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Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based non-intensive therapy
Othman, J. Tiong, I. S. O'Nions, J. Dennis, Michael Mokretar, K. Ivey, A. Austin, M. J. Latif, A. L. Amer, M. Chan, W. Y.
Othman, J.
Tiong, I. S.
O'Nions, J.
Dennis, Michael
Mokretar, K.
Ivey, A.
Austin, M. J.
Latif, A. L.
Amer, M.
Chan, W. Y.
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Abstract
Assessment of measurable residual disease (MRD) by RT-qPCR is strongly prognostic in patients with NPM1-mutated AML treated with intensive chemotherapy, however there are no data regarding its utility in venetoclax-based non-intensive therapy, despite high efficacy in this genotype. We analysed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved CR/CRi following treatment with venetoclax and hypomethylating agents (HMA) or low dose cytarabine (LDAC). 44 patients (58%) achieved bone marrow (BM) MRD negativity and a further 14 (18%) a reduction of ≥4 log10 from baseline as their best response, with no difference between HMA and LDAC. The cumulative rate of BM MRD negativity by the end of cycles 2, 4 and 6 was 25%, 47% and 50%. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall (OS) of 84% compared to 46% if MRD positive. On multivariable analyses MRD negativity was the strongest prognostic factor. 22 patients electively stopped therapy in BM MRD negative remission after a median of 8 cycles with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.
Authors
Othman, J.
Tiong, I. S.
O'Nions, J.
Dennis, Michael
Mokretar, K.
Ivey, A.
Austin, M. J.
Latif, A. L.
Amer, M.
Chan, W. Y.
Crawley, C. R.
Crolla, F.
Cross, J. W.
Dang, R.
Elliot, Johnathon
Fong, C. Y.
Galli, S.
Gallipoli, P.
Hogan, F.
Kalkur, P.
Khan, A. B.
Krishnamurthy, P.
Laurie, J.
Loo, S.
Marshall, S.
Mehta, P.
Murthy, V.
Nagumantry, S.
Pillai, S.
Potter, N.
Sellar, R. S.
Taylor, T.
Zhao, R.
Russell, N. H.
Wei, A. H.
Dillon, R.
Tiong, I. S.
O'Nions, J.
Dennis, Michael
Mokretar, K.
Ivey, A.
Austin, M. J.
Latif, A. L.
Amer, M.
Chan, W. Y.
Crawley, C. R.
Crolla, F.
Cross, J. W.
Dang, R.
Elliot, Johnathon
Fong, C. Y.
Galli, S.
Gallipoli, P.
Hogan, F.
Kalkur, P.
Khan, A. B.
Krishnamurthy, P.
Laurie, J.
Loo, S.
Marshall, S.
Mehta, P.
Murthy, V.
Nagumantry, S.
Pillai, S.
Potter, N.
Sellar, R. S.
Taylor, T.
Zhao, R.
Russell, N. H.
Wei, A. H.
Dillon, R.
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Date
2023
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Article
Citation
Othman J, Tiong IS, O'Nions J, Dennis M, Mokretar K, Ivey A, et al. Molecular MRD is strongly prognostic in patients with NPM1-mutated AML receiving venetoclax-based non-intensive therapy. Blood. 2023 Aug 30. PubMed PMID: 37647641. Epub 2023/08/30. eng.