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

Mar 17, 2020

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. 1An interview with Jeffrey E. Lancetdiscussing 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.Ryanand 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. 2These data were presented at the Transplantation & Cellular Therapy Meeting February, 19–23, 2020, Florida, US.

Methods 2

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

Results 2

  • 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% vs33%, 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 vs7+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 vs7+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% vs43%, 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 vs29 days and 37 vs28 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

  1. Lancet JE. et al.CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol. 2018 Sep 10; 36(26): 2684–2692. DOI:  10.1200/JCO.2017.77.6112
  2. Ryan DH .et al.Outcomes in Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes (AML-MRC) Who Achieved Remission with CPX-351 Versus 7+3: Phase 3 Exploratory Analysis. Biol Blood Marrow Transplant. 2020 March; 26(3): S9–S10. DOI: https://doi.org/10.1016/j.bbmt.2019.12.073