Could a treatment developed for multiple myeloma change care for AL amyloidosis?

CAR-T cell therapy has changed how doctors treat some blood cancers, including multiple myeloma. Now, researchers are wondering if this same approach might help people with AL amyloidosis, a rare blood disease caused by abnormal plasma cells. 

What is AL amyloidosis?

AL amyloidosis, also called light-chain amyloidosis, begins in plasma cells, which are a type of immune cell found in your bone marrow. Normally, plasma cells make antibodies that fight infections. But, in AL amyloidosis, some abnormal plasma cells make faulty pieces of antibodies called light chains. These abnormal light chains clump together and form deposits called amyloid in tissues and organs throughout the body. Over time, these deposits can stop affected organs from working properly. The heart and kidneys are most often affected, although the disease can involve other parts of the body as well.

Treating AL amyloidosis means stopping the abnormal plasma cells from producing the light chains that cause damage. This is where the disease overlaps with multiple myeloma; although they are different conditions, both involve abnormal plasma cells, so some myeloma therapies are also used to treat AL amyloidosis. 

But, people with AL amyloidosis, especially when the heart is affected, can have poorer outcomes than people with multiple myeloma because their organs are already damaged by the time they are diagnosed. They are also generally more fragile, which makes it harder to tolerate the strong treatments used for multiple myeloma. 

Treatment options have also historically been limited.  Until 2021, no drug had ever been approved specifically for AL amyloidosis. That year, a treatment regimen containing daratumumab (Darzalex Faspro) became the first FDA-approved treatment specifically for AL amyloidosis. For patients whose disease does not respond well to initial treatment, or whose disease returns, there are still no approved options. That gap is what researchers hope CAR-T cell therapy might fill.

What is CAR-T cell therapy?

CAR-T cell therapy is a type of immunotherapy that uses a patient’s own immune cells to recognize and attack specific cells.

The process begins by collecting T cells from the patient’s blood. T cells are a type of white blood cell that helps the immune system fight disease. Then, in a lab, scientists change these T cells so they produce something called a chimeric antigen receptor, or CAR. This CAR acts like a marker that helps the T cells recognize a particular target on the surface of other cells.

The modified CAR-T cells are then infused back into the patient, where they look for cells carrying that target and eliminate them.

CAR-T therapies have already become an important treatment for certain blood cancers, including multiple myeloma, for which there are two FDA-approved cell therapies.

Why use CAR-T for AL amyloidosis?

The link goes back to the abnormal plasma cells that cause AL amyloidosis.

CAR-T therapies for multiple myeloma are designed to recognize targets found on plasma cells. The CAR-T cells then attack the abnormal plasma cells in the bone marrow, which can lead to long-lasting remission.

Researchers are now exploring whether the same strategy can work in AL amyloidosis. The goal is to target the abnormal plasma cells so they stop producing harmful light chains. Without those proteins circulating in the body, amyloid can no longer build up in organs and cause damage. 

Early studies of CAR-T cell therapy in AL amyloidosis showed promising results, leading to a follow-up clinical trial called NEXICART-2. The research underway now will help determine what role this approach could play in treating the disease.

What makes the MCC trial significant?

The Masonic Cancer Center is the only site in Minnesota participating in NEXICART-2, the first U.S. clinical trial studying this CAR-T cell therapy in people with relapsed or refractory AL amyloidosis. Results like this prove that there are many applications for the types of treatments that our cancer researchers study—and they're not just limited to one disease. 

Early results from the trial have been encouraging, including responses among patients with advanced disease and significant organ dysfunction. Researchers have also seen a manageable side-effect profile. Most patients experienced Grade 1 cytokine release syndrome, an inflammatory reaction that can occur after CAR-T cell therapy, which typically appeared as a fever and resolved quickly.

Researchers are particularly interested in the potential for CAR-T cell therapy to provide a lasting response after a single infusion.  Unlike treatments that require ongoing therapy, CAR-T cells are given once and are designed to remain active in the body. If this approach proves effective over time, it could reduce the amount of treatment patients need while providing durable control of the disease.

Looking ahead: Could CAR-T be used earlier?

NEXICART-2 is studying CAR-T cell therapy in people with relapsed or refractory AL amyloidosis, meaning their disease has returned or has not responded to previous treatment. Researchers are now preparing to study whether CAR-T could also benefit people earlier in their disease.

The planned NEXICART-3 trial will study CAR-T cell therapy as a frontline treatment for people who are newly diagnosed with AL amyloidosis. Researchers hope to learn whether using CAR-T earlier can produce a rapid and lasting response while limiting the amount of ongoing treatment patients need.

Ultimately, the study could help determine whether those early responses translate into better long-term outcomes for people with AL amyloidosis.