Researchers at Dana-Farber Cancer Institute have developed a blood test that may alter the diagnosis and monitoring of multiple myeloma and its precursor conditions. The new method, known as SWIFT-seq, uses single-cell sequencing to profile circulating tumor cells (CTCs) in the blood, offering a noninvasive alternative to traditional bone marrow biopsies. A report on the technique was published by Lightbody et al in Nature Cancer.
“A lot of work has gone into the identification of genomic and transcriptomic features that predict worse outcome in multiple myeloma, but we are still lacking the tests to measure them in our patients,” explained senior author Irene M. Ghobrial, MD. “As a clinician, this is the type of next-generation test that I would want to order for my patients.”
Multiple myeloma can be preceded by conditions such as monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Traditionally, bone marrow biopsies have been used to assess risk and monitor genetic changes in patients with these conditions. However, these biopsies can be painful, and the accompanying technique, fluorescence in situ hybridization (FISH), often fails to provide clear results, leading to less effective risk assessment.
“It would be amazing if we had a blood-based test that can outperform FISH and that works in the majority of patients—we think SWIFT-seq may just be that test,” said Romanos Sklavenitis-Pistofidis, MD, PhD, co–first author.
SWIFT-seq: How It Works
SWIFT-seq offers an innovative alternative by allowing doctors to perform risk assessments and genetic monitoring using a simple blood test. Beyond counting CTCs, SWIFT-seq provides a detailed genetic profile, identifying key genetic changes crucial for understanding the disease. This method may surpass the accuracy of bone marrow tests such as FISH. Additionally, SWIFT-seq evaluates tumor growth rates and identifies important gene patterns that may predict patient outcomes—all from a single blood sample.
“SWIFT-seq is a powerful option, as it can measure the number of CTCs, characterize the genomic alterations of the tumor, estimate the tumor’s proliferative capacity, and measure prognostically useful gene signatures in a single test and from a blood sample,” said Dr. Ghobrial.
The study involved 101 patients and healthy donors, demonstrating that SWIFT-seq successfully captured CTCs in 90% of patients with MGUS, SMM, and multiple myeloma. Of note, it identified CTCs in 95% of patients with SMM and 94% of patients with newly diagnosed multiple myeloma—the groups most likely to benefit from improved risk stratification and genomic surveillance. SWIFT-seq can enumerate CTCs based on the tumor’s molecular barcode, rather than relying on cell surface markers. SWIFT-seq not only measures multiple clinically relevant features directly from a blood sample but also provides novel insights into the biology of tumor cell circulation.
“We identified a gene signature that we believe captures the tumor’s circulatory capacity and may partly explain some of the unexplained mysteries of myeloma biology,” said Elizabeth D. Lightbody, PhD, co–first author. “This can have a tremendous impact in how we think about curtailing tumor spread in patients with myeloma and could lead to the development of new drugs for patients.”
Disclosure: For full disclosures of the study authors, visit nature.com.
