A randomised comparison of CPX-351 and FLAG-Ida in adverse karyotype AML and high-risk MDS: the UK NCRI AML19 trial

Liposomal daunorubicin and cytarabine (CPX-351) improves overall survival (OS) compared to 7+3 chemotherapy in older patients with secondary acute myeloid leukaemia (AML); to date there have been no randomized studies in younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) compared CPX-351 with FLAG-Ida in younger adults with newly-diagnosed adverse cytogenetic AML or high-risk myelodysplastic syndromes (MDS). 189 patients were randomized (median age 56y). By clinical criteria 49% had de novo AML, 20% secondary AML and 30% high risk MDS. MDS-related cytogenetics were present in 73% of patients, with complex karyotype in 49%. TP53 was the most commonly mutated gene, in 43%. Myelodysplasia-related gene mutations were present in 75 patients (44%). The overall response rate (CR + CRi) after course two was 64% and 76% for CPX-351 and FLAG-Ida (OR:0.54, 95%CI 0.28-1.04, p=0.06). There was no difference in OS (13.3 months vs 11.4 months, HR:0.78, 95%CI 0.55-1.12, p=0.17) or event-free survival (HR:0.90, 95%CI 0.64-1.27, p=0.55) in multivariable analyses. However, relapse-free survival was significantly longer with CPX-351 (median 22.1 vs 8.35 months, HR:0.58, 95% CI 0.36-0.95, p=0.03). There was no difference between the treatment arms in patients with clinically defined secondary AML (HR:1.1, 95%CI 0.52-2.30) or those with MDS-related cytogenetic abnormalities (HR:0.94, 95%CI 0.63-1.40), however an exploratory sub-group of patients with MDS-related gene mutations had significantly longer OS with CPX-351 (median 38.4 vs 16.3 months, HR:0.42, 95%CI 0.21-0.84, heterogeneity p=0.05). In conclusion, OS in younger patients with adverse risk AML/MDS was not significantly different between CPX-351 and FLAG-Ida

Evaluating the impact of an enhanced triage process on the performance and diagnostic yield of oesophageal physiology studies post COVID-19

OBJECTIVES: The COVID-19 pandemic significantly impacted on the provision of oesophageal physiology investigations. During the recovery phase, triaging tools were empirically recommended by national bodies for prioritisation of referrals amidst rising waiting lists and reduced capacity. We evaluated the performance of an enhanced triage process (ETP) consisting of telephone triage combined with the hierarchical ‘traffic light system’ recommended in the UK for prioritising oesophageal physiology referrals. DESIGN: In a cross-sectional study of patients referred for oesophageal physiology studies at a tertiary centre, data were compared between patients who underwent oesophageal physiology studies 6 months prior to the COVID-19 pandemic and those who were investigated within 6 months after service resumption with implementation of the ETP. OUTCOME MEASURES: Adjusted time from referral to investigation; non-attendance rates; the detection of Chicago Classification (CC) oesophageal motility disorders on oesophageal manometry and severity of acid reflux on 24 hours pH/impedance monitoring. RESULTS: Following service resumption, the ETP reduced non-attendance rates from 9.1% to 2.8% (p=0.021). Use of the ‘traffic light system’ identified a higher proportion of patients with CC oesophageal motility disorders in the ‘amber’ and ‘red’ triage categories, compared with the ‘green’ category (p=0.011). ETP also reduced the time to test for those who were subsequently found to have a major CC oesophageal motility diagnosis compared with those with minor CC disorders and normal motility (p=0.004). The ETP did not affect the yield or timing of acid reflux studies. CONCLUSION: ETPs can effectively prioritise patients with oesophageal motility disorders and may therefore have a role beyond the current pandemic