36-44.
[9]DOHNER H,ESTEY E,GRIMWADE D,et al.Diagnosis and management of AML in adults:2017 ELN recommendations from an international expert panel[J].Blood,2017,129(4):424-447.
[10]FREITES-MARTINEZ A,SANTANA N.Using the common terminology criteria for adverse events (CTCAE-Version 5.0) to evaluate the severity of adverse events of anticancer therapies.CTCAE versión 5.0.Evaluación de la gravedad de los eventos adversos dermatológicos de las terapias antineoplásicas[J].Actas Dermosifiliogr (Engl Ed),2021,112(1):90-92.
[11]BEWERSDORF JP,GIRI S,WANG R,et al.Venetoclax as monotherapy and in combination with hypomethylating agents or low dose cytarabine in relapsed and treatment refractory acute myeloid leukemia:a systematic review and meta-analysis[J].Haematologica,2020,105(11):2659-2663.
[12]STAHL M,MENGHRAJANI K,DERKACH A,et al.Clinical and molecular predictors of response and survival following venetoclax therapy in relapsed/refractory AML[J].Blood Adv,2021,5(5):1552-1564.
[13]宗李红,吴小霞,吴德沛,等.维奈克拉联合阿扎胞苷治疗难治复发性急性髓系白血病疗效及安全性分析[J].中华血液学杂志,2021,42(10):861-864. ZONG LH,WU XX,WU DP,et al.Efficacy and safety of venetoclax and azacitidine in the treatment of refractory and relapsed acute myeloid leukemia[J].Chin J Hematol,2021,42(10):861-864.
[14]YOU L,LIU Y,MAI W,et al.Venetoclax plus cytarabine and azacitidine in relapsed/refractory AML:An open-label,single-arm,phase 2 study[J].Eur J Cancer,2024,3:1.
[15]JIN H,ZHANG Y,YU S,et al.Venetoclax combined with azacitidine and homoharringtonine in relapsed/refractory AML:A multicenter,phase 2 trial[J].J Hematol Oncol,2023,16(1):42.
[16]KAROL SE,ALEXANDER TB,BUDHRAJA A,et al.Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia:a phase 1,dose-escalation study[J].Lancet Oncol,2020,21(4):551-560.
[17]ZIELONKA K,JAMROZIAK K.Mechanisms of resistance to venetoclax in hematologic malignancies[J].Adv Clin Exp Med,2024,3:1.
[18]DOUSSET C,MAIGA S,GOMEZ-BOUGIE P,et al.BH3 profiling as a tool to identify acquired resistance to venetoclax in multiple myeloma[J].Br J Haematol,2017,179(4):684-688.
[19]ENGEN C,HELLESOY M,GROB T,et al.FLT3-ITD mutations in acute myeloid leukaemia-molecular characteristics,distribution and numerical variation[J].Mol Oncol,2021,15(9):2300-2317.
[20]PERL AE,LARSON RA,PODOLTSEV NA,et al.Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial[J].Blood,2022,139(23):3366-3375.
[21]MCMAHON CM,CANAANI J,REA B,et al.Gilteritinib induces differentiation in relapsed and refractory FLT3-mutated acute myeloid leukemia[J].Blood Adv,2019,3(10):1581-1585.
[22]MCMAHON CM,FERNG T,CANAANI J,et al.Clonal selection with RAS pathway activation mediates secondary clinical resistance to selective FLT3 inhibition in acute myeloid leukemia[J].Cancer Discov,2019,9(8):1050-1063.
[23]NUMAN Y,ABDEL RANMAN Z,GRENET J,et al.Gilteritinib clinical activity in relapsed/refractory FLT3 mutated acute myeloid leukemia previously treated with FLT3 inhibitors[J].Am J Hematol,2022,97(3):322-328.
[24]CHEN N,PAN J,ZHOU Y,et al.Gilteritinib-based combination therapy in adult relapsed/refractory FLT3-mutated acute myeloid leukaemia[J].Br J Haematol,2023,11:8.
[25]MOLICA M,MAZZONE C,NISCOLA P,et al.TP53-mutations in acute myeloid leukemia:Still a daunting challenge[J].Front Oncol,2021,10:610820.

Memo

Memo:
陕西省西安市科技计划项目(编号:21YXYJ0017)
Last Update: 1900-01-01