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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Date
2024
Authors
Tiong, I.S.
Hiwase, D.K.
Abro, E.
Bajel, A.
Palfreyman, E.
Beligaswatte, A.
Reynolds, J.
Anstee, N.
Nguyen, T.
Loo, S.
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Journal of Clinical Oncology, 2024; 42(18):2161-2173
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Ing Soo Tiong, Devendra K. Hiwase, Emad Abro, Ashish Bajel, Emma Palfreyman, Ashanka Beligaswatte, John Reynolds, Natasha Anstee, Tamia Nguyen, Sun Loo, Chong Chyn Chua, Michael Ashby, Kaitlyn M. Wiltshire, Shaun Fleming, Chun Y. Fong, Tse-Chieh Teh, Piers Blombery, Richard Dillon, Adam Ivey, and Andrew H. Wei
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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 log10 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 5 26) or oligoblastic (n 5 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 5 .02) and infections (36% v 8%; P 5 .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 log10 rise in IDH1/2 (12%) were included. By cycle 2 in the MRD relapse cohort, a log10 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.
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© 2024 by American Society of Clinical Oncology. Open Access Creative Commons Attribution Non-Commercial No Derivatives 4.0 License