Treatment options for acute myeloid leukemia (AML) have improved rapidly, with nearly a dozen new approvals within 5 years. Yet despite these advances, the majority of AML patients are not cured, and long-term survival remains unacceptably low. Poor long-term outcomes are associated with the presence of residual leukemia, persisting below the limits of standard clinical detection, which expands over time and leads to AML relapse. AML in the relapsed setting has few effective treatment approaches, with an average life expectancy at relapse of < 6 months. With advances in flow cytometric and molecular quantification of measurable residual disease (MRD), we hypothesize that using these techn...

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Treatment options for acute myeloid leukemia (AML) have improved rapidly, with nearly a dozen new approvals within 5 years. Yet despite these advances, the majority of AML patients are not cured, and long-term survival remains unacceptably low. Poor long-term outcomes are associated with the presence of residual leukemia, persisting below the limits of standard clinical detection, which expands over time and leads to AML relapse. AML in the relapsed setting has few effective treatment approaches, with an average life expectancy at relapse of < 6 months. With advances in flow cytometric and molecular quantification of measurable residual disease (MRD), we hypothesize that using these technologies to identify and treat patients pre-emptively, at the "MRD positive" stage, will be more effective than the current treatment strategy of waiting for overt leukemia progression, ultimately providing higher quality and long-lasting remissions with less treatment-related toxicity and an improved quality of life.

Through the INTERCEPT study, we have established a new clinical trial platform to validate the feasibility and efficacy of novel therapies and therapeutic combinations in this MRD setting. We have developed a Master Protocol that standardizes the monitoring of MRD in patients with AML in clinical remission, established highly sensitive and accurate MRD assays to enable timely detection of MRD, and confirmed the supply of novel therapies for MRD-directed interventions.

We hypothesize that leukemia-directed therapy, employed in molecularly-defined and rational precision-based combinations in the MRD setting, will lead to eradication of residual leukemia and ultimately improve patient outcome through an individualized, practice-changing, curative treatment approach. Through the application of innovative technology such as single cell sequencing and proteomic analysis, we will further detail the patterns of leukemia response and resistance to MRD-directed therapy.

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