Immune and myeloma cell surface-directed antibody therapies, or cellular therapies 

Bispecific Antibodies (also known as bispecifics, or BsAbs)

Bispecific antibodies (also known as bispecifics, or BsAbs) are an immunotherapy (immune cell therapy) showing promising clinical trial results. Bispecifics, as the name suggests, bind to two different types of cells. You can think of bispecifics as having two arms. One arm attaches to the myeloma cell. The other arm binds to an immune cell (a T cell or a Natural Killer Cell) to allow for that immune cell to attack the myeloma cell directly. This dual attack is more effective at helping the immune system to find and kill the myeloma cells. 

Some of the binding targets for bispecific antibodies are BCMA, CD38, CD138, FcRH5,and GPRC5D. (See a discussion of some of these at Emerging Therapies).

Bispecifics are being studied in many phases of clinical trials, including for relapsed/refractory and high-risk myeloma. Some important points to know about bispecific therapies include:

• Patients who may not be eligible for CAR T-cell therapy may be eligible for bispecific therapies. 
• Bispecifics do not need to be individualized or engineered, and they can have a variety of targets. Unlike CAR T Therapy, there is less delay in starting bispecific therapy as it is considered an “off-the-shelf” medication. Also unlike CAR T, bispecifics are not considered to be a “one-and-done” therapy. Rather, they are given on a continued schedule.
• Some bispecifics are given in a “step-up” dosing to reduce initial infusion reactions. Some hospitals/clinics may require hospitalization for initial dosing.
• Toxicity management: Bispecifics have been found to have manageable toxicities and fewer side effects than other newer immunotherapies. However, ongoing monitoring for infection is very important.

Overall, bispecifics are an exciting and important new therapy. See TECVAYLI™ (teclistamab-cqyv), the first bispecific approved for use in myeloma, as an example. Additional bispecifics are being evaluated in clinical trials. It is expected that in the coming months and years. more bispecfics with different targets will become available. 

Trispecific Antibodies

Trispecific antibodies are an additional type of immunotherapy currently in the early stages of research. Similar to bispecifics, you can think of trispecific antibodies as having multiple arms – in this case, three arms. Two arms bind to a myeloma cell, and one engages the immune system by binding to an immune cell (a T cell or Natural Killer cell). Alternatively, one arm may attach to a myeloma cell while the other two bind to the immune cells.  

One trispecific treatment currently under development targets BCMA, CD38, and T cells¹. Researchers hope that by having multiple targets, trispecifics will be even more effective against myeloma than bispecifics². 
 

Bispecific T-cell Engagers

Bispecific T-cell engagers (BiTEs®) are a specific type of bispecific antibody. Like other immunotherapies, bispecific T-cell engagers help your immune system to attack the myeloma cells. Bispecific T-cell engagers damage and destroy myeloma by bringing T cells close to the myeloma cells.  Bispecific T-cell engagers also help build immunologic memory, meaning your immune system can more easily find and recognize myeloma cells. 

Bispecific T-cell engagers are being studied as a single therapy (monotherapy) and in combination with other treatments.  

There are several advantages to using bispecific T-cell engagers in the treatment of myeloma. Similar to other bispecifics, bispecific T-cell engagers do not have a long manufacturing time and can be readily available to patients without delay. In addition, bispecific T-cell engagers can target myeloma cells that hide from our immune system.