Antibody therapy clears residual multiple myeloma in early trial

Antibody therapy clears residual multiple myeloma in early trial

Treatment with antibody therapy directed against immune and cancer cells eliminates remaining traces of blood cell cancer multiple myeloma. This is according to preliminary results of a clinical trial conducted by researchers at the Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. The results will be presented at the American Society of Hematology (ASH) Annual Meeting in Orlando on December 6, 2025.

None of the 18 patients who completed up to six cycles of treatment with the antibody linvoseltamab had detectable disease in high-sensitivity tests. This preliminary success suggests that linvoseltamab, a bispecific antibody, could allow patients to avoid bone marrow transplants, which require intensive, highly effective chemotherapy. It also points to the long-term possibility of improving patients' chances against this disease.

Lead researcher Dickran Kazandjian, MD, a Sylvester physician and professor in the Myeloma Division at the Miller School, conducted the research in collaboration with C. Ola Landgren, MD, Ph.D., director of the Sylvester Myeloma Institute, and will present the updated results at ASH.

These patients received modern and effective treatment beforehand that eliminated 90% of their tumor. Normally, such patients would receive high-dose chemotherapy and a transplant. Instead, we treat them with the drug linvoseltamab.”

Dickran Kazandjian, MD, a Sylvester physician and professor, Myeloma Division, Miller School

Landgren called the results so far "extremely impressive" and said the disappearance of the remaining myeloma cells bodes well for patients' future.

“Based on my experience, I would predict that after such a good response after such a short period of time, the disease could most likely go away for many years,” he said. "Could it never happen again in some patients? I would say it's possible."

Multiple myeloma is caused by antibody-producing immune cells called plasma cells. These cancer cells accumulate, disrupt normal blood cells and cause damage. There is no established cure. The US National Cancer Institute's Surveillance, Epidemiology, and End Results Program estimates that more than 192,000 Americans were living with the disease in 2022 and 36,000 new cases will be diagnosed that year.

Currently, most newly diagnosed multiple myeloma patients receive a combination of three or four medications. In some cases, this therapy destroys the myeloma cells, but sometimes the cancer persists. These traces of myeloma may occur in such small quantities that they are not visible on standard bone marrow tests.

To find tiny amounts of cancer, Sylvester doctors analyze bone marrow biopsies using a test that detects genetic sequences associated with the cancer. The test is sensitive enough to identify a single cancer cell from a million normal cells.

Oncologists call these few remaining myeloma cells minimal residual disease, or MRD. According to Landgren, who pioneered the use of MRD as an indicator of effectiveness in evaluating experimental therapies, patients who test MRD negative can expect to live years longer without their cancer returning than patients who test positive for MRD.

For many years, patients with residual disease (who are MRD positive) typically receive effective, high-dose chemotherapy after completing combination therapy. Although this chemotherapy aims to wipe out the remaining myeloma cells, it causes significant side effects. To make this approach possible, patients receive a transplant of their own blood-forming stem cells from their bone marrow the next day. It is a “pretty brutal therapy that was first introduced in Great Britain in 1983,” says Landgren. Unfortunately, in most cases myeloma will come back at some point.

The study, a Phase 2 clinical trial conducted in Sylvester and its satellite sites in Coral Gables and Deerfield Beach, has so far enrolled 25 patients who tested positive for MRD after completing combination therapy. These participants will receive four or six cycles of treatment with linvoseltamab.

While most therapeutic antibodies bind to a single target, bispecific antibodies bind to two. Linvoseltamab binds to CD3, a protein on the T cells that destroy cancer cells, and to a second target, BCMA, a protein on multiple myeloma cells. By bringing these two cell types into contact, the antibody strengthens the body's immune response to the cancer.

Some patients experienced side effects including a decrease in white blood cells, called neutropenia, and upper respiratory tract infections, but all of these events were within an acceptable safety profile, according to Kazandjian. Researchers took preventive measures to avoid triggering two potentially dangerous reactions, cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, that can occur with immunotherapies like this. However, these reactions have not yet occurred in any patient in this study. They then tested the patients' bone marrow for MRD using two independent and highly sensitive tests. No signs of illness were detected in any of the therapy graduates.

Based on its successes so far, Kazandjian hopes that linvoseltamab could offer patients more durable responses than transplants and potentially provide long-term control of the disease - a "functional cure."

"It's a bold claim, but we have to aim for the stars to move the field forward; that's what we're trying to do," he said.

Exploring this possibility requires further studies with many more participants who need to be followed over a period of years. The team is already taking a step in this direction. Based on the results so far, they are expanding registration to 50 participants.

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