Could CAR-T Therapy Treat  High-Risk Smoldering Myeloma? Latest Research Results from AACR

Smoldering multiple myeloma is a precursor condition of multiple myeloma. It is an earlier stage where the disease is present but does not yet cause symptoms. Patients with high-risk smoldering myeloma have a higher chance of progressing to active multiple myeloma. 

At the recent American Association for Cancer Research (AACR) Annual Meeting, researchers shared results from a study exploring whether CAR-T therapy could be used before symptoms of active myeloma develop.

Using CAR-T to treat smoldering myeloma is a big step to myeloma care.  Until recently, the only action after a smoldering myeloma diagnosis was a strategy called “watch and wait.” This is when you are carefully monitored to look for signs of active myeloma. In November 2025, the U.S. Food and Drug Administration (FDA) approved the drug combination daratumumab and hyaluronidase (Darazlex Fasapro) for high-risk smoldering myeloma. This research may point to another possible treatment option.  

The CAR-PRISM study: CAR-T for smoldering myeloma

The CAR-PRISM trial evaluated a type of CAR-T therapy called ciltacabtagene autoleucel (Carvykti), also known as cilta-cel, in 20 patients with high-risk smoldering myeloma. They received a single infusion of the therapy without any prior induction.  

The results showed that 100% of patients achieved a complete response, and every single patient reached MRD-negative status (no detectable disease) within two months. This deep response has remained stable and participants remained disease free after 18 months. 

While side effects like low blood counts and mild immune reactions were common, they didn’t last for many days. Researchers also identified specific immune patterns that help them use lower doses and steroids to make the treatment safer. 

These findings suggest that early use of CAR-T therapy can provide rapid and lasting results for high-risk patients before the disease becomes active.

What were common side effects after CAR-T?

The side effects were consistent with known CAR-T risks, though researchers are using these results to improve safety strategies. 

• Low blood counts (neutropenia): This was common but lasted about three days.
• Cytokine Release Syndrome (CRS): This occurred in all patients, but all cases were mild to moderate.
• Neurologic side effects: Some patients experienced tremors or tingling. Two patients had more complex neurologic symptoms.

This investigation is ongoing to ensure patient safety. Researchers will test adjustments such as lower CAR-T dosing and the earlier use of steroids like dexamethasone to manage the immune response.

Using CAR-T for a precursor condition is groundbreaking in the cancer care field

This is the first study to test CAR-T therapy in a precursor condition. The early results suggest that treating high-risk smoldering myeloma earlier may be more beneficial in the long term than waiting until active disease. However, because this was a small, single-center study, larger trials are required to confirm if this will change the standard of care or lead to a functional cure.

Staying informed about groundbreaking treatment options can help people with high-risk smoldering myeloma stay hopeful for better outcomes, and delaying progression to active myeloma. 

Create a your free HealthTree account to track your M-spike and light chain levels. By securely connecting your records, you can monitor your risk of progression and prepare for detailed discussions with your doctor about early intervention options. 

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Source: CT103 - Ciltacabtagene autoleucel in high-risk smoldering myeloma: Results from the CAR-PRISM trial