PURPOSE: Functional precision medicine approaches, including ex vivo drug sensitivity, may improve individualized treatment selection. This is useful for T-cell lymphoma (TCL), which has limited treatment options and is more prevalent in Asian countries. In a previously published clinical feasibility study, quadratic phenotypic optimization platform (QPOP/Optim.AITM) was used to guide treatment in relapsed/refractory non-Hodgkin lymphoma. In this real-world clinical study, Optim.AITM was evaluated in a licensed clinical laboratory to identify effective individualized therapeutic options for Asian TCL patients, highlighting cases that have benefited from this approach. METHODS: Optim.AITM uses a hybrid experimental-analytical approach that predictively ranks all clinically actionable treatments within a 12-drug panel, using less than 1 million cells. A report is subsequently provided to the clinicians to aid their treatment decision. The response of Optim.AITM-guided treatment is then measured. RESULTS: Approximately 40% of the 23 samples received consist of angioimmunoblastic TCL (AITL). Optim.AITM reports were successfully generated for 18 samples, with a median turnaround time of 5 ± 2 working days. Two AITL and subcutaneous panniculitis-like TCL patients had complete response (18 months duration), based on Optim.AITM's suggested Romidepsin-based combinations. Another AITL patient experienced partial response (26 months duration) with a 3-drug combination (Venetoclax and chemotherapy). To date, 2/3 patients are still responding to the treatments. CONCLUSION: With a clinically actionable turnaround time, Optim.AITM offers alternative therapeutic options for rare, heterogenous malignancies like TCL. Additionally, frequently occurring top ranked treatments identified could uncover new therapies, which can be more broadly explored in Western populations.
