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<p>Acute myeloid leukemia (AML) with <i>KMT2A</i> rearrangement (<i>KMT2Ar</i>) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in <i>KMT2A</i>. Signaling-related genes (<i>NRAS</i> 30%, <i>KRAS</i> 23% and <i>FLT3</i>-TKD 16%) were the most frequently mutated in patients with <i>KMT2Ar</i> AML. Patients treated with intensive chemotherapy (IT) achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 81%, and when combined with venetoclax, the CR/CRi rate increased to 100%. Patients treated with low intensity treatment (LIT) achieved an CR/CRi rate of 33%, and when combined with venetoclax, the CR/CRi rate was 61%. For patients treated with IT, the 5-year overall survival (OS) and event-free survival (EFS) rates were 66% and 64%, respectively, compared with 7% in those treated with LIT. Thirty-nine patients (57%) underwent allogeneic stem cell transplantation after achieving CR/CRi. For patients treated with LIT, multivariate analysis demonstrated that <i>N/KRAS</i> mutations were predictive for OS (HR 2.93, 95% CI 1.18–7.29, <i>P</i> = 0.021) and EFS (HR 3.51, 95% CI 1.35–9.24, <i>P</i> = 0.01). In summary, outcomes in <i>KMT2Ar</i> AML have improved over years in patients treated with IT, whereas those treated with LIT continue to show poor survival, highlighting the need for novel combinations.</p>

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Characteristics and outcomes of newly diagnosed acute myeloid Leukemia with KMT2A rearrangements

  • 期刊论文

  • 发表日期：

    2025年5月9日

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  • Alex Bataller,
  • Hannah E. Goulart,
  • Ghayas C. Issa,
  • Courtney D. DiNardo,
  • Naval Daver,
  • Tapan Kadia,
  • Alexandre Bazinet,
  • Ian M. Bouligny,
  • Jayastu Senapati,
  • Fadi G. Haddad,
  • Gautam Borthakur,
  • Koji Sasaki,
  • Nicholas J. Short,
  • Musa Yilmaz,
  • Guillermo Montalban-Bravo,
  • Guiling Tang,
  • Sanam Loghavi,
  • Guillermo Garcia-Manero,
  • Farhad Ravandi,
  • Hagop Kantarjian,
  • Elias Jabbour

摘要

Acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar) has poor outcomes. We analyzed 1,611 patients with AML and 4.3% demonstrated rearrangements in KMT2A. Signaling-related genes (NRAS 30%, KRAS 23% and FLT3-TKD 16%) were the most frequently mutated in patients with KMT2Ar AML. Patients treated with intensive chemotherapy (IT) achieved a complete remission (CR)/CR with incomplete blood count recovery (CRi) rate of 81%, and when combined with venetoclax, the CR/CRi rate increased to 100%. Patients treated with low intensity treatment (LIT) achieved an CR/CRi rate of 33%, and when combined with venetoclax, the CR/CRi rate was 61%. For patients treated with IT, the 5-year overall survival (OS) and event-free survival (EFS) rates were 66% and 64%, respectively, compared with 7% in those treated with LIT. Thirty-nine patients (57%) underwent allogeneic stem cell transplantation after achieving CR/CRi. For patients treated with LIT, multivariate analysis demonstrated that N/KRAS mutations were predictive for OS (HR 2.93, 95% CI 1.18–7.29, P = 0.021) and EFS (HR 3.51, 95% CI 1.35–9.24, P = 0.01). In summary, outcomes in KMT2Ar AML have improved over years in patients treated with IT, whereas those treated with LIT continue to show poor survival, highlighting the need for novel combinations.