Antibody-drug conjugates are a new kind of targeted treatment for multiple myeloma. They deliver powerful cancer-killing drugs straight to myeloma cells, and they help your own immune system attack the cancer. It's a more precise way to treat your cancer with medicine without harming healthy cells.
Multiple myeloma has become easier to treat thanks to new medications, but it's still not curable. Over time, the cancer often becomes resistant to treatment. Each new treatment produces a shorter and shorter response.
An antibody-drug conjugate could be an option if you have stopped responding to treatment.
Belantamab mafodotin (BLENREP) was the first antibody-drug conjugate to be FDA-approved for multiple myeloma. In October 2022, the FDA also approved a second antibody-drug conjugate, teclistamab-cqyv(Tecvayli), for the treatment of multiple myeloma.
How Do Antibody-Drug Conjugates Work?
Antibody-drug conjugates are like guided missiles. They contain two parts. One is a protein called an antibody. Attached to the antibody is an anti-cancer drug, which is sometimes called the "warhead."
The antibody seeks out and attaches to a matching protein called an antigen that is on the surface of myeloma cells, but is less common on healthy cells. Once attached, the antibody releases a high dose of cancer-killing medicine straight into the cancer cell. The medicine destroys the cancer without harming nearby healthy cells.
B-cell maturation antigen (BCMA) is the most common target used to treat multiple myeloma today. Belantamab mafodotin and teclistamab-cqyv (Tecvayli) are anti-BCMA treatments. They bind to BCMA, which is on the surface of multiple myeloma cells and some normal immune cells called B-lymphocytes.
Once they are inside the cancer cell, they release a microtubule inhibitor which blocks structures that help the cell work, which causes the cell to die.
Antibody-drug conjugates that work against other types of antigens are in clinical trials.
Who Can It Help?
Antibody-drug conjugates are for people whose multiple myeloma hasn't improved with other treatments or has come back after they've tried a few different treatments.
To be a good candidate for an antibody-drug conjugate, you need to have taken at least four of these immunotherapy medicines first:
- Monoclonal antibodies like daratumumab (Darzalex) or isatuximab (Sarclisa)
- Proteasome inhibitors like bortezomib (Velcade), carfilzomib (Kyprolis), or ixazomib (Ninlaro)
- Immunomodulating drugs such as lenalidomide (Revlimid), pomalidomide (Pomalyst), or thalidomide (Thalomid).
One study showed that belantamab mafodotin also helped people who'd had high-dose chemotherapy and a stem cell transplant as a first treatment for their multiple myeloma.
Researchers are looking at whether adding antibody-drug conjugates to other cancer drugs could treat multiple myeloma earlier in the course of the disease, soon after people are diagnosed.
How Do You Get It?
Belantamab mafodotin is a medicine that goes into your vein. The BLENREP IV takes 30 minutes. You get this treatment once every 3 weeks until it stops working and your cancer starts to progress again.
Teclistamab-cqyv is a shot that is given just under the skin every week.
What Are the Benefits?
A study called DREAMM-2 looked at the effects of belantamab mafodotin in nearly 100 people with multiple myeloma whose cancer didn't respond or came back after other treatments. About 1 out of 3 people who got belantamab mafodotin had at least some improvement in their cancer. The overall response rate for patients getting teclistamab-cqyv was over 60%.
Antibody-drug conjugates are called "off-the-shelf" treatments. They're not made specifically for you, like CAR T-cell therapy. Anyone can take them, which makes them easier for cancer centers to use.
What Are the Risks?
Antibody-drug conjugates prevent some side effects of chemotherapy because they target cancer cells instead of randomly killing healthy cells too. But this treatment does have some possible side effects. It's important to see a specialist who understands how to use antibody-drug conjugates.
One of the most common side effects of belantamab mafodotin is damage to the cornea, the clear outer surface of the eye. This damage can cause symptoms like:
- Vision changes and sometimes vision loss
- A sore called an ulcer on the cornea
- Blurred vision
- Dry eyes
- Low white blood cells and platelets – the blood cells that stop bleeding
Because of the risk to the cornea, belantamab mafodotin carries a “black box” warning – the FDA's strictest warning. You can only get belantamab mafodotin through a program called BLENREP Risk Evaluation and Mitigation Strategies (REMS).
The program will closely monitor you for side effects before and while you take belantamab mafodotin. You'll get an eye exam about 3 weeks before your first dose, before each dose, and if you have any vision symptoms. Also expect eye exams a week after you get each dose and 2 weeks before the next dose.
Use preservative-free eyedrops to relieve any dryness. Don't use contact lenses while you're on this treatment without first checking with your eye doctor.
Other possible side effects of belantamab mafodotin include:
Belantamab mafodotin can be dangerous to an unborn baby. Your doctor can talk to you about using birth control before you start taking this medicine.
Teclistamab-cqyv also carries a "black box" warning because it can cause a life-threatening or fatal reaction called cytokine release syndrome (CRS) and for its possible toxic effects on the nervous system. Medications are given before the dose of teclistamab-cqyv to help protect against these reactions. It is also only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Tecvayli REMS.
Is an Antibody-Drug Conjugate Right for Me?
If you have tried at least four other treatments for multiple myeloma but they haven't worked or your cancer has come back, an antibody-drug conjugate might be an option. Clinical trials are underway. Enrolling in one of these studies might give you access to a new treatment before it's available to everyone else.
Ask your doctor whether one of these studies might be right for you. Make sure you understand the possible risks and benefits of the treatment before you enroll in any study.
