Cilta-cel CAR T-cell Therapy: Unprecedented Long-Term Outcomes in Relapsed and Refractory Myeloma

New data from two long-term studies show unprecedented outcomes for people with relapsed and refractory multiple myeloma treated with a CAR T-cell therapy called ciltacabtagene autoleucel, also known as cilta-cel (Carvykti, Johnson & Johnson).

For people living with relapsed or refractory myeloma, CAR T-cell therapies like cilta-cel are a promising treatment option. Cilta-cel was approved by the U.S. Federal Drug Administration (FDA) in 2022 for relapsed or refractory myeloma that had been previously treated with 1 or more other therapies. Now, new results from the CARTITUDE-1 and CARTITUDE-4 clinical trials have shown unprecedented long-term results for people with myeloma treated with cilta-cel. The research was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and featured in The New York Times this June.  

About the CARTITUDE-1 and CARTITUDE-4 clinical trials

CARTITUDE-1 was the first clinical trial designed to test how well cilta-cel controls relapsed or refractory myeloma to help people live longer. The study participants had previously received 3 or more treatments or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD). These patients had received treatment with a PI, IMiD, and anti-CD38 therapy. Typically, people in this group have a median progression-free survival (PFS) of less than 6 months and a median overall survival (OS) of about 1 year. 

CARTITUDE-1 was a phase I/IIb single-arm clinical trial where all 97 patients received a single cilta-cel infusion. These patients have now been followed for 5 years. 

The phase 3 CARTITUDE-4 study tested cilta-cel in patients who had received 1 to 3 prior lines of therapy. The study compared cilta-cel to the standard of care drug combinations used in everyday practice (such as PVd and DPd). CARTITUDE-4 followed patients for 3 years.

Encouraging overall survival rates

Both studies showed encouraging OS rates, which is a measure of how long people live after starting therapy. For patients in CARTITUDE-1, the median OS was just over 5 years (60.6 months). 

In the CARTITUDE-4 trial, the median OS had not yet been reached in the cilta-cel treatment group after 3 years. This means that more than half of the people treated with cilta-cel were still alive at the time of the study analysis. In comparison, people receiving standard of care treatments had a median OS of less than 3 years (34 months). 

Among those who received cilta-cel earlier, 50% had no signs of cancer 1 year after treatment, compared to 10% who had received the standard of care.

Longer progression-free survival for many

Progression-free survival (PFS) measures how long a person lives after starting treatment without the myeloma worsening. 

In the CARTITUDE-1 trial, 32 out of 97 patients (33%) remained alive with no signs of cancer progression for 5 years or longer. These patients did not need any additional myeloma treatment during that time.

Among those who stayed progression-free for 5 years or longer:

• The median age was 60. 
• They had received a median of 6.5 prior treatments. 
• 23.3% had high-risk genetic features.
• 12.5% had extramedullary disease, which is when myeloma spreads outside the bone marrow. 
• 90.6% were triple-class refractory, which means they were resistant to an IMiD, a PI, an IMiD, and an anti-CD38 antibody.
• 46.9% were penta-drug refractory, which means they were resistant to at least 2 IMiDs, 2 PIs, and 1 anti-CD38 antibody. 

In CARTITUDE-4, the median PFS had not yet been reached for patients treated with cilta-cel who had received 1, 2, or 3 prior lines of treatment. For those who received standard of care treatments, the median PFS varied depending on how many prior treatments they had received. 

• After 1 prior line of treatment, patients receiving standard of care had a median PFS of 17 months. 
• After 2 prior lines of treatment, they had a median PFS of 12 months. 
• After 3 prior lines of treatment, they had a median PFS of 8 months. 

The study also showed that in patients with extramedullary disease, those who received cilta-cel had a median PFS of 13 months, compared to 4 months with standard treatment. 

For people living with difficult-to-treat myeloma, longer PFS shows that the therapy is effectively controlling the cancer.

Lasting results with minimal residual disease negativity

Minimal residual disease negativity (MRD negativity) means that no detectable myeloma cells remain after treatment and is often linked to longer PFS and OS. In CARTITUDE-1, there was one group of 12 people followed for 5 years at a single center. All 12 remained MRD-negative with no cancer visible on PET/CT scans. This shows that lasting responses with cilta-cel are possible even several years after treatment.  

Read more about MRD negativity and survival at the link below. 

What Does It Mean To Be MRD Positive or Negative? 

What this means for people with myeloma

The results of the CARTITUDE-1 and CARTITUDE-4 clinical trials confirm that cilta-cel CAR T-cell therapy provides lasting results for some people living with relapsed and refractory myeloma, even after many previous treatments. “We are moving the needle from an incurable disease in multiple myeloma to a potentially curable disease,” said Sundar Jagannath, MBBS, a Professor of Medicine at Icahn School of Medicine at Mount Sinai in New York.   

Real-world data continues to be important for understanding how therapies like cilta-cel perform outside of clinical trials. You can contribute by completing surveys through HealthTree Cure Hub®, which helps improve outcomes for people with myeloma.

HealthTree Cure Hub

Click below to watch a HealthTree University video overview of the latest cilta-cel results from Dr. Sundar Jagannath, MBBS, Mount Sinai

Sources: 

• CARTITUDE-1 
• CARTITUDE-4 
• HealthTree University:  Could CAR-T Cure Myeloma?  
• New York Times: From No Hope to a Potential Cure for Deadly Blood Cancer