Ann: Race Strategic Update August 2023, page-348

The problem appears to be more or less universal given the current thinking in the AML haematology community around EMD AML. There is a recognition that EMD is an important issue (hence why the strong clinician interest in being part of trials), but since there are no specific treatments for EMD AML it is not seen as important to know if an individual r/r AML patient has EMD or not. Of course unless EMD is diagnosed first you can't develop treatments is one of those chicken-and-the-egg type problems all too common in medicine.

A similar thing happened with clinician thinking around minimal residual disease (MRD) in AML. It has been known for almost two decades in other leukemias that MRD status is very important for disease outcome post stem cell transplant, but due to technical issues diagnosing MRD in AML it was not considered by most clinicians for AML patients. This all changed about 3 years ago when various breakthroughs in flow cytometry and DNA sequencing allowed MRD status to be routinely determined in AML patients and this has revolutionised the treatment of AML. Getting a patient to MRD(-) before transplant is now the goal for AML patients able to tolerate a stem cell transplant.

The solution to the EMD trial problem is to remove the requirement for prescreening in the EMD AML trial and allow any patient the doctor suspects has EMD to enrol for treatment with bisantrene. Once on the trial the patient could then be checked for EMD without delaying treatment. I did ask Michelle on Friday why this was not the plan for the proposed new RAC-009 AML trial, but I didn't understand her answer. Maybe someone who was there could comment.