Abstract
Introduction: The combination of venetoclax (VEN) and azacytidine (AZA) has demonstrated potential in achieving rapid and effective remissions in elderly patients with acute myeloid leukemia (AML). Allogeneic hematopoietic stem cell transplantation is a promising potential cure for high-risk AML, as VEN-based therapies have a worse prognosis in elderly patients. This study aimed to assess the efficacy of sequential haploidentical HSCT following two courses of VEN and AZA therapy in patients with AML aged 55 years and older. Methods: We conducted a retrospective study on AML patients aged 55–70 years who received intensive chemotherapy or two courses of VEN/AZA therapy, followed by haploidentical allo-HSCT (haplo-HSCT) based on disease risk degree, measurable residual disease status, and patient’s preference. Results: Between January 2019 and December 2023, 141 newly diagnosed AML patients received initial treatment with intensive chemotherapy or VEN/AZA therapy. Among them, 64 patients received haplo-HSCT, while 77 did not. The 1-year overall survival (OS) and relapse-free survival (RFS) of patients who received haplo-HSCT were significantly higher than those who did not receive haplo-HSCT (p < 0.05). Among patients who received transplantation, there was no significant difference in 1-year OS and RFS between the VEN/AZA and intensive chemotherapy groups: 76.3% versus 69.3% (p = 0.367) for OS, and 74.5% versus 69.7% (p = 0.473) for RFS. High-risk ELN stratification and the presence of ≥4 gene mutations were associated with lower OS and RFS in both univariate and multivariate analyses. Conclusions: AML patients over 55 years of age who received haplo-HSCT after two courses of VEN/AZA therapy had outcomes similar to those who received haplo-HSCT after intensive chemotherapy, suggesting that two courses of VEN/AZA therapy as a bridge to haplo-HSCT are feasible for patients over 55 years old.
Journal Section:
Original Paper
References
1.
Global Burden of Disease Cancer Collaboration
, Fitzmaurice
C
, Abate
D
, Abbasi
N
, Abbastabar
H
, Abd-Allah
F
, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study
. JAMA Oncol
. 2019
;5
(12
):1749
–68
. 2.
Shallis
RM
, Wang
R
, Davidoff
A
, Ma
X
, Zeidan
AM
. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges
. Blood Rev
. 2019
;36
:70
–87
. 3.
Sasaki
K
, Ravandi
F
, Kadia
TM
, DiNardo
CD
, Short
NJ
, Borthakur
G
, et al. De novo acute myeloid leukemia: a population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017
. Cancer
. 2021
;127
(12
):2049
–61
. 4.
Ossenkoppele
G
, Lowenberg
B
. How I treat the older patient with acute myeloid leukemia
. Blood
. 2015
;125
(5
):767
–74
. 5.
Stone
A
, Zukerman
T
, Flaishon
L
, Yakar
RB
, Rowe
JM
. Efficacy outcomes inthe treatment of older or medically unfit patients with acute myeloid leukaemia:a systematic review and meta-analysis
. Leuk Res
. 2019
;82
:36
–42
. 6.
Hilberink
J
, Hazenberg
C
, van den Berg
E
, Mulder
A
, Schuringa
JJ
, van der Helm
L
, et al. Not type of induction therapybut consolidation with allogeneic hematopoietic cell transplantationdetermines outcome in older AML patients: a singlecenter experience of355 consecutive patients
. Leuk Res
. 2019
;80
:33
–9
. 7.
DiNardo
CD
, Jonas
BA
, Pullarkat
V
, Thirman
MJ
, Garcia
JS
, Wei
AH
, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia
. N Engl J Med
. 2020
;383
(7
):617
–29
. 8.
Wei
AH
, Montesinos
P
, Ivanov
V
, DiNardo
CD
, Novak
J
, Laribi
K
, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial
. Blood
. 2020
;135
(24
):2137
–45
. 9.
Pollyea
DA
, Pratz
K
, Letai
A
, Jonas
BA
, Wei
AH
, Pullarkat
V
, et al. Venetoclax with azacitidine or decitabinein patients with newly diagnosed acute myeloid leukemia: long term follow-up from a phase 1b study
. Am J Hematol
. 2021
;96
(2
):208
–17
. 10.
Bazarbachi
A
. Exciting times ahead for older patients with acute myeloid leukemia: azacitidine and venetoclax followed by allogeneic hematopoietic cell transplantation
. Bone Marrow Transplant
. 2022
;57
(2
):147
–8
. 11.
Dohner
H
, Estey
E
, Grimwade
D
, Amadori
S
, Appelbaum
FR
, Büchner
T
, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel
. Blood
. 2017
;129
(4
):424
–47
. 12.
DiNardo
CD
, Jonas
BA
, Pullarkat
V
, Thirman
MJ
, Garcia
JS
, Wei
AH
, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia
. N Engl J Med
. 2020
;383
(7
):617
–29
. 13.
Cao
JJ
, Pei
RZ
, Lu
Y
, Zheng
ZZ
, Yuan
ZY
, Li
DY
, et al. Fludarabine and antithymocyte globulin-based conditioning regimen combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia and myelodysplastic syndrome
. Curr Res Transl Med
. 2023
;71
(1
):103360
–6
. 14.
Harris
AC
, Young
R
, Devine
S
, Hogan
WJ
, Ayuk
F
, Bunworasate
U
, et al. International, multicenter standardization of acute graft-versus-host disease clinical data collection: a report from the Mount Sinai Acute GVHD International Consortium
. Biol Blood Marrow Transplant
. 2016
;22
(1
):4
–10
. 15.
Jagasia
MH
, Greinix
HT
, Arora
M
, Williams
KM
, Wolff
D
, Cowen
EW
, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 Diagnosis and staging working group report
. Biol Blood Marrow Transplant
. 2015
;21
(3
):389
–401.e1
. 16.
Vasu
S
, Kohlschmidt
J
, Mrozek
K
, Eisfeld
AK
, Nicolet
D
, Sterling
LJ
, et al. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission
. Blood Adv
. 2018
;2
(13
):1645
–50
. 17.
Bewersdorf
JP
, Derkach
A
, Gowda
L
, Menghrajani
K
, DeWolf
S
, Ruiz
JD
, et al. Venetoclax-based combinations in aml and high-risk mds prior to and following allogeneic hematopoietic cell transplant
. Leuk Lymphoma
. 2021
;62
(14
):3394
–401
. 18.
Yang
TT
, Song
XL
, Zhao
YM
, Ye
BD
, Luo
Y
, Xiao
HW
, et al. Outcome after allogeneic hematopoietic stem cell transplantation following Venetoclax-based therapy among AML and MDS patients
. Ann Hematol
. 2022
;101
(12
):2731
–41
. 19.
Sandhu
KS
, Dadwal
S
, Yang
D
, Mei
M
, Palmer
J
, Salhotra
A
, et al. Outcome of allogeneic hematopoietic cell transplantation after venetoclax and hypomethylating agent therapy for acute myelogenous leukemia
. Biol Blood Marrow Transplant
. 2020
;26
(12
):e322
–7
. 20.
Pasvolsky
O
, Shimony
S
, Ram
R
, Shimoni
A
, Shargian
L
, Avni
B
, et al. Allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first complete remission after 5-azacitidine and venetoclax: a multicenter retrospective study
. Ann Hematol
. 2022
;101
(2
):379
–87
. 21.
Mukherjee
A
, Milton
DR
, Jabbour
E
, Daver
N
, Gulbis
A
, Ledesma
C
, et al. Risk of GvHD and survival in patients with acute leukemia who were bridged to allogeneic stem cell transplantation (alloSCT) with venetoclax-based therapy
. Blood
. 2020
;136
(Suppl 1
):13
–4
. 22.
Papaemmanuil
E
, Gerstung
M
, Bullinger
L
, Gaidzik
VI
, Paschka
P
, Roberts
ND
, et al. Genomic classification and prognosis in acute myeloid leukemia
. N Engl J Med
. 2016
;374
(23
):2209
–21
. 23.
Lagunas-Rangel
FA
, Chavez-Valencia
V
, Gomez-Guijosa
MA
, Cortes-Penagos
C
. Acute myeloid leukemia-genetic alterations and their clinical prognosis
. Int J Hematol Oncol Stem Cell Res
. 2017
;11
(4
):328
–39
.24.
Pollyea
DA
, Winters
A
, McMahon
C
, Schwartz
M
, Jordan
CT
, Rabinovitch
R
, et al. Venetoclax and azacitidine followed by allogeneic transplant results inexcellent outcomes and may improve outcomes versus mainte-nance therapy among newly diagnosed AML patients older than 60
. Bone Marrow Transplant
. 2022
;57
(2
):160
–6
. 25.
Winters
AC
, Bosma
G
, Abbott
D
, Minhajuddin
M
, Jordan
C
, Pollyea
DA
, et al. Outcomes are similar after allogeneic hematopoietic stem cell transplant for newly diagnosed acute myeloid leukemia patients who received venetoclax + azacitidine versus intensive chemotherapy
. Transplant Cell Ther
. 2022
;28
(10
):694.e1
–9
. © 2024 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2024
You do not currently have access to this content.
