ELPIS: Efficacy and safety of aspacytarabine in patients with AML who are ineligible for intensive chemotherapy

The use of high-dose cytarabine in older or ineligible patients with acute myeloid leukemia (AML) is associated with gastrointestinal and cerebellar toxicity. On August 4, 2020, the U.S Food and Drug Administration (FDA) granted aspacytarabine Fast Track designation for the treatment of AML in older patients, and an early phase I/II trial of aspacytarabine, a novel cytarabine, demonstrated its safety in patients with AML.

Here, we summarize a phase II study published by Altman et al.¹ in Blood Advances assessing the efficacy and safety of aspacytarabine in patients with AML.

Study design¹

• This was an open-label, multicenter study (NCT03435848) in previously untreated patients with de novo or secondary AML who are ineligible for intensive chemotherapy.
• Treatment included one or two induction cycles followed by ≤3 cycles of consolidation with aspacytarabine monotherapy at 4.5 g/m²/day, administered intravenously for 6 days.
  • Patients who demonstrated measurable residual disease after the second course were allowed a third cycle of consolidation.
• The primary endpoint was complete remission (CR), compared with age-matched controls from best standard of care at protocol initiation, and the secondary endpoint was the incidence of adverse events (AEs).

Key findings¹

• The CR rates in the intent-to-treat (ITT) population and subgroups are shown in Figure 1
• Overall, the ITT CR rate was higher compared with an age-matched meta-analysis of historical studies of low-dose cytarabine and hypomethylating agents
• At a median follow-up of 13.7 months, 65 and 66 patients were assessed for response and safety, respectively
• In the ITT population (n = 65), overall survival (OS) was 9 months (range, 6–15.9 months)
• In the responder group, OS was not reached (n = 24); 1-year OS was 79.3%
• In the non-responder group, OS was 4 months (range, 2–7.9 months)
• Median relapse-free survival was 8.7 months; 1-year relapse-free survival was 40.6%
• All patients demonstrated hematologic recovery by Day 26 without prolonged cytopenias.

Figure 1. CR rates in the ITT population and by subgroups* 

AML, acute myeloid leukemia; CR, complete remission; HMA, hypomethylating agent; ITT, intent-to-treat.
*Adapted from Altman, et al.¹

• Measurable residual disease negativity was achieved by 18.5% of patients in the ITT population and 50% of responders
• All patients experienced at least one treatment-emergent AE (Figure 2)
  • In total, 55% of patients died; 15% due to treatment-emergent AEs, including sepsis (n = 4) and pulmonary edema (n = 2)

Figure 2. Grade ≥3 TEAEs experienced with aspacytarabine in the ELPIS study* 

TEAE, treatment-emergent adverse event.
*Adapted from Altman, et al.¹