How Blood-Based Liquid Biopsies Could Transform Multiple Myeloma Monitoring

Blood-based tests known as "liquid biopsies" are becoming powerful tools for diagnosing, monitoring, and tracking multiple myeloma. These tests look at the number of cancer cells and genetic material fragments in the blood circulating through the body. Liquid biopsies may eventually reduce the need for repeated bone marrow biopsies, which can be challenging for people with myeloma. At the 2026 World Congress on Controversies in Multiple Myeloma (COMy), Dr. Joaquín Martínez López presented an overview of these tests and how they may change how multiple myeloma is monitored. 

How are liquid biopsies used for multiple myeloma?

Multiple myeloma is a cancer of plasma cells. These cells are normally found in the bone marrow. Bone marrow is the spongy tissue at the center of large bones that produces blood cells. To diagnose myeloma and follow how it changes over time, doctors usually rely on bone marrow biopsies. The results from these tests allow them to follow how well treatments are working to control myeloma. But this procedure can be uncomfortable, and it is difficult to repeat often.

A liquid biopsy is a test that measures the amount of cancer cells and DNA fragments in the blood and other body fluids. In myeloma, liquid biopsies have two main targets:  

• Circulating tumor cells (CTCs) are myeloma cells that have escaped from the bone marrow into the bloodstream

• Circulating tumor DNA (ctDNA) are the small fragments of genetic material released by cancer cells. 

According to Dr. Martínez López, liquid biopsies are minimally invasive and can be repeated as often as needed. These tests can capture more of the diversity of cancer cells throughout the body than a single bone marrow sample.

However, there are challenges, too. CTCs in the blood are roughly 100 to 2,000 times less abundant than cancer cells in the bone marrow. This makes them harder to find. Even so, levels of cell-free DNA in the blood are closely related to how much disease a patient has, and ctDNA tends to be higher in myeloma than in many other cancers. This makes peripheral blood a promising place to look. Peripheral blood is the blood circulating throughout the body.

Liquid biopsies are being studied as tools to find patients who need treatment earlier, support diagnosis and prognosis, monitor how well a therapy is working, guide treatment choices, and follow clonal evolution. Clonal evolution refers to the genetic changes that happen as myeloma cells adapt and become resistant to therapies or the immune system.

BloodFlow? A new ultra-sensitive blood test that can detect rare myeloma cells

One of the standout advances Dr. Martínez López described was a new test called BloodFlow. This liquid biopsy was developed in collaboration with the Spanish Myeloma Group. The test uses 50 ml of blood, which is more than standard blood tests. After the blood is collected, it is purified and tested using flow cytometry. Flow cytometry is a laboratory method that identifies immune markers on the cells surface.

BloodFlow reaches a sensitivity of 10⁻⁷. This means it can find one myeloma cell among 10 million normal cells. According to Dr. Martínez López, researchers identified around 15% of patients as being at a higher risk of their myeloma progressing using this test. 

Earlier research has shown other ways these tests can be used to determine risk. The Spanish GEM2012 clinical trial found that patients with no detectable CTCs tended to have a very good prognosis. 

Reading tumor DNA in the blood: insights from research groups around the world

Several teams are also making progress in detecting and analyzing ctDNA. In a study of 51 patients, a Dana-Farber research group purified circulating tumor cells and used shallow genetic sequencing. They were able to identify molecular abnormalities and changes after treatment. Another clinical trial that enrolled 57 patients looked at a different highly sensitive DNA test. They were able to successfully identify subgroups of patients with a poor prognosis or higher risk of disease progression. A Miami research group used whole-genome sequencing in a 25-patient proof-of-concept study. They found about 71% agreement with bone marrow results, meaning that in roughly 7 out of every 10 patients, the blood test and the bone marrow biopsy gave the same answer Importantly, the test also picked up signs of myeloma in some patients whose bone marrow had come back clean. 

A San Francisco research group's CAPP-Seq panel detected ctDNA in most patients receiving CAR T-cell therapy. The ctDNA levels at days 14 and 28 helped predict treatment success for patients. Dr. Martínez López's group also developed a very sensitive test that can help predict relapse. 

Tracking resistance mutations and clonal evolution

Dr. Martínez López's team is also focused on detecting specific mutations. They are focused on mutations that drive resistance to newer therapies, including changes in BCMA and GPRC5D, both targets of modern myeloma immunotherapies. In collaboration with a Barcelona group, they developed a single-cell sequencing panel for free DNA that can detect ctDNA in 80% of patients.  In this study, researchers used long-read sequencing. This is a newer method that reads long stretches of DNA at once, allowing scientists to see genetic changes that shorter methods can miss. The team made an unexpected observation: patients can carry long fragments of free DNA in their blood. This is surprising because free DNA in the bloodstream is usually broken into short pieces. The technology can also detect mutations in important genes such as TP53, a gene whose mutations are linked to higher-risk myeloma.

The bigger picture

Summing up the talk, Dr. Martínez López told the audience that "liquid biopsies in multiple myeloma are possible and yield complementary clinical information to conventional bone marrow biopsies." 

The main physical limitation of liquid biopsies, he noted, remains the small amount of cancer cells and DNA fragments available when disease levels are very low. But advances in ultra-sensitive testing and multimodal approaches, which combine several types of analysis, are beginning to overcome that hurdle. 

Dr. Martínez López urged the myeloma community to include these tools in clinical trials so that stronger evidence can be built for their use in everyday care.