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- Title
An ex vivo platform to guide drug combination treatment in relapsed/refractory lymphoma.
- Authors
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; Ng, Siok-Bian
- 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.
- Subjects
SINGAPORE; NON-Hodgkin's lymphoma; COMBINATION drug therapy; B cells; DRUG efficacy; T cells; ALEMTUZUMAB
- Publication
Science Translational Medicine, 2022, Vol 14, Issue 667, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.abn7824