A research collaboration between several Dana-Farber investigators — Prof. Irene Ghobrial, PhD, Prof. Kenneth Anderson, MD, and Romanos Sklavenitis-Pistofidis, MD, PhD — and Gad Getz, of Massachusetts General Hospital and the Broad Institute, developed a new diagnostic liquid biopsy platform to profile patients with hematological cancers, like multiple myeloma. The platform may guide therapeutic strategies by focusing on the best potential treatments, sparing patients from undue toxicity and wasted time with ineffective treatments.
Multiple myeloma poses significant challenges for patients due to its propensity for relapses and variable survival rates. Traditional diagnostic tools for the disease, notably bone marrow biopsy and FISH (fluorescence in situ hybridization), fall short of meeting the needs of both clinicians and patients. FISH, a method for pinpointing disease-contributing genetic abnormalities, grapples with a 30-50% failure rate, frequently missing or overlooking crucial genomic aberrations pivotal for guiding therapy. Bone marrow biopsy, marked by its discomfort and inconvenience, necessitates repeated procedures after relapse, subjecting patients to a cycle of 10-15 biopsies in a lifetime.
While the FDA has approved over 20 drugs for multiple myeloma, the lack of a precise blood-based method to pinpoint ideal treatment candidates remains a critical gap. This is a challenge even for some of the most promising immunotherapies targeting B cell maturation antigen (BCMA) or G protein–coupled receptor class C group 5 member D (GPRC5D) that have emerged as important targets in multiple myeloma over the last few years.
This platform is designed to overcome the known limitations of FISH and bone marrow biopsy-based diagnostic methods.
The team’s new technology hinges on whole genome sequencing (WGS) of circulating tumor cells (CTCs) and single-cell sequencing of immune cells isolated from blood samples. This approach offers a heightened level of accuracy in diagnosing and predicting the prognosis of multiple myeloma compared to FISH.
WGS from CTCs in blood or bone marrow samples identifies cytogenetic abnormalities, like BCMA loss, translocations, and copy number variations, not detected by FISH. Single-cell immune cell and T-cell receptor (TCR) sequencing acts as an immune sensor. Changes in immune cell composition, gene expression, or clonality may underlie disease progression or response to therapy.
Patterns in immune cell signature inclusive of cells like CD8+ T cells, Tregs, and others, could provide information on immune dysregulation and response to therapy, helping to identify patients with improved survival to a specific therapy.
Team Members: Irene Ghobrial, MD, Kenneth Anderson, MD, Gad Getz, PhD, Romanos Sklavenitis-Pistofidis, MD, PhD
This platform has potential for clinical diagnostic benefit for patients with multiple myeloma and other hematological cancers such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) and could also be used to identify and prioritize novel targets for future therapeutic discoveries.
Potential uses may also include minimal residual disease therapeutic monitoring, and post-transplant monitoring.
This technology will now undergo further development tailored for clinical use within a new company.
This platform is being developed and commercialized within a new company, Predicta Biosciences, that originated from the labs of Dana-Farber.
Senior Vice President, Experimental Medicine
Director, Center for Early Detection and Interception of Blood Cancers
Co-Leader, Lymphoma/Myeloma Cancer Center Program
Lavine Family Chair for Preventative Cancer Therapies, Dana-Farber
Professor of Medicine, Harvard Medical School
Director, LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center, Dana-Farber
Kraft Family Professor of Medicine, Harvard Medical School
Director, Cancer Genome Computational Analysis at the Broad Institute of MIT and Harvard
Director of bioinformatics in the Krantz Family Center for Cancer Research and Department of Pathology at Massachusetts General Hospital.
Department of Medical Oncology, Dana-Farber
Instructor in Medicine, Harvard Medical School
