Oral decitabine and cedazuridine + venetoclax for the treatment of older patients with newly diagnosed AML

Older patients aged ≥60 years with acute myeloid leukemia (AML) are often not eligible for standard chemotherapy regimens due to adverse risk disease features.¹ However, for this patient population, low-intensity regimens compare favorably with intensive chemotherapy.¹ One promising low-intensity regimen is the oral decitabine and cedazuridine (ASTX727) + venetoclax.

Recently, Bazinet et al.¹ published results from a study (NCT04746235) evaluating the safety and efficacy of ASTX727 + venetoclax in older patients with newly diagnosed AML (ND AML) or with relapsed/refractory AML (R/R AML) in the Lancet Hematology. Here, we summarrize the key results.

Study design¹

• This is an ongoing single-center, phase II study.
• Treatment cycles were 28 days long for up to 24 cycles
  • ASTX727 (cedazuridine 100 mg and decitabine 35 mg) was administered orally on Days 1–5
  • Venetoclax 400 mg was administered orally from Days 21–28
• The primary endpoint was the overall response rate.
• Secondary endpoints were overall survival, relapse-free survival, duration of response, and safety.

Key findings¹

• A total of 62 patients were included, 49 with ND AML and 13 with R/R AML.
• The median follow-up period was 18.3 months.
• The response rates for both patient groups are shown in Figure 1.

CR, complete remission; CRi, CR with incomplete count recovery; ND AML, newly diagnosed acute myeloid leukemia; ORR, overall response rate; R/R AML, relapsed/refractory acute myeloid leukemia.
*Adapted from Bazinet, et al.¹

 

• Of the evaluable patients, negative measurable residual disease was achieved by 44% of patients with ND AML vs 20% with R/R AML.
• The secondary survival endpoints are shown in Table 1.

Table 1. Secondary survival endpoints for patients with ND AML or R/R AML treated with ASTX727 + venetoclax*

Secondary survival endpoints	ND AML (n = 47)	R/R AML (n = 13)
Median OS, months	11.5	7.2
1-year OS, %	49.0	18.0
2-year OS, %	18.0	18.0
Median RFS, months	12.0	4.6
1-year RFS, %	47.0	17.0
Median DOR, months	13.2	5.4
1-year DOR, %	51.0	25.0
AML, acute myeloid leukemia; DOR, duration of response; ND, newly diagnosed; OS, overall survival; RFS, relapse free survival; R/R, relapsed/refractory. *Data from Bazinet, et al.1

• Overall, 82% of patients experienced any-grade treatment-emergent adverse events (TEAEs). The most common were:
  • constipation (23%);
  • oral mucositis (23%); and
  • febrile neutropenia (18%).
• Overall, 63% of patients experienced a Grade ≥3 TEAEs. The most common were:
  • febrile neutropenia (18%);
  • pneumonia (13%); and
  • Respiratory failure (8%).
• There were four fatal TEAEs.

Key learnings

Oral decitabine and cedazuridine (ASTX727) + venetoclax is effective and well tolerated in inducing remissions in older patients with newly diagnosed or R/R AML. The efficacy and safety profile of ASTX727 is comparable with other venetoclax-based regimens. The main advantage of ASTX727 is the oral formulation with the potential to be given in an outpatient setting. The results need to be confirmed in larger phase III multicenter studies.