1. Data from Functional Precision Medicine Provides Clinical Benefit in Advanced Aggressive Hematologic Cancers and Identifies Exceptional Responders
- Author
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Philipp B. Staber, Berend Snijder, Giulio Superti-Furga, Ingrid Simonitsch-Klupp, Niklas Zojer, Christoph C. Zielinski, Dominik Wolf, Cora Waldstein, Stefan Vogt, Katrina Vanura, Emiel van der Kouwe, Peter Valent, Renate Thalhammer, Ismet Srndic, Wolfgang R. Sperr, Cathrin Skrabs, Christian Sillaber, Edgar Selzer, Ilse Schwarzinger, Ann-Sofie Schmolke, Ana-Iris Schiefer, Julius Salamon, Reinhard Ruckser, Robin Ristl, Markus Raderer, Gerald W. Prager, Edit Porpaczy, Alexander Pichler, Michael Panny, Leopold Öhler, Katharina Ocko, Thomas Noesslinger, Peter Neumeister, Leonhard Müllauer, Katsuhiro Miura, Olaf Merkel, Elisabeth Menschel, Marius E. Mayerhoefer, Simone Lubowitzki, Trang Le, Stefan Kubicek, Gerhard Krajnik, Nikolaus Krall, Barbara Kiesewetter, Lukas Kenner, Lukas Kazianka, Ulrich Jaeger, Georg Hopfinger, Mir Alireza Hoda, Daniel Heintel, Tim Heinemann, Alexander W. Hauswirth, Bernd Lorenz Hartmann, Marcus Hacker, Wolfgang Gstöttner, Hildegard T. Greinix, Klaus Geissler, Alexander Gaiger, Maurizio Forte, Verena Felsleitner-Hauer, Ruth Exner, Harald Esterbauer, Martin Erl, Ruth Eichner, Sandra Eder, Michael Bergmann, Günther Bayer, Gregory I. Vladimer, Tea Pemovska, and Christoph Kornauth
- Abstract
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.Significance: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.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275
- Published
- 2023
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