RATIONAL DESIGN OF OPTIMISED THERAPEUTICS AGAINST RELAPSED / REFRACTORY NON-HODGKIN LYMPHOMA

Abstract

Quadratic Phenotypic Optimisation Platform (QPOP) provides a rational approach towards personalising drug combination treatments. We showed in cancer cell line models, that resolution for QPOP experimental combination design can be reduced without compromising drug combination optimisation. Next, clinical application of QPOP was tested in 75 relapsed/refractory non-Hodgkin lymphoma (RR-NHL) patients, with a median of 2 prior lines of treatment. Fresh biopsies underwent ex vivo testing using drugs with known efficacies against NHL, and QPOP analysis was feasible in 67/75 cases, with a median turnaround time of 6 days. Off-label QPOP-guided therapy offered at physician discretion resulted in complete responses and the rate of progressive disease was also reduced in patients who have received ≥3 prior lines of therapy. Overall, this work demonstrates the feasibility of optimising drug combinations within a clinically actionable timeframe and forms the foundation for a prospective clinical trial to evaluate QPOP-guided combination therapy in RR-NHL.