Two decades ago, doctors had a limited toolkit for treating multiple myeloma. “Now there are about 15 different drugs that are approved for multiple myeloma,” says Hearn Jay Cho, MD, PhD, chief medical officer of the Multiple Myeloma Research Foundation and a clinical professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City.
These treatments, as well as new and developing therapies, have brightened the outlook for multiple myeloma patients. And while the disease is still considered incurable, these newer treatments and those still in the pipeline hold the promise of improved outlooks, longer periods of remission in patients, and maybe, for some, the possibility of a cure.
Immunotherapies for Multiple Myeloma
“The cells of your immune system that are best suited to kill cancer cells are called killer T cells,” Cho says. “These [immuno]therapies are designed to redirect T cells to kill myeloma cells – a broad category called T-cell redirection therapy.”
Because cancer cells grow abnormally among our regular cells, they are hard for our immune systems to find as something foreign the body needs to get rid of. Sometimes, these cancer cells change, or mutate, to evade detection – reversing the cancer-fighting abilities of immune cells. Other times, certain proteins on their surfaces turn off the cancer-fighting abilities of immune cells. But sometimes, they express proteins at high levels that our T cells could identify and eliminate – if only they knew how.
In multiple myeloma, one such targetable protein is called BCMA (B-cell maturation antigen). BCMA is a protein found on plasma cells that helps with their activation. These newer immunotherapies – CAR T-cell therapy and bispecific antibodies – target BCMA on the surface of myeloma cells.
“It's lucky to find that myeloma cells happen to express BCMA rather consistently and that patients can live even if the good BCMA-expressing cells – normal plasma cells – are knocked out. For other blood cancers such as acute myeloid leukemia (AML), finding a protein that meets both criteria has been quite difficult,” says Rahul Banerjee, MD, FACP, an assistant professor in the Clinical Research Division at the Fred Hutchinson Cancer Center in Seattle.
CAR T-cell therapy
Altering the immune system’s invader-fighting T cells is now a potent therapy for treating patients whose myeloma has come back, or relapsed, after remission. One such treatment is CAR T-cell therapy. “You take the T cells out of the patient, genetically modify them to force them to recognize the myeloma cells as foreign, and put them back into the patient,” Banerjee explains.
CAR T-cell therapy (CAR stands for chimeric antigen receptor) has been available for about five years. But until recently, CAR T was a last line of therapy for patients whose other treatments had failed. “Now, as soon as the first relapse, patients can get CAR T therapy for multiple myeloma,” Banerjee says.
The two types of CAR T-cell therapies that have been approved by the FDA for treatment of relapsed or refractory (not responding to treatment) multiple myeloma are:
- Idecabtagene vicleucel (Abecma)
- Ciltacabtagene autoleucel (Carvykti)
Research is going on to figure out whether some myeloma patients might benefit from CAR T rather than a stem cell transplant as a first line of treatment. In fact, clinical trials in progress at Fred Hutchinson and other institutions are testing CAR T-cell therapy on patients just diagnosed with myeloma, Banerjee says; the results are not yet available.
Bispecific antibodies (also called bispecific T-cell engagers, or BiTEs)
Bispecific antibodies are modified to act as a type of matchmaker that brings T cells and myeloma cells together to help T cells recognize and destroy the cancer.
“Antibodies typically have two sticky ends, but they usually recognize the same target,” Cho says. “With these engineered antibodies, each sticky end recognizes a distinct target. One end recognizes BCMA on the surface of myeloma cells. The other end sticks to something called CD3, which is on the T cell and one of the ‘on’ switches for T cells.” The end that sticks to the T cell flicks on a switch that activates the T cell to kill the invading myeloma cells.
The process works by forcing “the T cell to overrule all its logic and machinery and rules of operation and instead attack” the cell it is normally programmed to ignore, Banerjee explains.
This therapy is effective and works well in myeloma patients who’ve had several prior rounds of therapy and relapse. Researchers are studying whether bispecific antibody therapy can be given earlier, and preliminary results are promising: “The idea being that you move your best therapies closer to the front, and hopefully you get longer remissions,” Cho says.
Side Effects of Multiple Myeloma Immunotherapy
These are two powerful options for treating myeloma with immunotherapy, Cho says. “And I think the obvious question is, why aren’t we giving them to everybody all the time up front?” Both treatments have significant side effects, he says, and they also require patients to either travel to or be near a center or hospital that provides them.
And while BCMA is on the surface of myeloma cells, it’s also found on the surface of normal B cells. B cells create antibodies that fight off threats to your immune system. In immunotherapy, “there’s a dramatic reduction in the number of normal B cells in addition to myeloma cells. That reduces the amount of normal antibodies the body makes and results in vulnerability to infection. So that’s a significant side effect of both bispecific T-cell engagers and CAR T cells,” Cho explains.
Doctors do a lot to protect myeloma immunotherapy patients from infection. They give antibiotics and antiviral drugs preventively to ward off bacterial and viral infections. “And then we give them normal antibodies from other people to help supplement their immune system,” Cho says.
Both types of therapy stimulate a powerful immune response in your body, with fevers, low blood pressure, and other signs of infection present. Because of this, CAR T-cell therapy is given in hospitals. The therapy has been limited to major medical centers because of the specialized training, equipment, and health care providers needed to manage the procedure and its side effects. To get it, you may have to uproot yourself and your support system to stay near the treatment center for several weeks – but only once. “You’re in the hospital for two weeks, but after that, there’s no actual therapy. There’s a lot of supportive care, and you’ll still have to go to your doctor, but there’s no actual anticancer therapy,” Cho says.
In July 2025, the FDA eliminated its more rigorous safety measures from several forms of CAR T, including Abecma and Carvykti, which required patients to get the therapy at specially certified centers. Relaxing these rules will allow more health care facilities to provide these treatments.
Rarer side effects of CAR T-cell therapy include long-term neurologic symptoms similar to Parkinson’s disease, which have developed in about 5% of patients. A small number of patients have also had gut symptoms such as chronic diarrhea and inflammation similar to that in inflammatory bowel disease. A third rare but worrisome complication is the development of secondary blood cancers such as myelodysplastic syndrome and acute myelogenous leukemia. “That’s obviously a great concern because a lot of cancers and their therapies are associated with these secondary cancers,” Cho says.
However, just the short-term side effects of CAR T therapy can be unbearable for some patients – and the procedure doesn’t have long-term effects for every relapsed patient. The Multiple Myeloma Foundation’s Translational Research Umbrella (TRU) program has a goal to figure out which patients benefit from CAR T, which don’t, and why. The first phase will investigate CAR T, but researchers will eventually look at bispecific therapy, too.
What’s on the Horizon in Multiple Myeloma Research?
Researchers are trying to uncover information about changes in genes and cells that can lead to myeloma. Figuring out how the disease works may help them understand what types of treatment work best and which people are at a higher risk of getting the cancer or having their cancer get worse. Several clinical trials are investigating new uses and combinations of already-approved drugs and treatments for myeloma. The Multiple Myeloma Research Foundation, in partnership with academic medical centers and the makers of drugs for myeloma, is looking at new uses for existing drugs. “What we’re trying to do is find how to best use these approved or close-to-approved agents to make them most effective for myeloma patients. It’s a really important part of what we do as part of our research program,” Cho says.
Smoldering multiple myeloma (SMM) is a precancerous condition that can quickly turn into full-blown myeloma for some patients. It’s a condition doctors usually observe closely – twice-yearly MRIs and monthly bloodwork in some cases, Banerjee says. Doctors have long wondered whether “for these very high-risk patients who are on the cusp of myeloma, could we do something to lower that risk?” he adds.
A clinical trial was done at many centers, including Fred Hutchinson, looking at whether giving high-risk SMM patients a drug already approved for multiple myeloma, called daratumumab and hyaluronidase-fihj (Darzalex Faspro), would delay the start of myeloma. Early results show that patients on daratumumab and hyaluronidase-fihj have a lower risk of progressing to multiple myeloma, and their quality of life three months after their therapy was improved. “They feel better, and they live longer. It is very impressive that these patients who got early treatment actually did better,” Banerjee says. On Nov. 6, 2025, the FDA approved the use of daratumumab and hyaluronidase-fihj for adults with high-risk SMM.
Some other ways researchers are trying to improve myeloma treatments:
- Investigating personalized treatments tailored to a patient’s own genetic and immune system profile
- Using a type of therapy called precision medicine to find ways to fine-tune drugs to target genetic abnormalities in myeloma cells
- Doing clinical trials to see whether using more than one bispecific antibody will provide a longer remission than a single one or using them along with other drugs
- Finding ways to lessen side effects and produce safer, more effective, and more tolerable myeloma therapies
Long-Term Survival and the Potential for a Cure
With the prospect of enduring remission in some patients who have had emerging therapies such as CAR T-cell and bispecific antibodies, doctors are thinking about what a cure for multiple myeloma might look like. “The International Myeloma Working Group, which is a kind of ‘Who’s Who’ in myeloma across the world in terms of defining ‘what is myeloma,’ is actually planning to convene a panel next year defining cure in myeloma,” Banerjee says.
The group’s cautious optimism stems from a clinical trial, CARTITUDE-1, a 2018 study that ended in 2020 and looked at how well the CAR T-cell drug ciltacabtagene autoleucel (cilta-cel, brand name Carvykti) worked. In the trial, 97 patients received the drug. These patients “had gotten six prior lines of therapy, many had gotten a bone marrow transplant – sometimes two,” Banerjee says. Their prognosis was not good. But five years after the trial, a third of these patients were alive, free of disease, and no longer being treated for myeloma. The median survival rate for all who received the trial drug was a little more than five-and-a-half years. “When I meet newly diagnosed patients today, I still say myeloma is considered incurable, but now we’re actually having a discussion about what a cure would look like in myeloma,” says Banerjee, who is a member of the Working Group. It’s just a starting point, he cautions, “because we don’t know what the 15-year outcomes will be for that study.”
Working With Your Doctor to Treat Your Multiple Myeloma
Multiple myeloma is a complex disease, and the options to treat it are often changing. When considering treatment for his patients, Cho says he asks the following questions:
- Where are they in their myeloma journey? Is it early; is it late?
- Have they had many prior therapies or only a few?
- How capable are they of tolerating the side effects of certain treatments?
- Do they live near a hospital?
- Do they live with someone or have other caregivers?
- Do they have work or child care responsibilities?
“This is not just a cookie-cutter decision. You have to tailor the therapy options for the patient,” Cho says. “We have the good fortune now to have many good options for treatment, but they all have advantages, they all have risks. And that is a decision you need to make with a patient.”
Even if you live far from a hospital or center with advanced myeloma treatments, you could still benefit from adding a myeloma specialist to your treatment team, Banerjee says. “For over a third of my patients – actually half of my patients – I’m not their primary cancer doctor. Whether they live in Seattle or 2,000 miles away in rural Alaska, they have a primary oncologist who has boots on the ground and knows them best.” As close as a video call away, he’s there to help them navigate the changing landscape of myeloma treatment.
