Of 236 patients who received cilta-cel infusions at 16 U.S. medical centers in 2022, 89% saw their cancer respond to the treatment and 70% had a complete response, meaning there was no detectable cancer after the treatment. These numbers are comparable to the results of the phase II CARTITUDE-1 trial that led to cilta-cel’s approval by the U.S. Food and Drug Administration (FDA), which showed a 98% response rate and an 83% complete response rate.

Most notable and encouraging, according to researchers, was that over half of the patients included in the new study would have been ineligible to participate in CARTITUDE-1.

“Even though in the real world a majority of patients are not as fit in terms of performance status, organ function, or baseline blood counts as they were in the clinical trial that led to FDA approval [of this therapy], these patients can do very well,” said Surbhi Sidana, MD, the study’s lead author and associate professor at Stanford University School of Medicine. “We saw very high response rates that appeared to be durable, despite over half of the patients not meeting [the trial’s] eligibility criteria. The response rates and time until progression of myeloma or death due to any reason was within the range of results observed in the clinical trial.”

Multiple myeloma is a cancer affecting plasma cells, a type of white blood cell. Currently about 40% of people diagnosed with multiple myeloma do not survive five years, and the prognosis is poorest in patients who do not see their cancer eradicated with standard treatments (refractory) or who see their cancer return after an initial response (relapsed). Two CAR-T therapies, where a patient’s own immune cells are removed, genetically altered, and then infused back into the body to attack and kill cancer cells, have been approved for use in these patients.

Cilta-cel was approved in 2022 for use in patients whose multiple myeloma had not been eradicated or had relapsed after four or more previous lines of therapy; the approval was expanded to earlier lines of treatment in April 2024. The new study focused on patients who had received treatment under the initial approval indication for heavily pre-treated patients. For the new study, researchers retrospectively analyzed outcomes among 255 patients who began the process of receiving cilta-cel in March through December of 2022. The study participants had undergone a median of six prior lines of therapy — and up to 18 lines of therapy — without seeing a lasting response.

Of the 255 patients who started the process of receiving cilta-cel, 236 (about 92%) underwent the full treatment. In addition to analyzing response rates of the whole study population, researchers examined outcomes among several subgroups. They found that patients who received the CAR T-cell product within the range specified by the FDA had a higher response rate (with 94% seeing a response overall and 76% seeing a complete response) compared with the one-fifth of patients whose CAR T cells did not fully conform to the quality standards specified by the FDA.

Researchers also examined a subgroup that included patients who had received prior therapies targeting B cell maturation antigen (BCMA), a protein found on multiple myeloma cells. Since cilta-cel targets BCMA, patients who had previously received such therapies were excluded from the CARTITUDE-1 trial. Researchers found that the 14% of study participants who fell into this category did show lower response rates than those who had not previously received BCMA targeted therapies, with the difference being most pronounced in patients who had received BCMA targeted therapies more recently. This suggests that further studies could help elucidate how the timing of cilta-cel and other BCMA targeted therapies may affect outcomes. The researchers also identified other key patient and disease characteristics that were associated with a lower likelihood of survival or a higher likelihood of disease progression.

Overall, rates of serious side effects were similar to those reported in previous clinical trials. The study found that three-quarters of those who received cilta-cel infusions experienced cytokine release syndrome (CRS), a common CAR-T side effect that can be severe, but only 5% experienced events of grade 3 or higher. Overall, 14% of study participants experienced neurotoxicity and 10% experienced delayed neurotoxicity; 2% experienced Parkinsonism.

“Delayed neurotoxicity is predominantly seen with cilta-cel [compared with other CAR-T therapies], and that’s another trade-off we should still be aware of,” said Dr. Sidana.

The study also found a relatively high rate of death (10%) unrelated to patients’ cancer, mostly from infections or CRS, suggesting that there may be room for improvement in decreasing infection risks and managing CRS.

As a retrospective, real-world study, the study did not include a control group and there may have been discrepancies in outcomes assessment and reporting among the 16 centers that contributed data. Researchers suggested that additional studies could help to identify opportunities to reduce serious side effects and determine whether using cilta-cel earlier during cancer treatment could help to lower the risk of toxicity.