Venetoclax plus decitabine vs intensive chemotherapy for young patients with ND AML

Venetoclax plus hypomethylating agent treatment is typically recommended for older/unfit patients with acute myeloid leukemia (AML).¹ A previous phase II trial (NCT04752527) suggested that venetoclax plus decitabine (Ven-Dec) may be beneficial in newly diagnosed (ND) young adult patients with European LeukemiaNet (ELN) 2017 adverse risk AML.¹ However, the potential benefit of this combination in ND young adults with ELN 2017 favorable or intermediate risk AML who are fit for intensive chemotherapy is not well characterized.¹

During the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, Lu¹ presented interim results from a phase IIb trial comparing the safety and efficacy of venetoclax plus decitabine vs intensive chemotherapy as induction therapy in ND patients with AML. Below, we summarize the key findings.

Study design¹

• This was a multicenter, randomized, phase IIb trial (NCT05177731).
• The primary endpoint was the rate of composite complete remission (CRc).
• Secondary endpoints included rate of measurable residual disease (defined as <1×10⁻³ by flow cytometry), safety, event-free survival, and overall survival.

Key findings¹

• Overall, 134 patients with ND AML receiving either Ven-Dec (n = 67) or idarubicin and cytarabine (IA-12; n = 67) were included; median age was 45 years and 40 years, respectively.

Response

• CRc rate was significantly higher with Ven-Dec vs IA-12 following the second induction cycle (Figure 1).

CRc, composite complete remission; IA-12, idarubicin and cytarabine; MRD, measurable residual disease; Ven-Dec, venetoclax and decitabine.
*Adapted from Lu.¹

 

• When analyzed by ELN 2017 risk group, the CRc rate after the second induction cycle was significantly higher with Ven-Dec vs IA-12 for patients in the intermediate and adverse risk groups (Figure 2).

CRc, composite complete remission; ELN, European LeukemiaNet; IA-12, idarubicin and cytarabine; MRD, measurable residual disease; Ven-Dec, venetoclax plus decitabine.
*Adapted from Lu.¹

 

• Subgroup analysis of CRc rate after the second induction cycle showed a significant benefit of Ven-Dec vs IA-12 in patients aged ≥40 years (95% vs 69.4%; p = 0.005) and patients with a blast burden of 30–50% (100% vs 68.8%; p = 0.006).

Safety

• Ven-Dec was well tolerated vs IA-12 (Table 1).

Table 1. Safety analysis by treatment received*

IA-12, idarubicin and cytarabine; PLT, platelet; RBC, red blood cell; Ven-Dec, venetoclax plus decitabine. *Adapted from Lu.1
Adverse events, % (unless otherwise specified)	Ven-Dec (n = 67)	IA-12 (n = 67)	p-value
30-day mortality	0	1.5	—
100-day mortality	1.5	4.5	0.362
Fever
Any-grade	53.7	82.1	<0.01
Grade ≥3	9.0	26.9	0.012
Febrile neutropenia
Grade ≥3	37.3	74.6	<0.01
Infection
Grade ≥3	26.8	67.2	<0.01
Sepsis	4.5	29.9	<0.01
Pneumonia	19.4	32.8	0.115
Mean duration of thrombocytopenia, day (range)	12.4 (0–42)	20.2 (4–47)	<0.01
Mean duration of neutropenia, day (range)	22.9 (0–45)	20.8 (1–47)	0.19
Mean RBC transfusion, units (range)	14 (0–44)	17.6 (0–48)	0.05
Mean PLT transfusion, units (range)	46 (0–130)	78 (30–270)	<0.01

Survival

• At a median follow-up of 7.5 months, median overall survival was not reached in either treatment arm, and median event-free survival was not reached in the Ven-Dec arm vs 10.8 months in the IA-12 arm.

Key learnings

Venetoclax plus decitabine was associated with comparable efficacy and was well tolerated when compared with intensive chemotherapy in ND younger patients with AML. Patients aged ≥40 years and with intermediate- or high-risk factors may particularly benefit from this regimen.