Subgroup analysis of outcomes in patients with AML-MRC who achieved remission with CPX-351 versus 7+3

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is associated with poor prognosis after induction therapy. CPX-351, a liposomal combination of daunorubicin (D) plus cytarabine (C), demonstrated a significantly improved median overall survival (OS) compared to a standard 7+3 regimen in older patients (60–75 years of age) with newly diagnosed high-risk or secondary AML.¹ An interview with Jeffrey E. Lancet discussing results of the trial is available here. You can also read about the impact of gene mutations on the efficacy of combination here.

Daniel H.Ryan and colleagues conducted an exploratory subgroup analysis of a phase III study (NCT01696084) comparing outcomes in patients who achieved complete remission (CR) or CR with an incomplete neutrophil/platelet recovery (CRi) across treatment groups.² These data were presented at the Transplantation & Cellular Therapy Meeting February, 19–23, 2020, Florida, US.

Methods²

• Patients were randomized to one or two induction cycles with
  • CPX-351 – 100 units/m² of C, 100 mg/m² + D, 44 mg/m² infusions on Days 1, 3, and 5 (2^nd induction: Days 1 and 3)
  • 7+3 – C 100 mg/m² daily continuously for seven days (2^nd induction: 5 days) + D 60 mg/m² on Days 1–3 (2^nd induction: Days 1–2)
• Patients in CR or CRi could receive two consolidation cycles with CPX-351 (65 units/m² of C, 65 mg/m² + D 29 mg/m² on Days 1 and 3) or 5 + 2 (as in 2^nd induction). Hematopoietic cell transplantation (HCT) was allowed at the physician's discretion

Results²

• In total, 246/309 of patients (80%) were diagnosed with AML-MRC, with 123 per treatment group
• There were more patients in CR + CRi in the CPX-351 group compared to the 7 + 3 group (48% vs 33%, respectively; odds ratio, 1.83; 95% CI, 1.09–3.09)
• Patients with AML-MRC, who achieved CR + CRi had longer median OS with CPX-351 vs 7+3 (19.5 vs 11.58; HR, 0.58; 95% CI, 0.34–0.96)
• OS from date of HCT was also higher in patients who received CPX-351 vs 7+3 (NR vs 14.09; HR, 0.61; 95% CI, 0.27–1.40)
• The HCT rate in AML-MRC patients with CR + CRi was higher with CPX-351 than with 7+3 (54% vs 43%, respectively; relative risk, 1.18; 95% CI, 0.79–1.76)
• The safety profile was similar between treatment groups, except there was a longer recovery of neutrophils and platelets with CPX-351 (35 vs 29 days and 37 vs 28 days, respectively) compared to the 7+3 regimen (Table 1)
  • No deaths were reported within 60 days post treatment

Table 1. Treatment-emergent adverse events

TEAE, treatment-emergent adverse event
TEAE	CPX-351 (n = 59)	7+3 (n = 40)
TEAEs in ≥ 50% of patients in either group, % Febrile neutropenia Constipation Nausea Peripheral edema Fatigue Diarrhea	78 58 53 49 47 37	80 55 53 65 50 78
Serious TEAEs in ≥ 10% of patients in either group, % Febrile neutropenia Decreased ejection fraction	10 8	13 10

Conclusions

The authors demonstrated improved median OS with CPX-351 compared to 7+3 chemotherapy in patients with AML-MRC who achieved CR + CRi. The safety profile in this subgroup was consistent with the overall study population.^1,2