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.

Figure 1. Response rates in patients with ND AML or R/R AML treated with ASTX727 + venetoclax* 

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*

• 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.