Real-world data is affirming the efficacy of ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with relapsed or refractory multiple myeloma, while idecabtagene vicleucel (ide-cel; Abecma) is showing promise in treating patients with central nervous system (CNS) involvement of the disease. These findings, presented at recent medical conferences and published in journals, provide valuable insights into the use of these CAR T-cell therapies in broader patient populations and in challenging clinical scenarios.
Cilta-Cel Demonstrates Consistent Efficacy in Real-World Setting
A retrospective study of 236 patients who received cilta-cel infusions at 16 U.S. academic medical centers in 2022 demonstrated an 89% overall response rate and a 70% complete response (CR) rate. These results align favorably with the Phase II CARTITUDE-1 trial, which led to cilta-cel's FDA approval, showing a 98% response rate and an 83% CR rate. The real-world study included a significant proportion (56%) of patients who would have been ineligible for the CARTITUDE-1 trial due to factors such as poorer performance status, organ dysfunction, or lower baseline blood counts.
According to lead author Dr. Surbhi Sidana, Associate Professor at Stanford University School of Medicine, the study's findings suggest that cilta-cel can be effective even in patients who are less fit than those typically enrolled in clinical trials. The estimated 12-month progression-free survival (PFS) and overall survival (OS) in infused patients were 68% and 82%, respectively, which are within the range of results observed in the CARTITUDE-1 trial (77% and 89%, respectively).
However, the study also revealed a higher rate of non-relapse mortality (NRM) at 10%, compared to the 6% seen in CARTITUDE-1, potentially due to the higher proportion of patients with comorbidities and poorer performance status. Additionally, the study found that patients who received prior BCMA-targeted therapies had lower response rates to cilta-cel, particularly if the therapies were recent, suggesting that the timing of cilta-cel and other BCMA-targeted therapies may impact outcomes.
Ide-Cel Shows Favorable Outcomes in CNS Myeloma
In a separate real-world analysis, ide-cel demonstrated favorable responses in patients with relapsed/refractory multiple myeloma affecting the central nervous system (CNS). The multicenter retrospective study, conducted across seven tertiary care centers in Germany and Switzerland, included 10 patients with confirmed CNS myeloma. After a median follow-up of 4.7 months, 70% of patients had no CNS relapse after ide-cel treatment, with an estimated median progression-free survival (PFS) of 10.5 months and estimated median overall survival (OS) of 12.9 months.
The study also found that CAR T-cells were detectable in the cerebrospinal fluid (CSF) of patients after ide-cel treatment, indicating sufficient CNS penetration. While some patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS), none had severe (Grade 2 or higher) ICANS, and CRS was mostly Grade 2 or 3.
Renal Impairment Does Not Negatively Impact BCMA-Targeted CAR T-Cell Therapies
Another real-world analysis explored the impact of baseline renal impairment on the efficacy and safety of BCMA-targeting CAR T-cell therapies, including cilta-cel and ide-cel. The study found that patients with renal impairment had similar progression-free survival (PFS) and overall survival (OS) outcomes compared to those with normal renal function. However, patients with renal impairment experienced higher rates of ICANS and infections, suggesting that close monitoring may be warranted in this population.
