In the first study to report real-world results of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR)-T therapy for multiple myeloma, patients experienced efficacy and safety outcomes similar to those seen in clinical trials, according to the results. published today in Blood.
Of 236 patients who received cilta-cel infusions at 16 US medical centers in 2022, 89% saw their cancer respond to treatment and 70% had a complete response, meaning there was no detectable cancer afterwards of the treatment. These figures are comparable to the results of the phase II CARTITUDE-1 trial that led to the approval of cilta-cel by the US Food and Drug Administration (FDA), which showed a response rate of 98 % and a complete response rate of 83%.
Most notable and encouraging, according to the researchers, was that more than half of the patients included in the new study would not have been eligible to participate in CARTITUDE-1.
“Although in the real world most 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, senior author of the study and associate professor at Stanford University School of Medicine. “We saw very high response rates that appeared to be durable, even though more than half of the patients did not comply [the trial’s] eligibility criteria. “Response rates and time to myeloma progression or death from any reason were within the range of outcomes seen in the clinical trial.”
Multiple myeloma is a cancer that affects 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 worse in patients who do not see their cancer eradicated with standard (refractory) treatments or who see their cancer return after an initial response ( relapse). Two CAR-T therapies have been approved for use in these patients, in which the patient’s own immune cells are removed, genetically altered, and then infused back into the body to attack and destroy cancer cells.
Cilta-cel was approved in 2022 for use in patients whose multiple myeloma had not been eradicated or had relapsed after four or more prior lines of therapy; approval was expanded to previous treatment lines in April 2024. The new study focused on patients who had received treatment according to the initial approval indication for heavily pretreated patients. For the new study, researchers retrospectively analyzed outcomes among 255 patients who began the process of receiving cilta-cel between March and December 2022. Study participants had undergone a median of six prior lines of therapy, and up to 18 lines of therapy. – without seeing a lasting answer.
Of the 255 patients who began the process of receiving cilta-cel, 236 (about 92%) underwent the full treatment. In addition to analyzing response rates for the entire study population, the researchers examined results among several subgroups. They found that patients who received the CAR T-cell product within the FDA-specified range had a higher response rate (94% saw an overall response and 76% saw a complete response) compared to one-fifth of patients who received the CAR T-cell product. The T cells did not fully meet the quality standards specified by the FDA.
The 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. Because cilta-cel targets BCMA, patients who had previously received such therapies were excluded from the CARTITUDE-1 trial. The researchers found that 14% of study participants who fell into this category showed 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 application 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 chance of survival or a higher chance 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 receiving cilta-cel infusions experienced cytokine release syndrome (CRS), a common side effect of CAR-T that can be serious, but only 5% experienced grade 3 events. 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 that we still have to take into account,” Dr. Sidana said.
The study also found a relatively high rate of non-cancer death (10%) among patients, primarily from infections or CRS, suggesting there may be room for improvement in decreasing infection risks and managing the condition. CSR.
As a real-world retrospective study, the study did not include a control group and there may have been discrepancies in outcome assessment and reporting among the 16 centers that contributed data. The researchers suggested that additional studies could help identify opportunities to reduce serious side effects and determine whether early use of cilta-cel during cancer treatment could help reduce the risk of toxicity.