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

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).

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).