{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T16:33:23Z","timestamp":1793464403735,"version":"4.5.0"},"reference-count":53,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"667","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2022,10,19]]},"abstract":"<jats:p>\n                    Although combination therapy is the standard of care for relapsed\/refractory non-Hodgkin\u2019s 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                    <jats:italic>n<\/jats:italic>\n                    \u00a0=\u00a017) 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\u2013guided combination therapy in RR-NHL.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.abn7824","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T13:58:17Z","timestamp":1666187897000},"source":"Crossref","is-referenced-by-count":42,"title":["An ex vivo platform to guide drug combination treatment in relapsed\/refractory lymphoma"],"prefix":"10.1126","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9049-5622","authenticated-orcid":true,"given":"Jasmine","family":"Goh","sequence":"first","affiliation":[{"name":"Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"De Mel","sequence":"additional","affiliation":[{"name":"NUS Center for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University 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