Newer Treatments for Newly Diagnosed Multiple Myeloma (MM)

Lenalidomide (Revlimid) and other IMiDs

Lenalidomide (Revlimid) is often the first IMiD you'll get. It's the key to most standard treatment plans for multiple myeloma.

A recent clinical trial showed that adding the daratumumab with hyaluronidase shot to a combined treatment may help newly diagnosed patients live longer without their multiple myeloma progressing. The combined treatment included bortezomib, lenalidomide, and dexamethasone.

Pomalidomide (Pomalyst) and thalidomide (Thalomid) are also IMiDs, but they aren't usually used first. Your doctor may suggest:

• Thalidomide if you have kidney disease, low blood cell counts, or if your myeloma has progressed. 
• Pomalidomide if your myeloma has come back or progressed.

Whatever you and your doctor choose, you'll likely start out getting three or four different medicines at once.

Medicines for early-stage myeloma treatment

Your doctor has lots of choices to design a treatment plan that works best for you. They can also add steroids like dexamethasone or a chemotherapy medication such as cyclophosphamide (Cytoxan, Neosar).

Here are the approved proteasome inhibitors and anti-CD38 antibodies that treat myeloma:

What Are Proteasome Inhibitors?

Proteasome inhibitors are targeted medications used to treat multiple myeloma. Doctors often include them early because they directly weaken myeloma cells and help other treatments work better.

Protein cleanup

These inhibitors can break basic cell machinery that myeloma cells need to survive. That includes protein cleanup, a job handled by the proteasome. When that system gets blocked (inhibited), cancer cells struggle to grow and can die.

Think of it like a factory that becomes overloaded with waste. After too much waste builds up, the whole system shuts down.

Aids other treatments

Proteasome inhibitors stop myeloma cells from getting rid of certain proteins, which can build up to weaken and kill the cancer cells. This also puts extra stress on the cancer cells, helping immune-based therapies to work better.

That's why proteasome inhibitors are often grouped with immunotherapies in treatment plans – even though they aren't the same type of medicine. There are three main proteasome inhibitors approved to treat multiple myeloma.

Bortezomib (Velcade)

The first proteasome inhibitor approved to treat multiple myeloma, bortezomib, remains widely used at many treatment stages. You may get bortezomib with lenalidomide (IMid) and dexamethasone (a steroid), or some other combination.

You usually get bortezomib as a shot just under the skin. Less often, you'll get this protease inhibitor through an IV (in a vein). Treatment is typically once or twice a week during a set cycle, often part of a combination regimen.

Carfilzomib (Kyprolis)

A newer proteasome inhibitor, carfilzomib, binds more tightly to proteasomes. You may also get this medicine with lenalidomide and dexamethasone.

Because of its stronger effect, your doctor may suggest it if:

• You have higher-risk disease
• You have fast-growing disease
• Bortezomib stops working

You'll get carfilzomib through an IV. Schedules vary, but common treatment plans include once-weekly dosing at a higher dose or twice-weekly at lower doses.

What Are Anti-CD38 Antibodies?

Anti-CD38 antibodies are an immunotherapy used in multiple myeloma. The medicine attaches to the many CD38 proteins found in high amounts on myeloma cells.

After the medicine attaches to the CD38 protein, it marks the myeloma cell for your immune system to find and destroy. Anti-CD38 antibodies are often used for early myeloma treatment along with proteasome inhibitors and steroids.

There are two commonly used anti-CD38 antibody medications approved to treat multiple myeloma.

Daratumumab (Darzalex, Darzalex Faspro)

Daratumumab is widely used across different stages of treatment. You can get daratumumab (Darzalex) through an IV infusion or daratumumab with hyaluronidase (Darzalex Faspro) as a shot under the skin.

Dosing usually starts weekly, then moves to every other week and later to monthly. Today, many people get the under-the-skin form. It's quicker to give and tends to cause fewer treatment-day reactions.

Isatuximab (Sarclisa)

Isatuximab can also attach to the CD38 protein and signal your immune system to find and kill myeloma cells. It's currently given through an IV infusion, but a shot is on the way.

Doses usually start weekly for the first month or two, then go to every two weeks. You may also get it monthly.

Isatuximab is approved for some people who are newly diagnosed and not planning to have a stem cell transplant. But it's commonly used when myeloma has come back after an earlier treatment.

The Role of Combined Medicines in Multiple Myeloma

Myeloma cells are good at changing. When a treatment stops one pathway for growth, the cancer cells sometimes find a way around it. So your doctor will likely use more than one medicine at a time.

Combining medications can help lower your chance that the myeloma cells will escape treatment. You can think of it like a lock-and-key problem.

Myeloma cell locks and medication keys

Usually, myeloma cells rely on many locks to grow, like the CD38 protein. Medication acts like a key, "unlocking" the myeloma cell to weaken and destroy it.

But myeloma cells can find ways to grow without the lock, and the antibody "key" stops working. Using more than one medication key at the same time makes it harder for your cancer cells to find a way around all the locks and keep growing.

Combining medications for myeloma

Each medicine in your regimen also plays a different role. Some damage myeloma cells directly. Others make it easier for your immune system to find and destroy myeloma cells. Together, weaker myeloma cells and targeted immunotherapy can lead to deeper, more durable responses than using a single medicine alone.

More flexible treatment plans

Combination therapy also gives you and your doctor more flexibility. Rather than needing a higher dose of one medicine, you may get:

• A balanced regimen designed to control the cancer while managing side effects
• An adjusted regimen, without changing the entire plan,  if one medicine causes problems or doesn't work as well

Tests to monitor progress

Throughout treatment, your doctors can track your progress and may do:

• Blood tests
• Imaging scans
• Medication adjustments
• Symptom check-ins

These ongoing activities help monitor and fine-tune your treatment to keep it working and as manageable as possible.

5 Things to Consider When Choosing Therapy

There isn't one treatment plan that works best for everyone. If you're just starting multiple myeloma treatment, your doctor can help.

They'll review treatment plan choices based on your health, your priorities, and how the cancer is behaving in your body. Before your next visit, here are five things to keep in mind:

Your options. Your doctor can walk you through which medicines make sense for you and why. Review proteasome inhibitors, anti-CD38 antibodies, or a mix of them. It'll help you learn the medicine names, how they're given, and how often you'll get treatment.

Possible side effects. All cancer treatments can come with side effects. Ask which ones are most common and matter most for you. Tell your doctor if you already have issues like nerve problems, heart disease, or kidney disease.

How treatment fits into your life. Some treatments can mean longer clinic visits, while others are just quick shots or pills you take at home. Think about your daily schedule, work, caregiving responsibilities, and how far you travel for care. Sharing what matters most can help your care team shape a plan that best fits your life.

Your longer-term plan. If a stem cell transplant is part of your care plan, your doctor will time treatment around your stem cell collection. Even without a transplant, most people stay on treatment in some form over time. Ask how your plan today will fit into what may come next.

Cost and coverage. Newer therapies can be expensive, but costs vary. Check with your insurance plan about coverage and out-of-pocket expenses. You may be able to get financial help through assistance programs. A financial counselor or social worker at your cancer center can help you explore options.