New research presented at the AACR Annual Meeting 2026 offers hope for people with high-risk smoldering multiple myeloma (SMM), which is a condition that can develop into active multiple myeloma.
In a small phase II clinical trial called CAR-PRISM, researchers found that a single infusion of the CAR T-cell therapy ciltacabtagene autoleucel (Carvykti) led to minimal residual disease (MRD)-negative status in every patient treated. Even more encouraging, none of the patients progressed to active multiple myeloma during the study’s follow-up period.
These early findings suggest that treating smoldering myeloma before symptoms begin may one day change the course of the disease.
What is smoldering multiple myeloma?
Smoldering multiple myeloma (SMM) is an early, asymptomatic form of myeloma. People with SMM do not yet have symptoms, but abnormal plasma cells are building up in the bone marrow.
Some patients have high-risk SMM, meaning the disease is more likely to become active multiple myeloma within a short time. Nearly half of patients with high-risk SMM develop active multiple myeloma within two years, often leading to complications such as:
- Bone damage
- Kidney problems
- Anemia
- Pain
- Frailty
Until recently, most people with SMM were closely monitored but did not begin treatment until symptoms appeared.
A new approach: Treating myeloma earlier
In late 2025, the U.S. Food and Drug Administration approved daratumumab hyaluronidase-fihj (Darzalex Faspro), the first treatment for high-risk SMM. It reduced the risk of progression by about 51%, but it requires regular treatment for up to three years.
Researchers wanted to know whether CAR T-cell therapy, which is already approved for people with relapsed multiple myeloma, could be used earlier.
CAR T-cell therapy works by collecting a patient’s T cells, engineering them to recognize cancer cells, and then infusing them back into the body to attack the disease.
The CAR T-cell therapy used in this study targets a protein called BCMA, which is found on abnormal plasma cells.
Researchers believed this approach might work especially well in smoldering myeloma because the immune system is still stronger at this earlier stage.
What the study found
The CAR-PRISM trial enrolled 20 patients with high-risk smoldering multiple myeloma.
After receiving one infusion of ciltacabtagene autoleuceli, the results were remarkable:
- 100% of patients became MRD-negative within two months
- No patients progressed to active multiple myeloma
- No deaths were reported during follow-up
- Responses were ongoing at a median follow-up of 15.3 months
MRD-negative means that even with very sensitive testing, doctors could not detect any remaining myeloma cells. This is considered a very deep response and is often linked to better long-term outcomes.
For patients and families, this raises the possibility that early treatment may not just delay myeloma—it may potentially stop it from becoming active.
What about side effects?
As with any CAR T-cell therapy, there were side effects, but they were generally manageable.
All patients experienced low-grade cytokine release syndrome (CRS), an immune reaction that can cause fever and flu-like symptoms. Importantly:
- No patients had severe CRS
- Some patients had temporary low blood counts, including neutropenia
- Seven patients had neurologic side effects, such as facial weakness or mild motor symptoms
In several cases, these nerve-related side effects improved or resolved completely.
While these risks are important to consider, the side effects seen in this trial were manageable and no unexpected safety concerns emerged.
Why this matters
This study suggests that using CAR T-cell therapy earlier, before multiple myeloma becomes active, may produce deeper responses than waiting until the disease progresses.
That could be a major shift in how high-risk smoldering myeloma is treated.
This research raises an important possibility: could early immunotherapy actually cure some patients before active multiple myeloma ever develops?
Important questions remain
Although these findings are encouraging, this was a small early-stage study with some important limitations:
- Only 20 patients were treated
- The study took place at one cancer center
- Follow-up has been relatively short
- Patients with more advanced smoldering disease were excluded
Larger studies with longer follow-up are needed before this approach becomes widely available.
Still, the results provide an exciting glimpse at a future where high-risk smoldering multiple myeloma may be treated proactively, before symptoms or organ damage occur.
For patients living with high-risk SMM, this could represent an important step toward preventing progression and possibly achieving long-term remission with just one treatment.
Get expert insights on the latest updates in multiple myeloma and watch our full webinar discussion with Dr. Saad Z. Usmani.
