Venetoclax is safe and tolerable as post-transplant maintenance therapy for AML patients at high risk for relapse

被引:26
作者
Kent, Andrew [1 ]
Schwartz, Marc [1 ]
McMahon, Christine [1 ]
Amaya, Maria [1 ]
Smith, Clayton A. A. [1 ]
Tobin, Jennifer [1 ]
Marciano, Kelsey [1 ]
Rezac, Rebecca [1 ]
Bosma, Grace [1 ]
Pollyea, Daniel A. A. [1 ]
Gutman, Jonathan A. A. [1 ]
机构
[1] Univ Colorado, Sch Med, Div Hematol, Aurora, CO 80045 USA
关键词
ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELL TRANSPLANTATION; BCL-2; INHIBITION; AZACITIDINE; DISEASE; BLOOD; MDS;
D O I
10.1038/s41409-023-01987-5
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Relapse is the most common cause of mortality in acute myeloid leukemia (AML) patients after allogeneic stem cell transplant (SCT). Post-SCT maintenance strategies that prevent relapse are desirable but must be well tolerated and convenient to administer. We hypothesized single agent venetoclax (ven) may be an effective maintenance therapy among high relapse risk patients. Between February 2019 and December 2021, we administered post-SCT ven maintenance to 49 AML patients at high-risk for relapse as a prospectively defined off-label practice at our institution. Ven was planned to be administered until 1-year post-SCT. While temporary interruptions were common (67.3% of all patients), of those with >1 year follow up, 22/25 (88%) completed the full year of planned therapy. Cytopenias (40.8%) and gastrointestinal adverse events (34.7%) were the most common toxicities. At 1-year post-SCT, overall survival (OS) and relapse-free survival (RFS) were 70% and 67% respectively. Our experience demonstrates single agent ven is a safe, tolerable, and feasible maintenance therapy that may improve RFS and OS in high relapse risk post-SCT patients.
引用
收藏
页码:849 / 854
页数:6
相关论文
共 42 条
[1]   Evaluation of Trends and Prognosis Over Time in Patients with AML Relapsing After Allogeneic Hematopoietic Cell Transplant Reveals Improved Survival for Young Patients in Recent Years [J].
Bazarbachi, Ali ;
Schmid, Christoph ;
Labopin, Myriam ;
Beelen, Dietrich ;
Blau, Igor Wolfgang ;
Potter, Victoria ;
Niittyvuopio, Riitta ;
Socie, Gerard ;
Blaise, Didier ;
Sanz, Jaime ;
Ciceri, Fabio ;
Abou Dalle, Iman ;
Spyridonidis, Alexandros ;
Bug, Gesine ;
Esteve, Jordi ;
Savani, Bipin N. ;
Nagler, Arnon ;
Mohty, Mohamad .
CLINICAL CANCER RESEARCH, 2020, 26 (24) :6475-6482
[2]   Survival of Patients with Acute Myeloid Leukemia Relapsing after Allogeneic Hematopoietic Cell Transplantation: A Center for International Blood and Marrow Transplant Research Study [J].
Bejanyan, Nelli ;
Weisdorf, Daniel J. ;
Logan, Brent R. ;
Wang, Hai-Lin ;
Devine, Steven M. ;
de Lima, Marcos ;
Bunjes, Donald W. ;
Zhang, Mei-Jie .
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2015, 21 (03) :454-459
[3]   Hypomethylating Agents and FLT3 Inhibitors As Maintenance Treatment for Acute Myeloid Leukemia and Myelodysplastic Syndrome After Allogeneic Hematopoietic Stem Cell Transplantation-A Systematic Review and Meta-Analysis [J].
Bewersdorf, Jan Philipp ;
Allen, Cecily ;
Mirza, Abu-Sayeef ;
Grimshaw, Alyssa A. ;
Giri, Smith ;
Podoltsev, Nikolai A. ;
Gowda, Lohith ;
Cho, Christina ;
Tallman, Martin S. ;
Zeidan, Amer M. ;
Stahl, Maximilian .
TRANSPLANTATION AND CELLULAR THERAPY, 2021, 27 (12) :997.e1-997.e11
[4]   Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial) [J].
Bug, G. ;
Burchert, A. ;
Wagner, E-M ;
Kroeger, N. ;
Berg, T. ;
Gueller, S. ;
Metzelder, S. K. ;
Wolf, A. ;
Huenecke, S. ;
Bader, P. ;
Schetelig, J. ;
Serve, H. ;
Ottmann, O. G. .
LEUKEMIA, 2017, 31 (11) :2523-2525
[5]   Sorafenib Maintenance After Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia With FLT3-Internal Tandem Duplication Mutation (SORMAIN) [J].
Burchert, Andreas ;
Bug, Gesine ;
Fritz, Lea V. ;
Finke, Juergen ;
Stelljes, Matthias ;
Roellig, Christoph ;
Wollmer, Ellen ;
Waesch, Ralph ;
Bornhaeuser, Martin ;
Berg, Tobias ;
Lang, Fabian ;
Ehninger, Gerhard ;
Serve, Hubert ;
Zeiser, Robert ;
Wagner, Eva-Maria ;
Kroeger, Nicolaus ;
Wolschke, Christine ;
Schleuning, Michael ;
Goetze, Katharina S. ;
Schmid, Christoph ;
Crysandt, Martina ;
Esseling, Eva ;
Wolf, Dominik ;
Wang, Ying ;
Boehm, Alexandra ;
Thiede, Christian ;
Haferlach, Torsten ;
Michel, Christian ;
Bethge, Wolfgang ;
Wuendisch, Thomas ;
Brandts, Christian ;
Harnisch, Susanne ;
Wittenberg, Michael ;
Hoeffkes, Heinz-Gert ;
Rospleszcz, Susanne ;
Burchardt, Alexander ;
Neubauer, Andreas ;
Brugger, Markus ;
Strauch, Konstantin ;
Schade-Brittinger, Carmen ;
Metzelder, Stephan K. .
JOURNAL OF CLINICAL ONCOLOGY, 2020, 38 (26) :2993-3002
[6]   Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia [J].
Cherry, Evan M. ;
Abbott, Diana ;
Amaya, Maria ;
McMahon, Christine ;
Schwartz, Marc ;
Rosser, Julie ;
Sato, Audrey ;
Schowinsky, Jeffrey ;
Inguva, Anagha ;
Minhajuddin, Mohd ;
Pei, Shanshan ;
Stevens, Brett ;
Winters, Amanda ;
Jordan, Craig T. ;
Smith, Clayton ;
Gutman, Jonathan A. ;
Pollyea, Daniel A. .
BLOOD ADVANCES, 2021, 5 (24) :5565-5573
[7]   Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel [J].
Doehner, Hartmut ;
Estey, Elihu ;
Grimwade, David ;
Amadori, Sergio ;
Appelbaum, Frederick R. ;
Buechner, Thomas ;
Dombret, Herve ;
Ebert, Benjamin L. ;
Fenaux, Pierre ;
Larson, Richard A. ;
Levine, Ross L. ;
Lo-Coco, Francesco ;
Naoe, Tomoki ;
Niederwieser, Dietger ;
Ossenkoppele, Gert J. ;
Sanz, Miguel ;
Sierra, Jorge ;
Tallman, Martin S. ;
Tien, Hwei-Fang ;
Wei, Andrew H. ;
Lowenberg, Bob ;
Bloomfield, Clara D. .
BLOOD, 2017, 129 (04) :424-447
[8]   Enasidenib as maintenance following allogeneic hematopoietic cell transplantation for IDH2-mutated myeloid malignancies [J].
Fathi, Amir T. ;
Kim, Haesook T. ;
Soiffer, Robert J. ;
Levis, Mark J. ;
Li, Shuli ;
Kim, Annette S. ;
Mims, Alice S. ;
DeFilipp, Zachariah ;
El-Jawahri, Areej ;
McAfee, Steven L. ;
Brunner, Andrew M. ;
Narayan, Rupa ;
Knight, Laura W. ;
Kelley, Devon ;
Bottoms, Aj S. ;
Perry, Lindsey H. ;
Wahl, Jonathan L. ;
Brock, Jennifer ;
Breton, Elayne ;
Ho, Vincent T. ;
Chen, Yi-Bin .
BLOOD ADVANCES, 2022, 6 (22) :5857-5865
[9]   Acute myeloblastic leukaemias and myelodysplastic syndromes in adult patients: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].
Fey, M. F. ;
Dreyling, M. .
ANNALS OF ONCOLOGY, 2010, 21 :v158-v161
[10]   Chronic graft versus host disease burden and late transplant complications are lower following adult double cord blood versus matched unrelated donor peripheral blood transplantation [J].
Gutman, J. A. ;
Ross, K. ;
Smith, C. ;
Myint, H. ;
Lee, C-K ;
Salit, R. ;
Milano, F. ;
Delaney, C. ;
Gao, D. ;
Pollyea, D. A. .
BONE MARROW TRANSPLANTATION, 2016, 51 (12) :1588-1593