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2024-03-18T16:05:57.000Z

Real-world study of HMA + Ven in older patients with newly diagnosed AML

Mar 18, 2024
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Learning objective: After reading this article, learners will be able to cite a new development in the treatment of acute myeloid leukemia.

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Hypomethylating agents (HMA) + venetoclax (Ven) is the current standard of care for patients with newly diagnosed acute myeloid leukemia aged ≥75 years old or who are ineligible for intensive chemotherapy. This consensus is based on results obtained from a phase Ib trial (NCT02203773) and the phase III VIALE-A trial (NCT02993523).1 However, even though it is low intensity, the regimen places a significant burden on patients due to myelosuppression, bone marrow assessments, and an indefinite treatment period.1

Here, we summarize a real-world study published by Abaza et al.1 in American Journal of Hematology on efficacy, safety, and survival outcomes of HMA + Ven in elderly patients with newly diagnosed acute myeloid leukemia.

Study design

  • This multicenter retrospective study, enrolled patients treated between 2017 and 2022.1
  • Patients were risk stratified using the European LeukemiaNet 2022 system and the recently proposed 4-gene prognostic model2
    • The genes assessed in the proposed model were TP53, FLT3-ITD, NRAS, and KRAS1

Key findings1

  • A total of 204 patients with response assessment available for 167.
  • The median follow-up was 8 months.
  • The complete response (CR) rate and CR with incomplete count recovery (CRi) rate for the overall population were 38% and 26%, respectively.
  • The median duration of response was 14.2 months, and the median overall survival (OS) was 9.5 months.
  • The CR/CRi rate and median overall survival were superior in the European LeukemiaNet favorable-risk group and higher risk-benefit group from the 4-gene prognostic model (Figure 1).

Figure 1. A ELN risk stratified CR/CRi rate, B 4-gene prognostic model stratified CR/CRi rate, C ELN risk stratified median OS, and D 4-gene prognostic model stratified median OS* 

CR, complete response; CRi, CR with incomplete count recovery; ELN, European LeukemiaNet; OS, overall survival.
*Adapted from Abaza, et al.1

  • Among responders, relapse after treatment occurred in 59% of patients.
    • The median time to relapse was 7.2 months.
  • Patients with a TP53 mutation had poorer OS compared with wild-type (median, 2.5 months vs 13.3 months; p < 0.0001).
  • The median overall survival was significantly longer in patients with NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively; p < 0.0001).
  • Treatment interruption was required in 79% of patients, while 74% of patients required a dose reduction.
  • In total, 72% of patients died.
  • The 30-day and 60-day mortality rates were 9% and 19%, respectively.
  • The most common causes of early mortality were:
    • infection (42%);
    • disease progression (17%); and
    • bleeding (11%).

Key learnings

  • Good responses to HMA + Ven were reported in this real-world clinical setting; however, the survival was poorer than reported in the VIALE-A trial.
  • Patients who do not yield a desired response with HMA + Ven still respond poorly to salvage therapy with limited OS and is a key area of unmet clinical need.
  • Overall, HMA + Ven remains an effective treatment option for older patients and is now under evaluation for younger patients in a randomized, multicenter trial comparing conventional chemotherapy to Ven + azacitidine (NCT04801797).

  1. Abaza Y, Winer E, Murthy G, et al. Clinical outcomes of hypomethylating agents plus venetoclax as frontline treatment in patients 75 years and older with acute myeloid leukemia: Real-world data from eight US academic centers. Am J of Hematol. 2024. Online ahead of print. DOI: 1002/ajh.27231
  2. Döhner H, Pratz K, DiNardo C, et al. ELN risk stratification is not predictive of outcomes for treatment-naïve patients with acute myeloid leukemia treated with venetoclax and azacitidine. Blood. 2022;140(Suppl.1):1441-1444. DOI: 1182/blood-2022-169509

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