Prospective Clinical Validation of a Combinatorial Functional Precision Medicine Platform in Relapsed/Refractory Non-Hodgkin's Lymphoma.

Abstract

Purpose: Despite initially responding to first-line treatment, many patients with non-Hodgkin's lymphoma (NHL) eventually relapse or are refractory. These patients are empirically subjected to salvage therapies that may not be efficacious. We had previously presented feasibility evidence of an ex vivo functional precision medicine (FPM) platform, quadratic phenotypic optimization platform (QPOP), being potentially useful in identifying alternative therapeutic options for patients with relapsed/refractory (R/R)-NHL. We now present an analysis of the completed prospective study, with clinical concordance and benefit of QPOP in predicting treatment responses of patients with R/R-NHL.

Materials and methods: One hundred seventeen patients with R/R B-cell NHL (B-NHL) or natural killer or T-cell NHL (NK/T-NHL) were recruited for QPOP testing. Isolated tumor cells were incubated for 48 hours with drug combinations determined by an orthogonal array composite design. QPOP reports with patient-specific optimal drug therapies were generated. Patients were given off-label treatments according to the clinician's decision. Patient characteristics and responses to treatments after QPOP testing were recorded.

Results: Within 126 QPOP cases, 105 (52 B-NHL and 53 NK/T-NHL) were evaluable. QPOP-suggested drug responses were concordant with actual patient outcome, with an overall test accuracy of 74.5%. An overall response rate of 59% was achieved in those prescribed off-label QPOP-guided combinations. In all, 59.3% of QPOP-guided patients had improved response durations compared with their previous treatment. Compared with those who received salvage therapy, QPOP-guided patients also had longer progression-free survival 2 years after treatment.

Conclusion: There is increasing evidence that genetic factors are not sole determinants of patient drug response and FPM approaches may improve cancer treatment guidance. This study further confirms that advancements in ex vivo combinatorial drug screening platforms like QPOP could complement existing genomic methods in identifying effective treatment options for patients with cancer, especially in R/R cases.