[00:00]
Professor Hang Quach: Hello, everyone. I’m Professor Hang Quach from St Vincent’s Hospital Melbourne and the University of Melbourne.
It’s a privilege to be able to share with you some exciting new treatments for multiple myeloma as part of Myeloma Awareness Month. These treatments work by waking up your own immune system to fight multiple myeloma.
You may have heard of a new wave of immunotherapies called bispecific or trispecific antibodies, also known as T-cell engagers. They sound complicated, but the basic idea is quite simple. By the end of this talk, I hope these terms will feel much more familiar to you.
[00:38]
What is multiple myeloma?
Multiple myeloma is a cancer of plasma cells. Plasma cells normally produce antibodies to help us fight infections.
In myeloma, these cells grow out of control in the bone marrow and crowd out healthy blood-forming cells. They also produce abnormal proteins called paraproteins, M proteins or excess light chains, which can be detected in the blood.
While we currently have many effective treatments, multiple myeloma almost always returns after each line of therapy. That’s why we continue to develop new approaches. One of the most important advances that has changed the treatment landscape is immunotherapy. Here’s how it works.
[01:21]
For more than a century, we’ve known that the immune system is one of the most powerful tools we have against cancer. In healthy individuals, the immune system constantly monitors the body, recognising and eliminating cancer cells before they can grow and spread.
Under normal circumstances, when a cell becomes cancerous, specialised immune cells called antigen-presenting cells, or APCs, patrol the body. They detect abnormal cells, engulf them and process their proteins.
The APCs then present small fragments of these proteins to key immune command-centre cells called T cells.
[02:01]
Once T cells recognise the cancer-associated proteins, they become activated and launch a targeted immune response that destroys the cancer cells before they grow out of control.
This process, called immune surveillance, is one of the reasons many people with healthy immune systems never develop cancer.
When cancer does progress, it is often because this surveillance system breaks down. Cancer cells can release cytokines and other signalling molecules that interfere with the function of antigen-presenting cells. Instead of activating T cells, these signals suppress them, preventing an effective immune response.
[02:43]
This is where T-cell engagers come in.
What are T-cell engagers?
These T-cell engagers, also known as bispecific or trispecific antibodies, are specially designed antibodies that act like a bridge.
They are molecules with two or three binding ends. One end grabs onto an immune T cell, while another end grabs onto a myeloma cell. By physically bringing these two cells together, the T cell can clearly see the cancer cell and do its job, resulting in T-cell-mediated killing of the myeloma cell.
[03:20]
This is what it looks like under the microscope. The green cell on the left is a myeloma cell, and the blue cell on the right is a T cell.
The T-cell engager acts like a tiny molecular bridge, physically linking the T cell to the myeloma cell. You can’t see the engager here because it is far too small, but you can see its effect. It pulls the two cells tightly together.
Once connected, the T cell becomes activated and starts producing bright, multicoloured toxic packets. These are the weapons the T cell uses to attack.
The T cell delivers these toxins directly into the myeloma cell through a tight contact point called a synapse, leading to the destruction of the cancer cell.
In essence, the patient’s own immune T cells are killing their own myeloma cells. This all happens without the need for chemotherapy.
[04:12]
There are two broad groups of T-cell engagers.
The first generation are bispecific T-cell engagers. Bispecific means they bind to two targets: one on the myeloma cell and one on the T cell. This physically brings the immune cell into contact with the cancer cell.
These typically bind to BCMA on the myeloma cell and CD3 on the T cell.
The next generation are trispecific T-cell engagers. Instead of binding to two targets, they bind to three. Usually, two of these targets are on the myeloma cell and the third binds to the T cell.
This design links the T cell to the myeloma cell much more strongly and triggers cancer-cell killing more effectively.
[04:58]
Currently, there are three BCMA-targeted bispecific T-cell engagers approved for people with relapsed or refractory multiple myeloma around the world.
The one that will soon be reimbursed and accessible to Australians is elranatamab, with the trade name Elrexfio.
There is also teclistamab, with the trade name Tecvayli. This is approved by the Therapeutic Goods Administration and can be accessed in Australia, but it is not yet reimbursed through the Pharmaceutical Benefits Scheme as of February 2026.
The third agent, linvoseltamab, with the trade name Lynozyfic, is currently only available overseas.
All three show very similar outcomes, with response rates of approximately 60 to 70 per cent in heavily pre-treated patients. When responses occur, they typically last for more than two years.
[05:49]
There are also other bispecific T-cell engagers that target markers on myeloma cells other than BCMA.
One example is talquetamab, which targets a marker called GPRC5D on myeloma cells. It is TGA-approved in Australia but is not reimbursed through the PBS, so it is not routinely available right now.
Another is cevostamab, which targets FcRH5 on myeloma cells. It is very effective but is still being investigated in clinical trials.
Overall, these agents are similarly effective to BCMA-targeted bispecific antibodies, with response rates of approximately 50 to 70 per cent. Responses often last longer than one year.
[06:35]
What does treatment with a bispecific T-cell engager look like?
Treatment usually involves regular injections under the skin. Early on, we use smaller step-up doses and monitor patients closely, typically on days one, four and eight, although this can vary.
For the first one or two doses, patients may need to be admitted to hospital so that we can monitor for side effects, particularly cytokine release syndrome, or CRS, which we will discuss shortly.
Once patients are stable, treatment is usually given as an outpatient. It is quick and often does not require premedication after the first three doses.
Over time, the frequency may be reduced to every two to four weeks, or even less often, depending on the patient’s response.
[07:23]
Let’s talk briefly about some of the side effects you can expect.
Because these treatments activate the immune system, the most common side effects are immune-related. While they may look worrying on paper, they are generally very manageable, and many people are able to continue their normal activities of daily living.
The three main side effects are CRS, or cytokine release syndrome; ICANS, or immune effector cell-associated neurotoxicity syndrome; and infections.
[07:54]
CRS occurs in approximately 40 to 70 per cent of patients, usually during the first one or two step-up doses. It is typically mild and presents with fevers and sometimes low blood pressure requiring intravenous fluids. Oxygen support is rarely needed.
CRS can resolve on its own, but sometimes treatments such as tocilizumab or dexamethasone are required. These are medications that slow down the immune system.
ICANS is a neurological side effect related to immune activation. It is uncommon with bispecifics, occurring in fewer than five per cent of patients. When it does occur, it is usually mild and reversible.
[08:34]
Infections, unfortunately, are quite common. This is because myeloma itself suppresses immunity, and T-cell engagers that bind to BCMA can reduce normal antibody production.
These infections are generally manageable and tend to improve as myeloma comes under control and treatment frequency decreases.
Talquetamab is the bispecific T-cell engager I mentioned earlier that targets GPRC5D.
Because the same marker, GPRC5D, is also present on the skin and tongue, talquetamab has an additional set of side effects, such as taste changes, dry mouth, dry skin and nail changes. These usually improve over time and with ongoing treatment.
[09:23]
What’s on the horizon?
Undoubtedly, bispecific T-cell engagers have transformed the outlook for people living with multiple myeloma. But you’ll be glad to know it doesn’t stop there.
Rapid progress is still underway, and the next exciting developments are the trispecific T-cell engagers that we spoke about. These have the potential to significantly improve not only survival, but also quality of life for people living with myeloma, even more so than bispecific T-cell engagers.
[09:52]
Like the current bispecific antibodies, trispecifics are designed to bring a patient’s own T cells directly into contact with myeloma cells so that the T cells can attack the myeloma.
The key difference is that bispecifics bind to one myeloma-cell target and one T cell, whereas trispecifics bind to two targets on the myeloma cell at the same time, in addition to the T cell.
In doing so, trispecifics may capture more myeloma cells, bind to them more securely and reduce the chance of escape and relapse.
In addition, these second-generation T-cell engagers are engineered with a longer half-life, allowing for less frequent dosing. They are also designed to stimulate T cells more gently, which may lead to fewer immune-related side effects.
[10:44]
On the right-hand side are examples of three types of trispecific T-cell engagers that are currently in clinical development and are producing impressive results like we’ve never seen before.
These agents include ISB 2001, JNJ-5322, also called ramantamig, and another compound called IBI3003.
Early studies of these agents in heavily pre-treated patients have shown very promising response rates, ranging from 80 to nearly 100 per cent, with some responses lasting beyond 18 months and continuing in patients with end-stage disease.
These agents are still under clinical investigation and can be accessed through clinical trials at major hospitals in Australia.
[11:33]
In the last minute, I’d like to focus on something that is very important: your role as a patient.
As you start treatment with a bispecific T-cell engager, it is important to know what to expect and how to care for yourself.
For the first one or two doses, expect a short hospital admission for monitoring. After that, treatment follows a regular schedule over a longer period.
Supportive care, including immunoglobulin or antibody replacement therapy, may be used to help protect your immune system.
[12:05]
Infection prevention is crucial. You will likely be prescribed preventative medications, such as antivirals—for example, Valtrex—and antibiotics such as Bactrim. Sometimes, growth-factor injections may also be used to boost white blood cells when they are low.
Staying up to date with vaccinations, practising good hand hygiene and avoiding contact with people who are unwell are also important.
Try to stay well hydrated and eat nutritious meals. Look after your skin and keep it well moisturised, as it is one of the body’s most important barriers against infection.
[12:40]
Stay active and rest when needed.
You also need to lean on your support network, whether that is family, friends or the myeloma support network.
Write down your questions and always speak up if something doesn’t feel right. Remember, you are a crucial part of your own care team.
[13:02]
To close, I’d like to leave you with a message of hope—one I’ve had the privilege of seeing firsthand.
The pace of progress in treatment for multiple myeloma has never been faster.
Immune-based therapies, especially T-cell engagers, are transforming myeloma into a disease that can be controlled for longer periods, with better quality of life and more options at every stage.
Treatments that were once considered experimental are now becoming the standard of care, and what lies ahead is even more promising.
With continued research and ongoing advocacy from both clinicians and patients, the future for people living with multiple myeloma is brighter than ever.
Thank you for listening, and thank you for being part of this journey forward.
