P500: A REAL WORLD MULTI CENTRE STUDY OF CPX-351 REVEALS NO DIFFERENCE IN OVERALL SURVIVAL WHEN COMPARED WITH FLAG-IDA AND 3 + 7 IN HIGH RISK AML.

Abstract

Background: CPX-351 is a liposomal formulation of daunorubicin and cytarabine in a fixed synergistic ratio of 5:1. It has been approved by both the FDA and EMA for use in high-risk AML including therapy related AML (t-AML) and AML with myelodysplastic related change (AML-MRC). However, this is little data of CPX-351 in a real-world setting. There is also no data comparing CPX-351 to FLAG-IDA which is used in our institution front line for high-risk AML Aims: The objective of our multi-centre study was to assess outcomes of CPX-351 and then compare these outcomes in patients who received FLAG-IDA and 3 + 7 for high risk AML(tAML and AML-MRC). Methods: Patients aged 18 and over who were treated with induction chemotherapy and who met the WHO criteria for t-AML and AML-MRC were included in the study. Retrospective data was collected from 10 centres throughout Canada for CPX-351. The Princess Margaret Cancer Centre database was used to collect data for patients who received induction with FLAG-IDA and 3 + 7. Targeted sequencing was performed on DNA samples using the TruSight Myeloid Sequencing Panel. Overall survival (OS) and progression free survival (PFS) rates were calculated using the Kaplan-Meier method. Results: 76 patients treated with CPX-351 were identified with baseline characteristics seen on Table 1. Targeted sequencing was performed on 72% of patients (55/76) and the average number of mutations was 2(0-7). RUNX1 was the most commonly mutated gene found in 22% (12/55), followed by ASXL1 mutated in 19% (10/55) and SRSF2 in 15%. Assessing treatment responses, 53% (38/76) of patients achieved a complete remission (CR) or a complete remission with incomplete recovery (CRi). The median CR duration was short at 7.3 months. Median follow up was 7.78 months (range 0.2 to 20 months). OS was 57% at 12 months and 38% at 18 months. PFS was 40% at 12 months and 23% at 18 months. There were no differences in OS when stratified by ELN risk (p=0.46), adverse risk cytogenetics (p=0.1485), or poor risk mutations such as RUNX1 (p=0.73), ASXL1 (p=0.47) or TP53(p=0.53).Patients who received an ASCT had significant improvement of OS of 82% at 18 months compared to those who did not receive a transplant of 15% at 18 months (Fig 2; p=0.0001). Patients who received 3 + 7 and FLAG-IDA for the same indications as CPX-351 (tAML and AML-MRC) were identified. Baseline characteristics are shown in Table 1. 69% of patients receiving FLAG-IDA and 67% of those receiving 3 + 7 had adverse ELN risk stratification. CR rates were highest with FLAG IDA with 75% achieving a CR or CRi. 68% of patients who received CPX-351 proceeded to ASCT compared with 59% with FLAG-IDA and 57% with 3 + 7. OS at 18 months was 42% for FLAG-IDA and 39% for 3 + 7. There was no statistical difference in OS when comparing CPX-351 to FLAG-IDA and 3 + 7 (p=0.855) (Figure 1). Similarly, there was no difference in PFS when comparing all 3 inductions (p=0.26). Patients who received a ASCT had significant improvement of OS of 59% at 18 months compared to those who did not receive a transplant of 24% at 18 months (p=<0.0001)irrespective of what induction was used. Image:Summary/Conclusion: High risk AML remains an unmet clinical need which is supported by our study which reveals no difference in OS or PFS when treated with either CPX-351, FLAG-IDA or 3 + 7. Unsurprisingly, ASCT improved OS across all patients irrespective of induction type. Further study with a prospective randomised control trial is required.