There are currently four bispecific antibodies approved by the U.S. Food and Drug Administration (FDA) for the treatment of multiple myeloma, including teclistamab, elranatamab, linvoseltamab and talquetamab.
Since their FDA approvals, the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute has safely treated over 200 patients with bispecific antibodies for relapsed/refractory multiple myeloma. Bispecific antibodies represent 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.
“The use of novel immunotherapeutics in multiple myeloma treatment has grown exponentially in the last three years,” says Shonali Midha, MD. “This has largely been driven by the approval of bispecific antibodies.”
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, elranatamab, and linvoseltamab, for example, bind to an antigen called BCMA on the surface of myeloma cells and simultaneously 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.
Talquetamab binds to a different antigen on myeloma cells, called GPRC5D, and to CD3 on T cells.
Which patients are eligible to receive bispecific antibodies?
Bispecific antibody therapies are approved for adult patients with relapsed or refractory (non-responsive) multiple myeloma who have received at least four prior lines of treatment, 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.
Clinical trials are testing their efficacy as an early line of therapy and in various combinations with other myeloma therapies. Recently, one BCMA-directed bispecific antibody, teclistamab, was granted accelerated approval in combination with daratumumab in patients with relapsed or refractory multiple myeloma who have at received at least one prior line of therapy including an immunomodulatory agent.
Ask your Dana-Farber care team about these medicines or about participation in trials of these medicines in other scenarios.
How are bispecific antibodies given?
These drugs are given either as an injection under the skin (SC) or intravenously (IV) and administered initially on a “step-up” dosing schedule, followed by a set interval. Patients receive the first three doses, in gradually increasing amounts, either in the hospital or in the outpatient clinic. Once patients have received the full dose, the drug is continued at the set interval in the outpatient clinic.
After each step-up dose, patients must be closely monitored for side effects such as cytokine release syndrome, a rapid-forming inflammatory reaction. If these don’t arise, the next step-up dose is given. Step-up schedules vary slightly between the different medicines.
Patients who live or are temporarily staying within one hour of Dana-Farber’s Longwood Campus and who are deemed eligible by their treatment team may complete the step-up-dosing for these therapies as outpatients.
Patients who receive step-up dosing in the outpatient clinic are seen in the clinic daily and do not stay overnight, but they must have round-the-clock supervision by a caregiver. The patient and caregiver go home or to nearby short-term housing accommodations with detailed monitoring instructions as well as monitoring tools such as a thermometer, blood pressure cuff, blood oxygen meter, and a logbook.
In addition, they will receive a call from the nursing team within a few hours of the injection for a check-in. Should symptoms arise, the care team is ready to help the patient manage them at home, direct them to return to the clinic, or if necessary, to visit the Emergency Room or hospital.
The outpatient program has saved more than four days of hospitalization per patient on average from what is typically a seven- to nine-day hospitalization. Some patients have been able to avoid hospitalization altogether.
“We’re excited about being able to offer this as an outpatient option,” says Midha. “I think it’s more comfortable for patients, and it can hopefully increase access for patients for whom a week in the hospital would be difficult to manage.”
Patients who receive step-up dosing in the hospital can expect to stay in the hospital for about a week. After being discharged, patients receive the drug weekly in the clinic
Ask your care team to learn more about our Bispecific Outpatient Safe Step-up (BOSS) program and whether you may be eligible.
How effective is it?
In the trials that led to FDA approvals of all three medicines, more than 60% of patients who received the drug had a positive response. Between a third and a half of patients had a complete response, the disappearance of all signs of their cancer.
What are the most common side effects?
In clinical trials, 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 underway testing:
- Novel bispecific antibodies,
- Novel trispecific antibodies that target two myeloma or tumor antigens and CD33 on T cells at the same time,
- Bispecific antibodies in combination with other therapies,
Bispecific antibodies for the treatment of multiple myeloma precursor conditions or early disease.
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.
As an individual being followed, not having it, this is great news. After the trials are ended, will this drug be available to any patient who has been told they now have been diagnosed with this cancer?
Teclistamab is currently FDA-approved for patients whose diseased has progressed after four prior lines of therapy based on the completed Phase 1/Phase 2 trial of the medication. There are also several ongoing trials of this and similar bispecific antibody therapies in varying combinations and earlier lines of therapy. The results of these trials may alter the circumstances in which such medications are safely used in the future.