The real-world study results of ciltacabtagene autoleucel are comparable to data from the CARTITUDE-1 trial, emphasizing its efficacy and safety.
In the first real-world study, ciltacabtagene autoleucel (cilta-cel) (Carvykti; Janssen Biotech Inc), a chimeric antigen receptor (CAR) T-cell therapy, demonstrated significant efficacy and safety results in standard of care (SOC) for the treatment of patients with relapsed/refractory multiple myeloma (R/R MM), similar to those seen in clinical trials.
The development of CAR T-cell therapy has drastically changed the health outcomes of patients with R/R MM, offering therapeutic options with improved efficacy and decreased risk of toxicities. CAR T-cell therapy utilizes a patient’s own T-cells and equips them with artificially manufactured receptors that target specific proteins overexpressed on malignant cells. Cilta-cel is a BCMA-targeting CAR T-cell therapy approved by the FDA in 2022 for the treatment of adult patients with R/R MM who have received at least 4 or more prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. The decision was based on positive results from the CARTITUDE-1 trial (NCT03548207).1,2
In the SOC study, researchers evaluated 255 participants who underwent leukapheresis and 236 who received cilta-cel from March 1, 2022, to December 31, 2022, across 16 US medical centers. According to the data, 89% saw their cancer respond to the treatment and 70% had a complete response rate (CRR), which was similar to clinical trial results showing a 98% response rate and an 83% CRR. The researchers also found that patients who received the CAR T-cell product within the range specified by the FDA had a higher response rate, suggesting the benefit of further studies to determine how the timing of these treatments impact patient health outcomes.3,4
“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,” Surbhi Sidana, MD, the study’s lead author and associate professor at Stanford University School of Medicine, said in a press release. “We saw very high response rates that appeared to be durable, despite over half of the patients not meeting [the trial’s] eligibility criteria.”4
Trial Name: A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1)
ClinicalTrials.gov ID: NCT03548207
Sponsor: Janssen Research & Development LLC
Completion Date: August 2022
Instances of adverse effects were also similar to those observed in prior clinical trials, of which cytokine release syndrome (CRS) and neurotoxicity were the most common. In the SOC study, approximately 75% of patients receiving cilta-cel experienced CRS; however, only 5% experienced events of grade 3 or higher. Additionally, 14% of study participants experienced neurotoxicity, 10% experienced delayed neurotoxicity, and 2% experienced Parkinsonism. The researchers reported a relatively high mortality rate of 10% primarily resulting from infections and CRS.3,4
The real-world findings show great promise for the advancement of CAR T-cell therapy to patients with R/R MM who have progressed despite multiple lines of treatment. Further studies are needed to optimize cilta-cel and develop more efficacious methods of reducing risk of infection and more effectively managing CRS in patients with R/R MM.
