1. An ex vivo platform to guide drug combination treatment in relapsed/refractory lymphoma.
- Author
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Goh, Jasmine, De Mel, Sanjay, Hoppe, Michal M., Mohd Abdul Rashid, Masturah Bte, Zhang, Xi Yun, Jaynes, Patrick, Ka Yan Ng, Esther, Rahmat, Nur'Atiqa Diana Binti, Jayalakshmi, Liu, Clementine Xin, Poon, Limei, Chan, Esther, Lee, Joanne, Chee, Yen Lin, Koh, Liang Piu, Tan, Lip Kun, Soh, Teck Guan, Yuen, Yi Ching, Loi, Hoi-Yin, and Ng, Siok-Bian
- Subjects
NON-Hodgkin's lymphoma ,COMBINATION drug therapy ,B cells ,DRUG efficacy ,T cells ,ALEMTUZUMAB - Abstract
Although combination therapy is the standard of care for relapsed/refractory non-Hodgkin's lymphoma (RR-NHL), combination treatment chosen for an individual patient is empirical, and response rates remain poor in individuals with chemotherapy-resistant disease. Here, we evaluate an experimental-analytic method, quadratic phenotypic optimization platform (QPOP), for prediction of patient-specific drug combination efficacy from a limited quantity of biopsied tumor samples. In this prospective study, we enrolled 71 patients with RR-NHL (39 B cell NHL and 32 NK/T cell NHL) with a median of two prior lines of treatment, at two academic hospitals in Singapore from November 2017 to August 2021. Fresh biopsies underwent ex vivo testing using a panel of 12 drugs with known efficacy against NHL to identify effective single and combination treatments. Individualized QPOP reports were generated for 67 of 75 patient samples, with a median turnaround time of 6 days from sample collection to report generation. Doublet drug combinations containing copanlisib or romidepsin were most effective against B cell NHL and NK/T cell NHL samples, respectively. Off-label QPOP-guided therapy offered at physician discretion in the absence of standard options (n = 17) resulted in five complete responses. Among patients with more than two prior lines of therapy, the rates of progressive disease were lower with QPOP-guided treatments than with conventional chemotherapy. Overall, this study shows that the identification of patient-specific drug combinations through ex vivo analysis was achievable for RR-NHL in a clinically applicable time frame. These data provide the basis for a prospective clinical trial evaluating ex vivo–guided combination therapy in RR-NHL. Predicting possibilities with PDXs: Patients with non-Hodgkin's lymphomas (NHLs) often relapse after frontline treatment, and interpatient heterogeneity make personalized combination treatment difficult. Goh et al. have developed a hybrid experimental-analytic method that they call quadratic phenotypic optimization platform, or QPOP, to identify personalized drug combination therapies using ex vivo patient samples to improve patient outcomes. In a prospective cohort, physicians were able to alter treatment according to drug combinations identified using QPOP after 6 days to achieve complete responses in 5 of 17 patients with NHL. This is a promising step for providing new hope for patients who have relapsed NHL and provides a foundation for further clinical trials. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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