Although relapsed/refractory multiple myeloma (RRMM) has no cure yet, you can manage this chronic condition with the right treatment. Finding treatment that works for you can be tricky. Immune cells meant to help your body fight off infection start to work against you. Tumors can have different genetic and molecular structures that affect how they react to treatments. MM can also change over time and may stop responding to medicines you once took to slow its advance.
A one-size-fits-all treatment approach for RRMM doesn’t work. Instead, “it needs to be more tailored. We’re doing that already to some degree, but there’s still a lot to learn,” says Wael Harb, MD, a hematologist and medical oncologist at MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, CA.
Still, “there are really exciting new treatments available now and on the horizon,” says Christina Annunziata, MD, PhD, senior vice president of Extramural Discovery Science for the American Cancer Society.
Here are the latest RRMM treatments and a look at what else is on the way.
More Targets on Cancer Cells
CAR T-cell therapy helps your immune system find and destroy cancer cells.
“T cells are one of the immune cells that can directly kill cancer cells, but they need a target,” Annunziata says. “The CAR (chimeric antigen receptor) basically puts a receptor, or protein, on the surface of the T cell that allows it to recognize cancer cells.”
If you get CAR T-cell therapy, your doctor sends a sample of your T cells to a lab, where they’re changed so they can better see and fight cancer cells. Then the lab returns these custom-made fighter cells back to you.
So far, this path looks promising. After testing a newer type of CAR T-cell therapy called Ide-cel, researchers found it made cancer signs and symptoms go away for an average of 11 months.
The most common target of CAR T-cell therapy medicines is BCMA, a protein found on many multiple myeloma cells. At least six other targets are also in the works. In the future, BCMA-target medicines could be available to you earlier in your treatment. And once these medicines stop working, you still have plenty of other choices.
‘Off-the-Shelf’ Immune Cells
Over time, T cells “can become exhausted and lose the ability to fight,” Harb says. Another challenge doctors face is called “antigen escape,” which means cancer cells that escape killer T cells suddenly start growing.
“This is where there’s big research going on right now,” Harb says. “Can we engineer T cells so they don’t get exhausted and last longer? Can we engineer more than one protein so it prevents cells from escaping?”
Right now, CAR T-cell therapy relies on white blood cells that include T cells taken from your body. If your immune cells are too weak, the treatment might not work as well. Getting ready for CAR T-cell therapy is also a long process. A machine has to collect your blood, and new cells have to be created in a lab. You also need to have chemotherapy to stop your immune system from attacking the new T cells once you get them.
“The newer generation of cells will be ‘off-the-shelf,’ ” Harb says. “We’ll take them from a healthy person, not somebody with disease. That way, they can work for any person with myeloma. It will take away this complex procedure.”
In the future, these ready-to-use cells might also be improved to work better. “They may be able to last longer and prevent emergence of resistance,” Harb says.
Multitasking Antibodies
A monoclonal antibody is a special protein shaped like a “Y” that uses both “arms” to fight the same target – in this case, myeloma cells. Bispecific antibodies can use both arms to fight two targets. With one arm, these special antibodies latch onto a protein found on myeloma cells called GPRC5D. With the other arm, bispecific antibodies bind to a T cell. “They’re basically bringing the T cells next to the myeloma so the person’s own T cell can fight it,” Harb says.
This fall, the FDA approved a bispecific antibody called talquetamab-tgvs (Talvey) for people who’ve already tried four other types of RRMM treatment. You can get talquetamab-tgvs as a shot every week or every other week. According to one study, its effects can last at least 9 months.
Researchers are also testing bispecific antibodies that latch onto other proteins besides GPRC5D.
Vaccines
A vaccine against multiple myeloma may be an option in the not too distant future. “[It] would work by priming the body’s immune system to attack and kill the cancerous myeloma cells,” Annunziata says.
Vaccines can be made to work against specific proteins on the cell surface (like the BCMA protein that’s used in CAR T-cell therapy) or against a pool of proteins taken from myeloma cells. “These may be ‘personalized’ in that they’re extracted from a patient’s own myeloma cells, or they can be made from myeloma cell lines that are grown in the laboratory,” Annunziata says.
Vaccines for RRMM are in early clinical trials right now, so “the timing of FDA approval and availability to the general population would be several years if all goes well,” Annunziata says.
Stronger Medicines and Medicine Combinations
Even after finding new treatments for RRMM, doctors keep looking for ways to help these medicines work better. For instance, last year, the FDA approved a drug called isatuximab-irfc (Sarclisa) to treat RRMM. This monoclonal antibody can bind to CD38, a protein often found clustered on myeloma cells. Isatuximab-irfc then either flags the cancer cells so your immune system can destroy them or kills them all by itself.
This antibody can help people with RRMM who have already tried two or three other types of treatment. Studies show that isatuximab-irfc can work even better when combined with dexamethasone, a steroid that supports the immune system.
“When we see a good response, we start [asking questions like] ‘What if we give the same drug with this cocktail of drugs, or early on, or in a certain combination?’” Harb says. “We are always looking for new options, and we’re always trying to see if we can move an option to earlier lines of therapy so we don’t have to be concerned about relapse. We have made huge progress.”
Twenty-five years ago, someone with RRMM might have only lived a few years. “Now, there are many RRMM patients who are long-term survivors,” Harb says. “If we can help this person live a good quality of life and live many, many years without complications, that’s a big achievement.”
Show Sources
Photo Credit: (GIPhotoStock/Getty Images)
SOURCES:
Christina Annunziata, MD, PhD, senior vice president of Extramural Discovery Science, American Cancer Society.
Wael Harb, MD, hematologist and medical oncologist, MemorialCare Cancer Institute at Orange Coast Medical Center; vice president of medical affairs, Syneos Health.
American Cancer Society: “CAR T-cell Therapy and Its Side Effects.”
American Journal of Managed Care: “Discussing The Future of the RRMM Treatment Landscape.”
Blood: “Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.”
Cancer Research Institute: “Cancer Vaccines and Antigen Escape with CRI Lloyd J. Old STAR Dr. Joshua Brody.”
Drugs: “Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update.”
International Myeloma Foundation: “Sarclisa (isatuximab-irfc)”
Journal of Zhejiang University: “Current advances in chimeric antigen receptor T-cell therapy for refractory/relapsed multiple myeloma.”
National Cancer Institute: “FDA Approves BCMA-Targeted CAR T-Cell Therapy for Multiple Myeloma.”
News release, The Janssen Pharmaceutical Companies of Johnson & Johnson.
Targeted Oncology: “Isatuximab: A Review of Its Use in Multiple Myeloma.”
