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Summary: Improving outcomes for older patients with acute myeloid leukaemia remains an unmet need. As part of the LI‐1 trial, we evaluated lenalidomide (LEN) in combination with low‐dose cytosine arabinoside (LDAC) in patients aged >60 years unfit for intensive therapy and compared this to LDAC alone. Two hundred and two patients, randomised 1:1, were evaluable. Overall response rate (CR + CRi) was higher for LDAC + LEN versus LDAC (26% and 13.7% respectively p = 0.031). However, there was no difference in overall survival between the arms (14% and 11.5% at 2 years for LDAC + LEN and LDAC respectively). The addition of LEN was associated with increased toxicity and supportive care requirements. [ABSTRACT FROM AUTHOR]

Summary: The survival of acute myeloid leukaemia (AML) patients aged over 60 has been suboptimal historically, whether they are treated using hypomethylating agents, low‐dose cytarabine (LDAC) or venetoclax‐based regimens. Progress is being made, however, for subgroups with favourable molecular or cytogenetic findings. Arginine metabolism plays a key role in AML pathophysiology. We report the only randomised study of LDAC with recombinant arginase BCT‐100 versus LDAC alone in older AML patients unsuitable for intensive therapy. Eighty‐three patients were randomised to the study. An overall response rate was seen in 19.5% (all complete remission [CR]) and 15% (7.5% each in CR and CR without evidence of adequate count recovery [CRi]) of patients in the LDAC+BCT‐100 and LDAC arms respectively (odds ratio 0.73, confidence interval 0.23–2.33; p = 0.592). No significant difference in overall or median survival between treatment arms was seen. The addition of BCT‐100 to LDAC was well tolerated. [ABSTRACT FROM AUTHOR]

Summary: Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front‐line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real‐world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available. [ABSTRACT FROM AUTHOR]

Summary: Older patients with acute myeloid leukaemia (AML) account for nearly half of those with the disease. Because they are perceived to be unfit for, unwilling to receive, or unlikely to benefit from conventional chemotherapy they represent an important unmet need. Tosedostat is a selective oral aminopeptidase inhibitor, which in phase I/II trials showed acceptable toxicity and encouraging efficacy. We report the only randomised study of low‐dose cytosine arabinoside (LDAC) combined with tosedostat (LDAC‐T) versus LDAC in untreated older patients not suitable for intensive treatment. A total of 243 patients were randomised 1:1 as part of the 'Pick‐a‐Winner' LI‐1 trial. There was a statistically non‐significant increase in the complete remission (CR) rate with the addition of tosedostat, LDAC‐T 19% versus LDAC 12% [odds ratio (OR) 0·61, 95% confidence interval (CI) 0·30–1·23; P = 0·17]. For overall response (CR+CR with incomplete recovery of counts), there was little evidence of a benefit to the addition of tosedostat (25% vs. 18%; OR 0·68, 95% CI 0·37–1·27; P = 0·22). However, overall survival (OS) showed no difference (2‐year OS 16% vs. 12%, hazard ratio 0·97, 95% CI 0·73–1·28; P = 0·8). Exploratory analyses failed to identify any subgroup benefitting from tosedostat. Despite promising pre‐clinical, early non‐randomised clinical data with acceptable toxicity and an improvement in response, we did not find evidence that the addition of tosedostat to LDAC produced a survival benefit in this group of patients with AML. International Standard Randomised Controlled Trial Number: ISRCTN40571019 [ABSTRACT FROM AUTHOR]

Many older patients with acute myeloid leukaemia ( AML) that receive standard intensive chemotherapy fail to achieve complete remission ( CR). Upfront identification of patients unlikely to benefit from standard induction chemotherapy would be important for exploration of novel therapies. This study evaluated if a flow cytometric assay measuring pre-treatment CD34+ CD38low blast frequency could predict therapeutic-resistance in 736 AML patients entered into the UK National Cancer Research Institute AML16 trial. High peripheral blood CD34+ CD38low blast frequency (>7% of leucocytes), present in 18% of assessable patients, conferred significantly reduced CR rates (38% vs. 76%, P < 0·0001) and poor survival, and was independently prognostic for all endpoints of treatment resistance by multivariate analysis. [ABSTRACT FROM AUTHOR]

Many older patients with acute myeloid leukaemia (AML) that receive standard intensive chemotherapy fail to achieve complete remission (CR). Upfront identification of patients unlikely to benefit from standard induction chemotherapy would be important for exploration of novel therapies. This study evaluated if a flow cytometric assay measuring pre-treatment CD34(+) CD38(low) blast frequency could predict therapeutic-resistance in 736 AML patients entered into the UK National Cancer Research Institute AML16 trial. High peripheral blood CD34(+) CD38(low) blast frequency (>7% of leucocytes), present in 18% of assessable patients, conferred significantly reduced CR rates (38% vs. 76%, P < 0.0001) and poor survival, and was independently prognostic for all endpoints of treatment resistance by multivariate analysis., (© 2015 John Wiley & Sons Ltd.)