VIALE-A trial: Long-term efficacy and safety follow-up

The combination of venetoclax (Ven) + azacitidine (Aza) was approved in 2018 for the treatment of patients with newly diagnosed acute myeloid leukemia, aged ≥75 years old, or ineligible for intensive chemotherapy. The phase III VIALE-A trial (NCT02993523) evaluating Ven + Aza vs placebo + Aza met its primary endpoint of improved overall survival (OS).

Recently, Pratz et al.¹ published a long-term efficacy and safety follow-up of the VIALE-A trial in American Journal of Hematology. We summarize the key results below.

Study design¹

• The VIALE-A trial was a multicenter, randomized, placebo-controlled, double-blind study.
• Patients were randomized 2:1 to receive Ven + Aza or placebo + Aza.
• The primary endpoint of the long-term follow-up was OS.

Key findings¹

• N = 431 (intent-to-treat population)
  • N = 286 (Ven + Aza)
  • n = 145 (placebo + Aza)
• The median follow-up was 43.2 months.
• The median OS across patient subgroups was superior for Ven + Aza vs placebo + Aza (Figure 1).

Aza, azacitidine; OS, overall survival; Ven, venetoclax.
^*Adapted from Pratz et al.^1
†Ven + Aza (n = 61), placebo + Aza (n = 28).
^‡Ven + Aza (n = 23), placebo + Aza (n = 11).
^§Ven + Aza (n = 40), placebo + Aza (n = 18).

• The estimated 24-month OS rate for Ven + Aza was 37.5% vs 16.9% for placebo + Aza.
• The complete response (CR) rate for patients treated with Ven + Aza was 38.8% vs 17.9% for placebo + Aza (p < 0.001).
• The rate of CR/CR with incomplete count recovery in patients treated with Ven + Aza was 66.8% vs 29% for placebo + Aza (p < 0.001).
• Any-grade hematologic and gastrointestinal treatment-emergent adverse events were more frequent in patients treated with Ven + Aza (n = 283) vs placebo + Aza (n =144) (Table 1).

Table 1. Any-grade hematologic and GI TEAEs in ≥20% of patients*

AE, adverse event; AZA, azacitidine; GI, gastrointestinal; TEAE, treatment-emergent adverse event; VEN, venetoclax. *Adapted from Pratz, et al.1
TEAE (%)	Ven + Aza (n = 283)	Placebo + Aza (n = 144)
Hematologic AE
Thrombocytopenia	47	42
Febrile neutropenia	43	19
Neutropenia	43	29
Anemia	31	23
Leukopenia	21	14
GI AE
Diarrhea	45	34
Nausea	45	37
Constipation	44	40
Vomiting	30	24

• Treatment discontinuations due to treatment-emergent adverse events occurred in 30% of patients treated with Ven + Aza vs 22% for placebo + Aza.

Key learnings

The additional 2-year follow-up highlighted a longer median OS, reduced risk of death, and higher CR rates in patients treated with Ven + Aza vs placebo + Aza. This clinical benefit was also sustained across the patient subgroups. Overall, the combination of Ven + Aza supports the need for effective treatment in older patients who are ineligible for intensive chemotherapy and otherwise have limited therapeutic choices.