In 2022, the drug teclistamab became the first bispecific antibody to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma. Experts say the drug represents one of the most important advances in recent years against myeloma, a blood cancer diagnosed in more than 35,000 people in the United States each year.
What are bispecific antibodies and how do they work?
Antibodies are Y-shaped proteins that play a key role in the immune system. Produced in the millions, they’re each able to latch onto a particular disease-causing microbe, infected cell, or cancer cell. By binding to surface molecules called antigens, antibodies can either destroy these harmful microbes and cells or trigger an immune system attack on them.
Unlike standard antibodies, which link to just one antigen, bispecific antibodies can attach to two at a time. Teclistamab, for example, binds to an antigen called BCMA on the surface of myeloma cells and to a surface marker called CD3 on immune system T cells. This brings the myeloma and T cells in closer proximity to each other, which activates the T cells and primes them to kill the myeloma cells.
Which patients are eligible to receive teclistamab?
As of March 2023, teclistamab is approved for adult patients with relapsed or refractory (non-responsive) multiple myeloma who have received at least four prior treatments, including a proteasome inhibitor (which prevents cancer cells from breaking down unneeded proteins), an immunomodulatory agent (which stimulates the immune system), and an antibody agent that binds to the CD38 protein on myeloma cells. Ask your Dana-Farber care team about participation in these trials.
How is teclistamab given?
The drug is given as an injection under the skin and is administered on a “step-up” dosing schedule. Patients receive the first three doses, in gradually increasing amounts, while in the hospital. After each dose, patients are closely monitored for side effects such as cytokine release syndrome, a rapid-forming inflammatory reaction. If these don’t arise within 48 hours, the next dose is given. Patients who don’t develop side effects are in the hospital for about a week. After being discharged, patients receive the drug weekly in the clinic.
How effective is it?
In the phase II clinical trial that led to the approval of teclistamab by the FDA, more that 60% of patients who received the drug had a positive response. Almost 30% had a complete response, the disappearance of all signs of their cancer.
What are the most common side effects?
In the phase II trial, called MajesTEC-1, the most common adverse effects were fever, cytokine release syndrome, low blood counts, musculoskeletal pain, fatigue, upper respiratory tract infection, and nausea. Ask your care team about how common side effects are managed or protected against.
Are other bispecific antibodies being developed for myeloma?
Clinical trials are under way of several bispecific antibodies that, like teclistamab, target the BCMA antigen on myeloma cells. Others are being developed that target other myeloma cell antigens. Trials of bispecific antibodies in combination with other therapies are also in progress.
About the Medical Reviewer
Dr. Midha is a medical oncologist focused on the treatment of multiple myeloma and plasma cell disorders. She completed her internal medicine residency training at the University of South Florida in Tampa, FL., where she completed a Chief Residency year, and her hematology/oncology fellowship at Moffitt Cancer Center, Tampa, FL where she also served as Chief Fellow. She is board certified in internal medicine, hematology and medical oncology. She joined the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in 2021. She is an Instructor in Medicine at Harvard Medical School. Her clinical and research interests include further understanding high risk disease and studying the role of novel effective therapies including immunotherapy and cellular therapies in multiple myeloma.