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

Author(s)

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

Publication Date

2024-03-01

Abstract

PURPOSE: 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. METHODS: Patients with either MRD (≥1 log(10) 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. RESULTS: 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% v 4%; P = .02) and infections (36% v 8%; P = .03), whereas grade 4 neutropenia (32 v 23%) or thrombocytopenia (27 v 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant NPM1 (77%), CBFB::MYH11 (4%), RUNX1::RUNX1T1 (4%), or KMT2A::MLLT3 (4%). Three patients with a log(10) rise in IDH1/2 (12%) were included. By cycle 2 in the MRD relapse cohort, a log(10) 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. CONCLUSION: For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.

Citation

J Clin Oncol . 2024 Mar 1:JCO2301599. doi: 10.1200/JCO.23.01599. Online ahead of print.

Pubmed ID

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

Link

https://hdl.handle.net/10137/12672

Title

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

Type of document

Journal Article

Entity Type

Publication

Author(s)	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
Publication Date	2024-03-01
Abstract	PURPOSE: 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. METHODS: Patients with either MRD (≥1 log(10) 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. RESULTS: 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% v 4%; P = .02) and infections (36% v 8%; P = .03), whereas grade 4 neutropenia (32 v 23%) or thrombocytopenia (27 v 15%) were comparable with the MRD relapse cohort. Markers of molecular MRD relapse included mutant NPM1 (77%), CBFB::MYH11 (4%), RUNX1::RUNX1T1 (4%), or KMT2A::MLLT3 (4%). Three patients with a log(10) rise in IDH1/2 (12%) were included. By cycle 2 in the MRD relapse cohort, a log(10) 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. CONCLUSION: For AML in first remission and either MRD or oligoblastic relapse, venetoclax plus LDAC is well tolerated and highly effective.
Citation	J Clin Oncol . 2024 Mar 1:JCO2301599. doi: 10.1200/JCO.23.01599. Online ahead of print.
Pubmed ID	https://pubmed.ncbi.nlm.nih.gov/38427924/?otool=iaurydwlib
Link	https://hdl.handle.net/10137/12672
Title	Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC).
Type of document	Journal Article
Entity Type	Publication

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

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