The Beat AML study enrolled its first patient on November 16th 2016. Using a data cut-off of August 31st 2018 we have enrolled 285 newly diagnosed AML patients from twelve clinical sites. As of this morning we have enrolled 352 newly diagnosed AML patients. I’m going to share with you today the results, or the initial results, of our study.
Let’s start with why – why a precision medicine approach in AML? Acute myeloid leukaemia is the most commonly diagnosed adult leukaemia with 20,000 patients a year and an overall survival of 25%. It is also the most lethal adult leukaemia. We know now that AML is a heterogeneous disease, it’s driven by the serial acquisition of mutations that lead to inter-patient heterogeneity, both in biology and clinical response. This coupled with the increasing evidence of efficacy for targeted therapies in AML, we hypothesised – could we improve patient outcome by matching patients to the appropriate therapy?
The Beat AML trial is an umbrella study that requires genomic screening at the point of entry, the primary endpoint is the feasibility of making a treatment decision within seven days using this information and the individual efficacy of the sub-studies. Our eligibility criteria is broad and simple – you must be 60 years and older newly diagnosed AML.
Given the heterogeneity of the disease we utilised the algorithm that’s shown here in making our treatment assignments. The details of this algorithm are presented at this meeting by Dr Mims. Treatment assignments using this algorithm are based on the dominant clone defined by the variant allele frequency; all treatment assignments are done centrally and ultimately the treatment assignments are made based on what’s best for the patient, even if that means an assignment that is outside of the Beat AML study. The baseline demographics are shown on this slide. You can see that it’s primarily an older patient population with a high proportion of patients that are over 75 years in age.
The answer to the question of can we assign treatment using genomic information within seven days is yes. We’ve achieved our primary endpoint of assigning therapy within the seven days in over 95% of the patients. Looking at our enrolment and treatment assignments we’ve enrolled 356 patients based on the suspicion of AML. 66 patients were considered screen fail due to predominantly an alternative diagnosis in myeloid malignancies such as high risk MDS and CMML. Five patients were pending assignment at the time of the data cut-off. We assigned treatment for 285 patients and treatment assignment is shown here. More than 50% of the patients have gone on to therapy.
So what happened to the patients that did not go on to treatment? A small proportion, 2.5%, died within the initial seven day wait period. Another subset of patients went on to standard of care or alternative clinical trial after the treatment decision was made. You remember what I said – the treatment decisions are made for what’s best for the patient, even if that means a study outside of Beat AML. 8% went on to palliative care which is a special finding from this study that shows that some patients have the time to understand and comprehend their disease and therapeutic options and then choose not to pursue any therapy.
The study is large, we have eleven sub-studies from seven pharmaceutical partners and we’re active at 13 clinical sites as of this morning. We cover the prominent sub-types of AML. We continue to expand this collaborative effort and are looking to move into novel-novel combinations in the future.
So where are individual studies today? The majority of the patients are receiving therapeutic benefit but I’m only going to speak to the studies that are shown or being presented here at this meeting. For our marker negative group and hypermethylation group the phase Ib dose escalation combination of Boehringer Ingelheim CD33 antibody with azacitidine has been completed and the phase II study has been initiated. Details of this are going to be presented by Dr Blum tomorrow evening. For the IDH mutated patients the phase II study with enasidenib has been expanded. The initial overall response rate is 44.4% as monotherapy treatment for newly diagnosed patients. This work is being presented this morning by Dr Stein. For our core binding factor group this study has been discontinued.
So what have we demonstrated? That a precision medicine approach to assigning therapy within seven days using genomic information is feasible. Early death and disease progression is relatively uncommon except in the MLL rearranged AML patients. The majority of patients will go on to therapy and this continues to increase as we have more studies. We are seeing promising efficacy in newly diagnosed patients with this trial design. Thank you.