Data from Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders
Authors: Kornauth Christoph , Pemovska Tea , Vladimer Gregory I. , Bayer Günther , Bergmann Michael , Eder Sandra , Eichner Ruth , Erl Martin , Esterbauer Harald , Exner Ruth , Felsleitner-Hauer Verena , Forte Maurizio , Gaiger Alexander , Geissler Klaus , Greinix Hildegard T. , Gstöttner Wolfgang , Hacker Marcus , Hartmann Bernd Lorenz , Hauswirth Alexander W. , Heinemann Tim , Heintel Daniel , Hoda Mir Alireza , Hopfinger Georg , Jaeger Ulrich , Kazianka Lukas , Kenner Lukas , Kiesewetter Barbara , Krall Nikolaus , Krajnik Gerhard , Kubicek Stefan , Le Trang , Lubowitzki Simone , Mayerhoefer Marius E. , Menschel Elisabeth , Merkel Olaf , Miura Katsuhiro , Müllauer Leonhard , Neumeister Peter , Noesslinger Thomas , Ocko Katharina , Öhler Leopold , Panny Michael , Pichler Alexander , Porpaczy Edit , Prager Gerald W. , Raderer Markus , Ristl Robin , Ruckser Reinhard , Salamon Julius , Schiefer Ana-Iris , Schmolke Ann-Sofie , Schwarzinger Ilse , Selzer Edgar , Sillaber Christian , Skrabs Cathrin , Sperr Wolfgang R. , Srndic Ismet , Thalhammer Renate , Valent Peter , van der Kouwe Emiel , Vanura Katrina , Vogt Stefan , Waldstein Cora , Wolf Dominik , Zielinski Christoph C. , Zojer Niklas , Simonitsch-Klupp Ingrid , Superti-Furga Giulio , Snijder Berend , Staber Philipp B. 
Published: April 2023

<div>Abstract<p>Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers.</p>Significance:<p>This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.</p><p><i><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-21-1498" target="_blank">See related commentary by Letai, p. 290</a>.</i></p><p><i><a href="https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-12-2-ITI" target="_blank">This article is highlighted in the In This Issue feature, p. 275</a></i></p></div>