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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 ., (©2021 The Authors; Published by the American Association for Cancer Research.)

Background: In addition to conventional chemotherapeutic regimens and autologous transplantation, novel agents are now part of the treatment armamentarium against multiple myeloma (MM). To evaluate the presumed benefit of novel agents, we performed an analysis of patients with MM at our institution before and after the availability of novel agents., Design and Methods: In all, 200 consecutive patients with newly diagnosed MM (male = 119; female = 81; median age: 61.5 years) treated at our institution between June 1993 and December 2008 were included in this retrospective analysis. Patient cohorts were defined according to date of diagnosis (before and after 01-Jan-2000, respectively), treatment received (chemotherapy only vs. therapy including novel agents), risk profile (International Staging System (ISS)-stage), and cytogenetic features. Primary focus of the analysis was overall survival (OS)., Results: Median OS for MM patients who received conventional chemotherapy was 45.2 months and for patients who received novel agents 74.6 months (P < 0.01). OS for those patients who relapsed after autotransplantation before 2000 was 35.2 months, but 72.7 months (P < 0.01) for those patients with a later relapse. Prolongation of survival for patients receiving novel agents was most evident for patients with ISS stage III (median OS 68.4 vs. 11.2 months for patients with chemotherapy only; P < 0.01). MM patients with an intermediate risk had a longer median OS when receiving novel agents (47.2 vs. 32.8 months)., Conclusion: Treatment with novel agents in MM resulted in a significant prolongation of OS. Benefit of therapy with novel agents was particularly evident for transplant-eligible patients and MM patients with unfavorable prognosis.