Feasibility of predicting AML response to induction chemotherapy

Abstract There is a critical unmet medical need for a rapid accurate test to identify AML patients who are likely to respond to chemotherapy Presently induction chemotherapy with the DNA damaging drugs cytarabine ARA C and idarubicin IDR known as is the standard of care for most of these patients However is a relatively ineffective therapy particularly in older patients and has serious therapy related toxicities Accelerated Medical Diagnostics is developing the InductDx test to identify those patients whose AML will respond to induction chemotherapy The test utilizes ex vivo andquot diagnostic microdosesandquot of the therapeutic dose of C labeled ARA C and C labeled IDR Extremely low levels of C label are quantified in cancer cells isolated from patient blood samples using accelerator mass spectrometry AMS AMS is the most sensitive technology available for quantifying radiolabeled compounds in biological samples We hypothesize that a threshold level of drug DNA damage is required for efficacy and the level of microdose induced drug DNA damage is predictive of the capacity of AML cells to attain that threshold during in vivo chemotherapy The extent of microdose induced drug DNA damage in cell cultures and AML patient samples will be compared with cellular sensitivities and retrospective patient response to therapy as proof of concept for clinical development of the InductDx test for AML We propose to develop a rapid clinically actionable ex vivo biomarker test to predict which AML patients will respond to cytarabine and idarubicin combination chemotherapy This platform technology will enable improved treatment outcomes for AML and other cancers