A recent study indicates a significant correlation between real-world results and outcomes from clinical trials for a diverse group of patients suffering from relapsed or refractory multiple myeloma. This is the first study to report on real-world findings related to ciltacabtagene autoleucel (cilta-cel), a CAR-T cell therapy designed for multiple myeloma, revealing that patients encountered similar efficacy and safety results to those observed in clinical trials.
This first-ever study showcasing real-world outcomes from ciltacabtagene autoleucel (cilta-cel), a CAR-T therapy for multiple myeloma, highlights that patients experienced efficacy and safety results akin to those seen in clinical trials, as detailed in findings published today in Blood.
Among the 236 patients who received cilta-cel infusions across 16 medical centers in the U.S. during 2022, 89% experienced a positive response to the treatment, and 70% achieved a complete response, indicating no detectable cancer post-treatment. These figures are comparable to the phase II CARTITUDE-1 trial that supported cilta-cel’s approval by the U.S. Food and Drug Administration (FDA), which reported a 98% response rate and an 83% complete response rate.
Researchers found it particularly encouraging that over half of the participants in the new study would have been considered ineligible for the CARTITUDE-1 trial.
“In the real world, many patients have different performance statuses, organ functions, or baseline blood counts than those in the clinical trial that led to FDA approval [of this therapy]. Yet, these patients have demonstrated excellent outcomes,” shared Surbhi Sidana, MD, the lead author of the study and associate professor at Stanford University School of Medicine. “We observed commendable response rates that appeared to be lasting, even though more than half of the patients did not meet the eligibility criteria of the trial. The response rates and the time until progression or death reached the expected levels seen in clinical trials.”
Multiple myeloma is a type of cancer affecting plasma cells, which are a variety of white blood cells. Currently, approximately 40% of individuals diagnosed with this condition do not make it to the five-year mark after diagnosis, with the prognosis being significantly worse for patients who either fail to respond to standard treatments (refractory) or whose cancer recurs following an initial response (relapsed). Two CAR-T therapies have been authorized to treat these patients, where a patient’s immune cells are extracted, modified genetically, and reintroduced to combat cancer cells.
Cilta-cel received FDA approval in 2022 for patients whose multiple myeloma had either not been cleared or had relapsed after four or more lines of therapy; this approval was later broadened to include earlier treatment lines in April 2024. The current study concentrated on patients treated under the original approval for those with heavy prior treatments. For this investigation, researchers retrospectively reviewed outcomes of 255 patients who began the cilta-cel treatment process from March to December 2022. These patients had undergone a median of six prior therapies, with some having undergone as many as 18, without achieving a lasting response.
Out of the 255 patients who started receiving cilta-cel, 236 (around 92%) completed the entire treatment. Alongside the overall response rates, researchers looked into the outcomes of various subgroups, discovering that patients receiving the CAR T-cell product as per the FDA guidelines had better response rates (94% responded overall, and 76% achieved complete responses) compared to the one-fifth of patients whose CAR T cells did not meet the FDA’s quality requirements.
Additionally, researchers focused on a subgroup of patients who had previously undergone therapies targeting B cell maturation antigen (BCMA), a protein present on multiple myeloma cells. Given that cilta-cel targets BCMA, these patients were excluded from the CARTITUDE-1 trial. The study revealed that the 14% of participants falling into this category exhibited lower response rates compared to those who had not received BCMA-targeted therapies, with the differences being more significant in patients who had undergone such therapies recently. This insinuates that further investigation may assist in understanding how the timing of cilta-cel and other BCMA-targeted therapies could influence outcomes. The researchers also identified other essential patient and disease features linked to a lower probability of survival or a heightened likelihood of disease advancement.
Overall, serious side effect rates were similar to those reported in previous clinical trials. The study indicated that three-quarters of participants experienced cytokine release syndrome (CRS), a common and potentially severe side effect of CAR-T therapy, though only 5% faced grade 3 or higher complications. In total, 14% of participants noted neurotoxicity, and 10% reported delayed neurotoxicity; 2% experienced Parkinsonism.
Dr. Sidana noted, “Delayed neurotoxicity occurs more frequently with cilta-cel [in comparison to other CAR-T therapies], which is another factor we need to remain cognizant of.”
Furthermore, the study revealed a relatively high non-cancer-related mortality rate of 10%, primarily due to infections or CRS, indicating the potential for enhancements in infection management and CRS treatment.
Since this was a retrospective, real-world study, it did not feature a control group, and there might have been inconsistencies in outcome evaluation among the 16 centers that contributed data. Researchers suggested that subsequent studies could uncover ways to minimize serious side effects and explore whether earlier application of cilta-cel in cancer therapy could decrease toxicity risks.
