Tiong, Ing Soo

Hiwase, Devendra K

Abro, Emad

Bajel, Ashish

Palfreyman, Emma

Beligaswatte, Ashanka

Reynolds, John

Anstee, Natasha

Nguyen, Tamia

Loo, Sun

Chua, Chong Chyn

Ashby, Michael

Wiltshire, Kaitlyn M

Fleming, Shaun

Fong, Chun Y

Teh, Tse-Chieh

Blombery, Piers

Dillon, Richard

Ivey, Adam

Wei, Andrew H

2024-06-20

A prospective phase II study examined the safety and efficacy of venetoclax combined with low-dose cytarabine (LDAC) in AML at first measurable residual disease (MRD) or oligoblastic relapse.Patients with either MRD (≥1 log rise) or oligoblastic relapse (blasts 5%-15%) received venetoclax 600 mg once daily D1-28 plus LDAC once daily D1-10 in 28-day cycles. The primary objective was MRD response in the MRD relapse cohort or complete remission (CR/CRh/CRi) in the oligoblastic relapse cohort.Forty-eight adults with either MRD (n = 26) or oligoblastic (n = 22) relapse were enrolled. Median age was 67 years (range, 18-80) and 94% had received previous intensive chemotherapy. Patients received a median of four cycles of therapy; 17% completed ≥12 cycles. Patients with oligoblastic relapse had more grade ≥3 anemia (32% 4%; = .02) and infections (36% 8%; = .03), whereas grade 4 neutropenia (32 23%) or thrombocytopenia (27 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant (77%), (4%), (4%), or (4%). Three patients with a log rise in / (12%) were included. By cycle 2 in the MRD relapse cohort, a log reduction in MRD was observed in 69%; 46% achieved MRD negative remission. In the oligoblastic relapse cohort, 73% achieved CR/CRh/CRi. Overall, 21 (44%) underwent hematopoietic cell transplantation. Median overall survival (OS) was not reached in either cohort. Estimated 2-year OS rate was 67% (95% CI, 50 to 89) in the MRD and 53% (95% CI, 34 to 84) in the oligoblastic relapse cohorts.For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.

The Alfred Hospital and Monash University, Melbourne, Australia.

Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia.

Royal Adelaide Hospital, Adelaide, Australia.

University of Adelaide, Adelaide, Australia.

South Australian Health and Medical Research Institute, Adelaide, Australia.

Princess Alexandra Hospital, Queensland, Australia.

Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia.

The University of Melbourne, Melbourne, Australia.

Royal Darwin Hospital, Northern Territory, Australia.

University of Adelaide, Adelaide, Australia.

Flinders Medical Centre, Bedford Park, Australia.

The Alfred Hospital and Monash University, Melbourne, Australia.

The University of Melbourne, Melbourne, Australia.

Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia.

The University of Melbourne, Melbourne, Australia.

Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia.

The University of Melbourne, Melbourne, Australia.

Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

The Northern Hospital, Melbourne, Australia.

The Alfred Hospital and Monash University, Melbourne, Australia.

The University of Melbourne, Melbourne, Australia.

Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

The Northern Hospital, Melbourne, Australia.

The Alfred Hospital and Monash University, Melbourne, Australia.

The Alfred Hospital and Monash University, Melbourne, Australia.

The Alfred Hospital and Monash University, Melbourne, Australia.

Austin Health and Olivia Newton John Cancer Research Institute, Melbourne, Australia.

The Alfred Hospital and Monash University, Melbourne, Australia.

Box Hill Hospital, Melbourne, Australia.

Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.

Department of Medical and Molecular Genetics, King's College, London, United Kingdom.

Guy's Hospital, London, United Kingdom.

The Alfred Hospital and Monash University, Melbourne, Australia.

Peter MacCallum Cancer Centre and The Royal Melbourne Hospital, Melbourne, Australia.

The University of Melbourne, Melbourne, Australia.

Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.

J Clin Oncol . 2024 Jun 20;42(18):2161-2173. doi: 10.1200/JCO.23.01599. Epub 2024 Mar 1.

1527-7755

0000-0001-7417-4343

0000-0002-3755-7334

0000-0002-8825-8625

0000-0003-2093-1403

0000-0001-6294-2691

0000-0002-2162-3288

0000-0001-8653-4844

0000-0001-5773-103X

0000-0001-9333-5296

0000-0002-7514-3298

https://pubmed.ncbi.nlm.nih.gov/38427924/?otool=iaurydwlib

https://hdl.handle.net/10137/13407

Humans

Aged

Middle Aged

Leukemia, Myeloid, Acute

Neoplasm, Residual

Cytarabine

Sulfonamides

Adult

Female

Male

Bridged Bicyclo Compounds, Heterocyclic

Antineoplastic Combined Chemotherapy Protocols

Aged, 80 and over

Prospective Studies

Nucleophosmin

Young Adult

Adolescent

Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC).

Journal Article

Publication