CLINICAL APPLICATION OF AN EX‐VIVO PLATFORM TO GUIDE THE CHOICE OF DRUG COMBINATIONS IN RELAPSED/REFRACTORY LYMPHOMA; A PROSPECTIVE STUDY

Introduction: While combination therapy is the standard of care for relapsed/ refractory non-Hodgkin lymphoma (RR-NHL), choice combinations an individual patient empirical, and response rates remain poor. Here we explore use a hybrid experimental/analytic method termed Quadratic Phenotypic Optimization Platform (QPOP), prediction optimal drug from limited clinical material. This high-throughput platform identifies drug-combinations on ex-vivo biopsies using orthogonal array composite design to maximise search space. These features are potentially useful assess personalized efficacious among set drugs with single agent pre-clinical or activity in lymphoma. Methods: We performed prospective cohort study QPOP analysis RR-NHL. Participants included RR-NHL patients across two tertiary oncology centres Singapore, disease amenable biopsy blood/ marrow aspiration, recruited between 1st November 2017 7th August 2020- median follow up 20 months. scores were derived samples (approximately 1,000,000 cells/ patient) matrix known efficacy against NHL. Results shared treating physician, off-label QPOP-guided was offered absence options. The primary outcomes feasibility turnaround time analysis. secondary identification recurrent 2 3 drug-combinations, concordance results responses. Results: In this interim period, 36 comprising 19 B-NHL, 15 T/NK-NHL lymphomas (CL), age 57.5 years prior lines treatment. Successful (Z’ score >0.5) feasible 31/36 cases average turn-around 5.7 (±2.1) days. predicted frequent sensitivities Copanlisib-based B-NHL (n = 7/12), Romidepsin-based (4/11). Importantly, specific not entirely dependent dose Clinical responses after standard-of-care 15) QPOP-derived regimens 5) evaluable independent treatments 17/31 patients. had positive predictive value 100% negative 80% 20, p 0.008), AUC 0.838 (95%CI 0.626-1.051; 0.011). Complete achieved novel combinations, including Palbociclib-Everolimus Romidepsin-Bortezomib T/NK-NHL. Conclusions: Prediction sensitivity clinically applicable time-frame through also able identify effective therapy. research funded by: Funding all aspects project provided by Singapore Ministry Health's National Medical Research Council 'Singapore lYMPHoma translatiONal studY (SYMPHONY)' Open Fund Large Collaborative Grant (MOH-000205-03). Keywords: Combination Therapies, Aggressive B-cell lymphoma, T-cell Conflicts interests pertinent abstract S. De Mel Other remuneration: SDM inventor patent titled ‘Method For Predicting A Suitable Therapy’ (Patent Cooperation Treaty (PCT) Application No.: PCT/SG2020/050595). M. B. A. Rashid MBMAR W.-J. Chng Honoraria: Amgen, J&J, Celgene, BMS, Abbvie, Novartis, Takeda funding: Hummingbird WJC PCT/SG2020/050595) E. K. Chow Employment leadership position: KYAN Therapeutics Stock ownership: EKC D. Jeyasekharan Consultant advisory role: Turbine Ltd, AstraZeneca, Janssen MSD AstraZeneca. Educational grants: Perkin Elmer ADJ