Idecabtagene vicleucel (ide-cel; Abecma) and ciltacabtagene autoleucel (cilta-cel; Carvykti), two CAR-T cell therapies, are showing promise in the treatment of multiple myeloma. Recent data from clinical trials highlight their potential to achieve high rates of complete response (CR) and minimal residual disease (MRD) negativity, leading to improved outcomes for patients. These findings were presented at the 2025 Transplant and Cellular Therapy Meetings and the 2024 American Society of Hematology (ASH) Annual Meeting.
Idecabtagene Vicleucel (Ide-Cel) in Post-Transplant Setting
Topline findings from the phase 2 BMT CTN 1902 trial (NCT05032820) demonstrated that ide-cel led to high CR rates and MRD negativity in patients with multiple myeloma who experienced a suboptimal response to standard first-line therapy, including autologous hematopoietic cell transplant (auto-HCT) and lenalidomide maintenance.
Alfred L. Garfall, MD, director of Autologous Hematopoietic Stem Cell Transplantation at the Hospital of the University of Pennsylvania, presented the data, noting that 63% of evaluable patients (n = 38) had converted to CR by 6 months. Time-to-event analysis indicated early responses, with potential for further improvements as data matures. At 6 months, 87% of patients achieved MRD negativity, with 95% reaching this status at some point during that period. After a median follow-up of 10.7 months, only one patient experienced disease progression.
Garfall concluded, "Anti-BCMA CAR T-cell therapy in this post-transplant setting is feasible and safe... Ide-cel used in the upfront setting after an autologous transplant was successful to upgrade the response, with most patients achieving an MRD-negative response and 63% achieving a CR by 6 months."
The single-arm, phase 2 study enrolled patients with multiple myeloma who had a suboptimal response (less than CR) following auto-HSCT and 3 months of lenalidomide-based maintenance. The primary endpoint was CR by 6 months. Secondary endpoints included overall responses, MRD negativity within 6 months, disease progression, lenalidomide initiation, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infections, and CAR T-cell in vivo expansion.
Ciltacabtagene Autoleucel (Cilta-Cel) Demonstrates Superior MRD Negativity
Updated data from the phase 3 CARTITUDE-4 trial (NCT04181827) revealed that ciltacabtagene autoleucel (cilta-cel) significantly increased MRD negativity rates compared with standard of care (SOC) in patients with lenalidomide-refractory multiple myeloma after 1 to 3 prior therapies.
The data, shared at the 2025 Transplant and Cellular Therapy Meetings, showed that among patients in the intention-to-treat population who received cilta-cel (n = 208), the MRD negativity rate at the 10-5 threshold was 62.0% vs 18.5% with SOC (n = 211; OR, 7.6; P < .0001). In MRD-evaluable patients, the MRD negativity rate at the same threshold with cilta-cel (n = 145) was 89.0% vs 37.9% with SOC (n = 103; OR, 13.3; P < .0001).
Yi Lin, MD, PhD, of Mayo Clinic, presented the data, stating, "With this longer follow-up on the CARTITUDE-4 study, not only are we seeing that benefit [in terms of] progression-free survival [PFS], but we’re seeing some of the deeper response in that single-dose treatment [with cilta-cel] without maintenance can achieve that higher level of MRD negativity of up to 10-6, many patients can sustain that for at least 1 year or longer, and that is translating into a corresponding much higher 30-month overall survival [OS] and PFS rates."
The CARTITUDE-4 trial enrolled patients with multiple myeloma who had received 1 to 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, and were refractory to lenalidomide. Patients were randomized 1:1 to receive cilta-cel or SOC treatment. The primary endpoint was PFS, with secondary endpoints including safety, OS, MRD negativity rate, and overall response rate.
Implications for Multiple Myeloma Treatment
These findings underscore the potential of CAR-T cell therapies like ide-cel and cilta-cel to achieve deep and durable responses in multiple myeloma patients. The high rates of MRD negativity observed with these therapies suggest that they may offer a significant improvement over standard treatments, particularly in patients with relapsed or refractory disease. Further research is needed to fully understand the long-term benefits of these therapies and to identify the patients who are most likely to benefit from them.
