Anti-CD38 antibodies are a type of immunotherapy used to treat multiple myeloma (MM). These medicines help your immune system find and damage myeloma cells. They're often used early in treatment as part of a combination plan (called a regimen).
Below, we'll walk through how anti-CD38 antibodies work and what to expect during treatment. This can help you have informed conversations with your care team. Treatment works best when it's tailored to your overall health and what matters most to you.
What Are Anti-CD38 Antibodies for Myeloma?
Anti-CD38 antibodies are lab-made antibodies (immune proteins) used to activate your immune system to kill myeloma cells.
How do anti-CD38 antibodies work?
Myeloma cells carry a protein on their surface called CD38. Anti-CD38 antibodies find this marker and stick to it.
Once these medicines attach to the CD38 protein, they act like a signal flare. This helps your immune system know which cells don't belong – it targets and kills them.
Another way to think about it: Your immune system already knows how to destroy harmful cells. Cancer becomes a problem when it blends in. Anti-CD38 antibodies help unmask myeloma cells so your immune system can better do its job and kill the cancer cells.
Together with other medicines, these medicines help:
- Identify myeloma cells
- Bring immune cells together to attack the cancer
- Help trigger cancer cell death
- Lower the number of myeloma cells over time
Right now, there are two approved anti-CD38 antibodies used to treat multiple myeloma:
Doctors usually combine three or four medicines to target myeloma in different ways. For example, you might get an anti-CD38 antibody with a proteasome inhibitor, a steroid, and sometimes an immunomodulatory drug (IMiD).
Side Effects and Safety of Anti-CD38 Antibodies
Most people handle anti-CD38 antibodies well. Still, these medicines affect your immune system. Specific side effects may vary based on which one you take, but here are some shared ones to know about.
Infusion reactions
You may have an allergic or allergy-type reaction during or shortly after a dose, especially with early treatments.
Symptoms may include:
- Shortness of breath
- Cough or chest tightness
- Runny or stuffy nose
- Throat problems, like irritation or tightness
- Dizziness
- Rash or itching
To lower the chances of a reaction, your care team will give you medications ahead of time. This cocktail often includes a steroid, antihistamines, and acetaminophen. With these pre-meds, most reactions are mild to moderate. Your care team will watch you closely during treatment.
Infection risk
Anti-CD38 antibodies can weaken parts of your immune system, making it harder to fight germs. This can leave you open to things like bacteria and viruses, especially the kind that settle into your nose, sinuses, throat, or chest.
To protect you, your doctor may:
- Prescribe antiviral medicine, like the kind that prevents shingles
- Suggest you get vaccines, such as flu or pneumonia shots
- Add antibiotics if your white blood cell count drops
- Use intravenous immunoglobulin (IVIG) if your immune protein levels get too low
These steps can lower your risk, but infections can still be serious. Call your care team right away if you get a fever that reaches 100.4 F or higher.
Hepatitis B reactivation
If you've had hepatitis B in the past, anti-CD38 antibodies can cause the virus to become active again. This is why doctors screen everyone for hepatitis B before treatment. If you test positive for prior hepatitis B, your doctor may give you an antiviral medicine to prevent the virus from flaring during therapy.
Low blood counts
These drugs can also lower cell counts like your white blood cells, red blood cells, and platelets. This is often mild but can make the following more likely:
- Infections, including serious ones like pneumonia
- Tiredness or shortness of breath (from anemia)
- Easy bleeding or bruising
Your doctor will check your blood counts often, usually once a week if you're early in treatment. If blood cell counts drop too low, your care team may:
- Adjust doses
- Pause treatment
- Add supportive medicines
You and your cancer care team will work together to manage side effects, adjust medication schedules, and prevent complications.
What Is Daratumumab (Darzalex, Darzalex Faspro)?
Daratumumab was the first anti-CD38 monoclonal antibody approved to treat multiple myeloma. Because it's been used the longest, doctors have a lot of experience with it. It's now a key part of many myeloma treatment plans, whether you're newly diagnosed or your cancer has come back (relapsed).
How daratumumab works
Once attached to the CD38 protein, daratumumab helps damage cancer cells in several ways at once. Daratumumab can:
- Mark myeloma cells so immune cells can destroy them
- Help trigger immune reactions that break apart cancer cells
- Block signals that help myeloma cells survive
Because it's highly targeted, it mainly affects cells that carry CD38.
How you take daratumumab
You may see daratumumab listed by its brand names: Darzalex and Darzalex Faspro. Both forms have the same medicine, but the main difference is how they're given.
- Darzalex: an IV infusion that takes several hours
- Darzalex Faspro: a shot under the skin that takes just a few minutes
The shot also contains an enzyme called hyaluronidase to help the medicine work under the skin. It's now more common because the shot is faster and less likely to cause a reaction.
Early visits may be longer at first because your care team needs to watch for reactions. Over time, appointments usually become shorter and more predictable. Many people don't need extra monitoring after the first few doses if they don't have a reaction.
What research shows
Large clinical trials have shown that adding daratumumab to standard multiple myeloma treatments helps people live longer without their cancer getting worse (called progression-free survival). In some studies, it's also been linked to longer overall survival and a longer-lasting response. These benefits are seen across many age groups and risk levels.
Side effects and safety
In addition to the shared risks listed above, daratumumab can cause problems with blood-typing tests. This matters if you ever need a transfusion. Your doctor will note daratumumab use in your medical records.
In addition to the class-wide cautions mentioned above, your care team may take extra steps or use caution if you:
- Have hepatitis B or had it in the past
- Had a severe allergic reaction to daratumumab in the past
Your cancer doctor will weigh the pros and cons of treatment and adjust your plan if needed. This may include extra monitoring or supportive care.
What Is Isatuximab (Sarclisa)?
Isatuximab is another anti-CD38 antibody used to treat multiple myeloma. You may also hear it called by its brand name, Sarclisa. Like daratumumab, it targets the CD38 protein on myeloma cells and helps your immune system better target cancer cells.
Doctors often use isatuximab for relapsed or refractory myeloma, meaning you've already tried another treatment that hasn't worked or your cancer has come back. It's also approved if you've been newly diagnosed and aren't able to get an autologous stem cell transplant.
Isatuximab is always used with other medicines as part of a combination treatment plan. It's often paired with proteasome inhibitors and steroids.
How you take isatuximab
You get isatuximab through a vein as an IV infusion. You usually get treatment at a clinic every week or two, depending on where you are in your treatment cycle.
What research shows
Clinical trials have shown that adding isatuximab to standard multiple myeloma treatments can help slow disease progression and lead to longer-lasting responses for some people.
Much of the early research focused on people with relapsed or refractory myeloma, where isatuximab improved outcomes when added to other medicines. More recent studies have also shown benefits for newly diagnosed people with multiple myeloma who can't get a stem cell transplant.
These benefits have been seen across different age groups, including older adults, which is why isatuximab has become an important option in combination treatment plans.
Side effects and safety
Most people handle isatuximab well, especially when side effects are watched closely and addressed early. But there are a few safety issues that are more specific to this medicine or the combinations it's commonly used with.
When isatuximab is paired with carfilzomib (Kyprolis), heart-related side effects may be more likely. Your care team may check heart function before and during treatment and adjust your therapy if needed.
In studies, a small number of people developed a second cancer while taking isatuximab. The overall risk appears low, but your care team will give you routine cancer screenings.
Isatuximab can also interfere with certain lab tests, including blood typing and tests used to track myeloma proteins. Be sure to tell any health care provider or blood bank that you're taking this medicine.
Cost and Insurance Coverage
The costs of daratumumab and isatuximab vary by dose and schedule. Call your insurance provider to ask about your out-of-pocket costs.
The companies that make these medicines may offer help, including
- Copay assistance programs
- Support for people with commercial insurance
- Help for those who are uninsured or underinsured
Patient support programs include Darzalex withME (for Darzalex and Darzalex Faspro) and careAssist (for Sarclisa). Visit the program website or ask your care team how to apply.
What Caregivers Should Know
Care partners play an important role in helping people with multiple myeloma stay on therapy and manage side effects.
You can help by:
- Tracking infusion or injection schedules, especially early on
- Planning for longer clinic visits during early doses
- Helping with medication timing, such as steroids taken before and after therapy
- Keeping notes on symptoms to share with the care team
- Watching for breathing changes, fever, or signs of infection
Don't brush off a higher temperature. Even a low-grade fever is something to take seriously, and it's always safer to call the care team than wait.
Cancer treatment can be physically and emotionally taxing at first, but many people settle into a more predictable routine after the first few cycles. If your loved one has trouble adjusting, encourage them to talk to someone. Many cancer centers have counselors or mental health professionals as part of the care team.
5 Things to Consider When Choosing a Treatment
Both anti-CD38 antibodies have been shown to help treat multiple myeloma. The best choice is usually about fit, not right versus wrong. The goal is finding the option that works best for your health, past treatment, and daily life.
Here are five things to think about:
Where you are in treatment. Some anti-CD38 antibodies are used more often at diagnosis, while others are common when cancer comes back. Your past treatments matter, and so does how your disease has behaved so far. Ask your doctor which option makes the most sense based on your situation.
How the medicine is given. Daratumumab with hyaluronidase can be given as a shot under the skin, or daratumumab through an IV infusion. Isatuximab is usually given through an IV infusion. The route can affect how long clinic visits last and how often you need treatment.
Your other health conditions. Heart disease, frequent infections, nerve problems, or kidney issues can all affect which drug and combination may be safest for you. That's why your doctor looks at your full medical history, not just your myeloma, when helping choose a treatment.
Side effects. All anti-CD38 antibodies affect the immune system, but side effects can vary depending on your body and the other medicines in your treatment plan. This is why two people on similar medicines can have different experiences. Your doctor will help weigh the pros and cons.
Your long-term plan. Multiple myeloma usually needs ongoing treatment. The choice you make now can shape what comes next, including maintenance therapy or future options if the cancer changes. Ask your doctor how today's treatment fits into your next steps.
Show Sources
SOURCES:
Brandon Blue, MD, hematology oncology, Moffitt Cancer Center, Tampa, Florida.
Natalia Neparidze, MD, associate professor, internal medicine (hematology); research leader, myeloma program, hematology, Yale School of Medicine, New Haven, Connecticut.
Hematologic Malignancies: "Current and Future Directions of Immunotherapies in Multiple Myeloma."
UpToDate: "Multiple myeloma: Administration considerations for common therapies," "Multiple myeloma: Initial treatment."
American Cancer Society: "Drug Therapy for Multiple Myeloma."
Memorial Sloan Kettering Cancer Center: "Immunotherapy & CAR T Cell Therapy for Multiple Myeloma."
FDA: "Sarclisa (isatuximab-irfc)," "Darzalex (daratumumab)," "Darzalex Faspro (Daratumumab and hyaluronidase-fihj)."
International Myeloma Foundation: "Using Immune Therapy to Fight Multiple Myeloma," "Darzalex (daratumumab)," "Managing Myeloma Symptoms: Infection Prevention, Bone Health, Kidney Care & Side Effect Management."
Blood Advances: "Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX."
The New England Journal of Medicine: "Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma."