Bispecific Therapies

How Bispecific Antibodies Work

Your T cells are powerful soldiers of the immune system, but they aren't always able to recognize and attack myeloma cells on their own. Bispecific antibodies act as a connector bridge. One "arm" of the bispecific antibody binds to a specific protein, or antigen, on the surface of a myeloma cell. Two common targets are B-cell maturation antigen (BCMA) and GPRC5D. The other "arm" of the antibody binds to an antigen called CD3, which is present on the surface of your T cells.

The bispecific antibody activates the T cell to release cytotoxic granules, which destroy the myeloma cells. Monoclonal antibodies, such as daratumumab, recruit immune cells to destroy myeloma cells. However, in relapsed or refractory myeloma, monoclonal antibodies may no longer be effective. Bispecific antibodies actively direct T cells to attack. The result is a highly targeted immune response that can be effective even in patients with a history of extensive prior treatment.

FDA-Approved Bispecific Therapies for Multiple Myeloma

The FDA has approved key bispecific antibodies for the treatment of multiple myeloma:

• Tecvayli® (teclistamab): This agent targets B-cell maturation antigen (BCMA). It is recommended for use after at least four prior lines of therapy. There are ongoing studies to confirm the clinical benefit of TECVAYLI®.
• Elrexfio® (elranatamab): This also targets BCMA and has shown significant effectiveness. In the MagnetisMM-3 study, the overall response rate (ORR) for patients on ELREXFIO was 61.0%.
• Talvey® (talquetamab): This therapy targets the GPRC5D protein. It offers an alternative for patients who may not have responded to BCMA-targeted therapies.
• Lynozyfic™(linvoseltamab-gcpt): This therapy targets B-cell maturation antigen (BCMA) and CD3 antigen on the surface of the patient’s T cells.

Tecvayli, Elrexfio, and Talvey are typically administered as a subcutaneous injection under the skin, usually in the arm, abdomen, or thigh. Lynozfic is administered intravenously.

Who Is Eligible for Bispecific Antibody Therapy for Myeloma?

The FDA approves bispecific antibodies for adults with multiple myeloma who have experienced a recurrence after at least four prior treatments, including:

• A proteasome inhibitor (like Velcade® or Kyprolis®).
• An immunomodulatory agent (like Revlimid® or Pomalyst®).
• An anti-CD38 monoclonal antibody (like Darzalex®).

Bispecifics offer a powerful alternative for patients unable to wait for CAR T-cell manufacturing due to rapid disease progression or ineligibility. Patients must have acceptable organ function and a stable health status to manage the potential side effects.

Additionally, in December 2025, the FDA granted breakthrough therapy designation for the use of Tecvayli in combination with Darzalex Faspro® (daratumumab plus hyaluronidase-fihj) as a second-line treatment for patients with RRMM. Second-line treatment refers to the next course of therapy used after the patient receives initial frontline therapy.

The Bispecific Therapies Treatment Roadmap

Following a defined treatment roadmap promotes better outcomes and safer administration:

1. Your care team will assess your eligibility for outpatient treatment with bispecific antibodies.
2. A multidisciplinary team develops a treatment plan and safety protocols to monitor and address any side effects.
3. You’ll begin with step-up dosing often in a hospital or specialized outpatient setting. You will receive two or three smaller doses over the first week, followed by the first full treatment dose.
4. Once tolerated, you will transition to an outpatient schedule of weekly or bi-weekly injections.
5. Ongoing monitoring ensures a quick response if side effects develop.

Patients continue to receive the drug as long as it keeps the myeloma in check and side effects remain manageable. Upon starting therapy, you will receive a wallet card that identifies you as a patient receiving bispecific antibody treatment. You should carry this with you at all times, as it provides critical information for any medical professional in case of an emergency.  

Potential Side Effects of Bispecific Therapies for Myeloma

Bispecific antibodies work by activating the immune system, so common side effects are related to this immune response. It is crucial to report any new symptoms to your healthcare team. Your healthcare team is expertly trained to manage these risks:

• Cytokine release syndrome (CRS): This is the most common side effect. When T cells are activated, they release a surge of inflammatory proteins known as cytokines. CRS symptoms include fever, fatigue, headache, low blood pressure, and shortness of breath. It is generally temporary and treatable with medications like tocilizumab or steroids.
• Neurotoxicity (ICANS): Immune effector cell-associated neurotoxicity syndrome (ICANS) is a condition that affects the nervous system. Warning signs may include confusion, difficulty writing, tremors, or changes in speech.
• Infection risk: Bispecific therapies can temporarily suppress the function of immune cells, potentially increasing the risk of infection. Patients are often prescribed prophylactic antivirals and antibiotics to prevent infections.

Manage Multiple Myeloma With Bispecific Therapy 

The landscape of myeloma treatment is moving fast. Researchers are currently evaluating the use of bispecifics in earlier lines of therapy, potentially allowing patients access before they have exhausted four other options. The IMF is a proud partner in the effort to advance myeloma research, including through our Black Swan Research Initiative®, which is dedicated to finding a cure.

If you have questions about whether you are a candidate for these therapies or need help finding a treatment center, you are not alone. Contact the IMF InfoLine to speak with a nurse specialist who can provide personalized guidance and support.