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Cited by 507

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia

Open access
Issa, Ghayas C., Aldoss, Ibrahim, DiPersio, John, Cuglievan, Branko, Stone, Richard, Arellano, Martha, Thirman, Michael J., Patel, Manish R., Dickens, David S., Shenoy, Shalini, Shukla, Neerav, Kantarjian, Hagop, Armstrong, Scott A., Perner, Florian, Perry, Jennifer A., Rosen, Galit, Bagley, Rebecca G., Meyers, Michael L., Ordentlich, Peter, Gu, Yu, Kumar, Vinit, Smith, Steven, McGeehan, Gerard M., Stein, Eytan M.·2023·Nature
DOI 10.1038/s41586-023-05812-3
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Abstract

Targeting critical epigenetic regulators reverses aberrant transcription in cancer, thereby restoring normal tissue function 1–3. The interaction of menin with lysine methyltransferase 2A (KMT2A), an epigenetic regulator, is a dependence in acute leukaemia caused by either rearrangement of KMT2A or mutation of the nucleophosmin 1 gene (NPM1)4–6. KMT2A rearrangements occur in up to 10% of acute leukaemias and have an adverse prognosis, whereas NPM1 mutations occur in up to 30%, forming the most common genetic alteration in acute myeloid leukaemia 7,8. Here, we describe the results of the first-in-human phase 1 clinical trial investigating revumenib (SNDX-5613), a potent and selective oral inhibitor of the menin–KMT2A interaction, in patients with relapsed or refractory acute leukaemia (ClinicalTrials.gov, NCT04065399). We show that therapy with revumenib was associated with a low frequency of grade 3 or higher treatment-related adverse events and a 30% rate of complete remission or complete remission with partial haematologic recovery (CR/CRh) in the efficacy analysis population. Asymptomatic prolongation of the QT interval on electrocardiography was identified as the only dose-limiting toxicity. Remissions occurred in leukaemias refractory to multiple previous lines of therapy. We demonstrate clearance of residual disease using sensitive clinical assays and identify hallmarks of differentiation into normal haematopoietic cells, including differentiation syndrome. These data establish menin inhibition as a therapeutic strategy for susceptible acute leukaemia subtypes.

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Metadata

Authors
Issa, G. C., Aldoss, I., DiPersio, J., Cuglievan, B., Stone, R., Arellano, M., Thirman, M. J., Patel, M. R., Dickens, D. S., Shenoy, S., Shukla, N., Kantarjian, H., Armstrong, S. A., Perner, F., Perry, J. A., Rosen, G., Bagley, R. G., Meyers, M. L., Ordentlich, P., Gu, Y., Kumar, V., Smith, S., McGeehan, G. M., & Stein, E. M.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-03-15
Volume
615
Issue
7954
Pages
920-924
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-05812-3
OpenAlex
W4324330071
Cited by
507
References
31
FWCI
90.34
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. https://app.cochat.ai/papers/10.1038/s41586-023-05812-3
The paper
Issa, G. C., Aldoss, I., DiPersio, J., Cuglievan, B., Stone, R., Arellano, M., Thirman, M. J., Patel, M. R., Dickens, D. S., Shenoy, S., Shukla, N., Kantarjian, H., Armstrong, S. A., Perner, F., Perry, J. A., Rosen, G., Bagley, R. G., Meyers, M. L., Ordentlich, P., . . . Stein, E. M. (2023). The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. Nature. https://doi.org/10.1038/s41586-023-05812-3

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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.