2022 SOHO Quizartinib Research Advances in Newly Diagnosed AML Patients: QuANTUM-First Phase III Study Results

FMS-like tyrosine kinase 3 (FLT3) is one of the most common mutations in acute myeloid leukemia (AML), and FLT3 internal tandem repeat (FLT3-ITD+) mutations are associated
with poor prognosis, high recurrence rates, and low overall survival (OS) rates.
Quizartinib is a highly potent, selective second-generation LLL FLT3 inhibitor that has been shown to have clinical efficacy and controlled safety
alone.
The QuANTUM-First study (NCT02668653) is a global, randomized, double-blind, phase III study evaluating the efficacy
of Quizartinib monotherapy (up to 3 years) after standard induction and post-remission consolidation therapy in patients with newly diagnosed FLT3-ITD+ AML.
The results of its study were presented
at the annual meeting of the American Society of Hematology and Oncology (SOHO) this year.

The research methodology is shown in Figure 1
.

Figure 1

Baseline characteristics

539 patients were randomly assigned to either the Quizartinib group (N=268) or placebo group (N=271; Figure 2).

At data cut-off (August 13, 2021), the median follow-up was approximately 39 months
.
Baseline and disease characteristic balance between the two groups of patients (Table 1; Table 2).

The median age of patients in each group was 56 years, and about 40% of patients were ≥ 60 years old
.

Figure 2

Table 1

Table 2

OS results

The addition of Quizartinib had clinically significant and statistically significant improvements in OS compared with standard induction and consolidation therapy alone (HR, 0.
776; 95% CI, 0.
615-0.
979; P=0.
0324; Figure 3).

The median OS in the Quizartinib group was 31.
9 months and 15.
1 months
in the placebo group.

Figure 3

Other efficacy results

No event lifetime (EFS) is not significant, as shown in Table 3
.
The CRc rate in the Quizartinib group (71.
6%) was higher than in the placebo group (64.
9%); However, CR rates were similar between the two groups (54.
9% and 55.
4%, respectively; Table 4) CR duration was 38.
6 months in the Quizartinib group and 12.
4 months in the placebo group (Table 4
).

Table 3

Table 4

security

The incidence of adverse events (TEAE) that occurred during treatment between the two groups was similar to the incidence of ≥grade 3 TEAE (Table 5
).
The most common TEAE is present in patients with newly diagnosed AML who receive intensive chemotherapy (Table 6
).
QT interval prolongation occurred more frequently in the Quizartinib group than in the placebo group, and most cases were mild or moderate, which could be controlled by adjusting the Quizartinib dose and correcting other risk factors (Table 7).

Table 5

Table 6

Table 7

In the key phase III study of QuANTUM-First, the use of Quizartinib in combination with standard induction and consolidation therapy followed by a single agent for 3 years improved the OS of patients aged 18-75 years with a new diagnosis of FLT3-ITD+ AML, and the safety of the study protocol was manageable and no new safety issues emerged
.
These data have the potential to alter the treatment criteria for newly diagnosed adult patients with FLT3-ITD+ AML
.

Reference source: Harry Erba, et al.
2022 SOHO.
AML-029.

Editor: Quinta

Typesetting: Quinta

Execution: moly

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