Melissa Badamo

Blood Cancers Today

Researchers have validated a new molecular prognostic risk signature (mPRS) for patients with acute myeloid leukemia (AML) who received hypomethylating agents (HMAs) and venetoclax, according to a single-center, retrospective study published in Blood Advances.
“HMAs and venetoclax represent the standard of care for patients with AML who are ineligible for intensive chemotherapy,” wrote Alex Bataller, MD, PhD, of The University of Texas MD Anderson Cancer Center in Houston, and colleagues. “However, the European LeukemiaNet (ELN) risk classifications have been validated for patients treated with intensive therapy.”
The mPRS was developed using data from the phase III VIALE-A trial of patients who received azacitidine and venetoclax. The classification uses a four-gene approach (NRAS, KRAS, FLT3-internal tandem duplication, or TP53 mutations) to stratify patients into three groups: the higher-benefit group, the intermediate-benefit group, and the lower-benefit group.
Using data from 159 patients, the researchers compared the overall response rate (ORR), median overall survival (OS), event-free survival (EFS), and two-year cumulative incidence of relapse (CIR) for each benefit group (See TABLE 1).
TABLE 1: Responses for each benefit group
<table>
<tbody>
<tr>
<td width="125">Benefit Group</td>
<td width="125">ORR</td>
<td width="125">OS</td>
<td width="125">EFS</td>
<td width="125">Two-Year CIR</td>
</tr>
<tr>
<td width="125">Higher-benefit group</td>
<td width="125">86%</td>
<td width="125">30 months</td>
<td width="125">19 months</td>
<td width="125">35%</td>
</tr>
<tr>
<td width="125">Intermediate-benefit group</td>
<td width="125">54%</td>
<td width="125">12 months</td>
<td width="125">8 months</td>
<td width="125">70%</td>
</tr>
<tr>
<td width="125">Lower-benefit group</td>
<td width="125">59%</td>
<td width="125">5 months</td>
<td width="125">4 months</td>
<td width="125">60%</td>
</tr>
</tbody>
</table>
&nbsp;
The researchers also compared baseline characteristics among the three groups. Patients in the intermediate- and lower-benefit groups had lower hemoglobin levels and platelet counts than those in the higher-benefit group. Patients in the lower-benefit group had lower incidence of NPM1 (2%), ASXL1 (7%), RUNX1 (6%), and IDH1/2 (6%) mutations than those in the higher- and intermediate-groups (P&lt;.05). The incidence of therapy-related neoplasms was higher in the lower-benefit group (32%) than the higher- (18%) and intermediate-benefit (10%) groups (P=.038).
NRAS, KRAS, and TP53 mutations also negatively affected patient outcomes, the researchers noted. Therefore, new treatment approaches are necessary.
“When compared with the ELN22 system, [the] mPRS classification performs better in predicting survival,” Dr. Bataller and colleagues concluded. “A larger study including cooperative groups or a multi-institutional study would be necessary to support our data.”
Reference
Bataller A, Bazinet A, DiNardo CD, et al. Prognostic risk signature in patients with acute myeloid leukemia treated with hypomethylating agents and venetoclax. Blood Adv 2024;8(4):927–935. doi: 10.1182/bloodadvances.2023011757

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