The analysis shows patients achieved deep and durable responses despite being ineligible for the CARTITUDE-1 trial.
Standard-of-care (SOC) ciltacabtagene autoleucel (cilta-cel, Carvykti; Janssen Biotech Inc) demonstrated favorable efficacy and safety in patients with relapsed, refractory multiple myeloma (RRMM), according to a report of real-world. The data, published in Blood, found that patients treated with the chimeric antigen receptor (CAR) T-cell therapy achieved deep and durable responses, despite not meeting the CARTITUDE-1 trial (NCT03548207) eligibility.1,2
Cilta-cel is a CAR T-cell therapy that was originally approved by the FDA in 2022 for the treatment of adult patients with RRMM who have previously received 4 or more lines of therapy. In 2024, it received an additional indication for patients with RRMM who had at least 1 line of prior therapy. Cilta-cel is a BCMA-directed immunotherapy that targets overexpressed BCMA proteins on the surface of malignant myeloma cells. According to prior investigations, approximately 90% of patients with MM exhibit an overexpression of BCMA, which led to it becoming a significant therapeutic target for patients.3-5
Data from the CARTITUDE-1 trial, which led to cilta-cel’s initial approval, showed that about 98% of patients receiving the CAR T-cell product achieved an overall response rate (ORR) with a duration of response of 21.8 months. These results were extremely promising; however, the data was restricted to patients who were eligible for the trial. This led researchers across multiple United States institutions, including Stanford University and Moffitt Cancer Center and Research Institute, to examine the real-world outcomes of SOC cilta-cel in patients who were ineligible according to the eligibility requirements of the CARTITUDE-1 trial.1,3
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
Their study included data collected from 255 patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between March 1, 2022, and December 31, 2022, at 16 US academic medical centers. Of this population, 236 continued to cilta-cel therapy. According to the researchers, 54% of the participants would not have met the eligibility criteria for the CARTITUDE-1 trial, indicating the real-world patients were more diverse than the trial population.1
The participants were divided into 2 subgroups based on whether they received conforming cilta-cel (n= 191) or conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n=152). The end points included in the analysis were ORR, complete response (CR), and progression-free survival (PFS).1
According to the data, the 236 patients treated with cilta-cel achieved an 89% ORR and a CR of 70%. Of those who received conforming cilta-cel, there was a reported ORR of 94% and a CR of 74%. In the cilta-cel with fludarabine/cyclophosphamide lymphodepletion group, the researchers reported an ORR and CR of 95% and 76%, respectively.1
The median PFS was not reached at the time of analysis; however, the data showed that 68% of patients were progression-free at 12 months (95% confidence interval, 62-74). The researchers reported various independent risk factors that were associated with inferior PFS including high ferritin levels, high-risk cytogenetics, and extramedullary disease. Additionally, they note a potential trend indicating that prior BCMA therapy may affect PFS; however, this was not statistically significant.1
The most common adverse events (AEs) included cytokine release syndrome (75%), immune effector cell-associated neurotoxicity syndrome (14%; 4% grade ≥3 ICANS), and delayed neurotoxicity (10%).1
Non-relapse mortality occurred in 10% of patients, which were mostly a result of infection. The researchers also reported cases of secondary primary malignancies and myeloid malignancies/acute leukemia in 5.5% and 1.7% of patients, respectively. Considering these data, they recommend close surveillance to mitigate these AEs is crucial.1
The study highlights the consistency of cilta-cel’s effectiveness across different patient subgroups, suggesting the potential for broader application of cilta-cel in treatment of patients with RRMM in real-world SOC. This paves the way for opportunities to expand this efficacious CAR T-cell therapy to patients in need of alternative therapeutic options.
