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<p>Menin inhibition leads to an antileukemic effect through hematopoietic differentiation. Treatment with the menin inhibitor revumenib results in clinical remissions in relapsed or refractory (R/R) acute myeloid leukemia (AML) with either rearrangement of lysine methyltransferase&#xa0;2A (<i>KMT2A</i>) or mutation in nucleophosmin 1 (<i>NPM1</i>), leading to regulatory approval of this drug. However, determinants of response to revumenib have not been fully elucidated. We examined the immunophenotype of leukemia cells by flow cytometry, in sequential bone marrow specimens from 48 patients with R/R AML treated with revumenib. We observed dynamic changes in the immunophenotype after treatment in 16 of 31 (52%) patients, characterized by a switch from a myeloid/stem-like to a monocytic or myelomonocytic immunophenotype, or vice versa, or by substantial changes in the intensity of antigen expression or in patterns of leukemia-associated immunophenotypes. Morphologic remission with undetectable measurable residual disease (MRD) by flow cytometry following revumenib was associated with improved overall survival, with a median of 23.6 months compared with 20.8 months in patients with morphologic response and detectable MRD, and 3.2 months in non-responders. In summary, treatment monitoring of AML by flow cytometry, following menin inhibition, requires recognition of phenotypic changes associated with differentiation.</p>

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Immunophenotypic changes following menin inhibition in acute myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月11日

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  • Sanam Loghavi,
  • Aziz Farhat,
  • Trevor J. Jamison,
  • Georgina El Hajjar,
  • Alex Bataller,
  • Sa A. Wang,
  • Wei Wang,
  • Guilin Tang,
  • Andres E. Quesada,
  • Alexandre Bazinet,
  • Branko Cuglievan,
  • Courtney D. DiNardo,
  • Guillermo Montalban-Bravo,
  • Koichi Takahashi,
  • Nicholas J. Short,
  • Hussein A. Abbas,
  • Tapan Kadia,
  • Farhad Ravandi,
  • Naval Daver,
  • Elias Jabbour,
  • Gautam Borthakur,
  • Michael Andreeff,
  • L. Jeffrey Medeiros,
  • Hagop M. Kantarjian,
  • Ghayas C. Issa

摘要

Menin inhibition leads to an antileukemic effect through hematopoietic differentiation. Treatment with the menin inhibitor revumenib results in clinical remissions in relapsed or refractory (R/R) acute myeloid leukemia (AML) with either rearrangement of lysine methyltransferase 2A (KMT2A) or mutation in nucleophosmin 1 (NPM1), leading to regulatory approval of this drug. However, determinants of response to revumenib have not been fully elucidated. We examined the immunophenotype of leukemia cells by flow cytometry, in sequential bone marrow specimens from 48 patients with R/R AML treated with revumenib. We observed dynamic changes in the immunophenotype after treatment in 16 of 31 (52%) patients, characterized by a switch from a myeloid/stem-like to a monocytic or myelomonocytic immunophenotype, or vice versa, or by substantial changes in the intensity of antigen expression or in patterns of leukemia-associated immunophenotypes. Morphologic remission with undetectable measurable residual disease (MRD) by flow cytometry following revumenib was associated with improved overall survival, with a median of 23.6 months compared with 20.8 months in patients with morphologic response and detectable MRD, and 3.2 months in non-responders. In summary, treatment monitoring of AML by flow cytometry, following menin inhibition, requires recognition of phenotypic changes associated with differentiation.