Clinical Evaluation of a Functional Combinatorial Precision Medicine Platform to Predict Patient-Specific Treatment Outcomes in Acute Myeloid Leukemia

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.2276-2276
• Main Authors: Chow, Edward, Meera Sahib, Noor Rashidha Binte, Rashid, Masturah, Lim, Jhin Jieh, Jen, Wei-Ying, Ooi, Melissa
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-186251

Introduction: Acute myeloid leukemia (AML) is an aggressive form a leukemia that remains difficult to treat, often with rapid and frequent disease relapse due to drug-resistant clonal selection. A range of combination therapies have been designed to overcome this hurdle, however, identifying the most appropriate combination therapy at each line of treatment remains a challenge. Functional precision medicine platforms that use ex vivo drug sensitivity data from primary patient samples have shown potential to guide treatments in a range of cancers. We have recently developed an ex vivo combinatorial drug sensitivity platform, quadratic phenotypic optimization platform (QPOP), that analyses a predesigned array of 155 test combinations performed on a primary patient sample to rank and compare all possible therapeutic combinations from a 12-drug set. In this study, we evaluated the use of QPOP to predict treatment outcomes in an AML cohort treated with a variety of combination therapies. Furthermore, we also explored QPOP's combination therapy ranking function to identify novel or under-utilized combinations that may benefit larger groups of AML patients when appropriately guided. Methods: Prospective clinical feasibility study of QPOP in AML was performed at National University Hospital (NUH) in Singapore. Peripheral blood or bone marrow aspirations were collected from AML patients, recruited between 26 th November 2019 and June 15 th 2023. Following CD34+ cell selection, the enriched malignant blast population was subjected to an array of 155 test combinations derived from an orthogonal array composite design. Phenotypic cell viability data from this test was subsequently used by QPOP to derive drug combination scores and rankings for all possible combinations. Median turnaround time for QPOP patient-specific reports was 8 (±2.1) days. Patients were treated with current standard of care options as guided by the clinician. The primary outcomes of this study were to determine the concordance between treatment outcomes as guided by clinicians and QPOP drug combination scores and rankings. Secondary outcomes of this study were to identify high-ranking, potentially effective combinations that may be nover or under-utilized for future studies. Results: 40 patients were recruited to the study with 49 samples analyzed by QPOP. Samples collected until 21 January 2022 were also used to refined ex vivo drug dosing levels for 12-drug, 3-level test combination arrays. Exc