Wolfgang Däuble
Scientist at CeMM working with pharmacoscopy Photo courtesy of CeMM/
An ex vivo drug screening method can reveal optimal therapies for patients with hematologic malignancies, according to research published in The Lancet Haematology.
Researchers used a method called pharmacoscopy to measure single-cell responses to possible treatments in samples from patients with leukemias and lymphomas.
The team then used these results to guide treatment decisions and found that pharmacoscopy-guided treatment greatly improved response rates and progression-free survival (PFS).
“Having a robust, fast, and reliable predictive test at our disposal during the patient treatment process, especially at the time of relapse where a new intervention must be selected quickly, will change how medical doctors prioritize drugs to use for late-stage patients,” said study author Philipp Staber, MD, of Medical University of Vienna in Austria.
With pharmacoscopy, hundreds of drug options can be pre-tested ex vivo in small liquid biopsy samples collected from individual patients. The effects of each drug on the individual cells are quantified using high-throughput and high-content automated confocal microscopy.
In combination with specially developed analysis methods, machine learning, and other algorithms, pharmacoscopy allows quantification of never-before visualized phenotypes. The method was first described last April in Nature Chemical Biology.
Now, Dr Staber and his colleagues have reported, in The Lancet Haematology, an interim analysis of the first clinical trial testing pharmacoscopy-guided treatment.
There were 17 evaluable patients, all of whom had aggressive hematologic malignancies. This included diffuse large B-cell lymphoma (n=6), acute myeloid leukemia (n=3), B-cell acute lymphoblastic leukemia (n=2), precursor B-cell lymphoblastic lymphoma (n=1), peripheral T-cell lymphoma (n=1), primary mediastinal B-cell lymphoma (n=1), T-cell lymphoblastic lymphoma (n=1), follicular lymphoma (n=1), and T-cell prolymphocytic leukemia (n=1).
The researchers compared outcomes with pharmacoscopy-guided treatment to outcomes with the most recent regimen on which the patient had progressed.
The overall response rate was 88% with pharmacoscopy-guided treatment and 24% with the patients’ most recent previous treatment regimen (odds ratio=24.38; 95%, CI 3.99–125.4; P=0.0013).
None of the patients had progressive disease as their best overall response when they received pharmacoscopy-guided treatment. However, 7 patients had progressive disease in response to their most recent prior regimen.
At the time of analysis, 8 patients (47%) still had ongoing responses after pharmacoscopy-guided treatment.
In addition, pharmacoscopy-guided treatment significantly improved PFS. The median PFS was 22.6 weeks with pharmacoscopy-guided treatment and 5.7 weeks with the most recent prior regimen (hazard ratio=3.14; 95%, CI 1.37–7.22; P=0.0075).
“Evidence that the pharmacoscopy approach is helpful for clinical evaluation of therapy is wonderful,” said study author Giulio Superti-Furga, PhD, of CeMM Research Center for Molecular Medicine in Vienna, Austria.
“Single-cell functional analysis of primary material gives unprecedented resolution and precision that we are sure to further develop in the future to address yet more diseases.”
