Cilta-cel was linked with low progression events and a potential cure fraction in relapsed/refractory multiple myeloma.
Ciltacabtagene autoleucel (cilta-cel; Carvykti) yielded low rates of progression-free survival (PFS) events among patients with relapsed/refractory multiple myeloma with standard-risk cytogenetics, according to long-term follow-up data from the phase 3 CARTITUDE-4 trial (NCT04181827) presented at the
Findings showed that at a median follow-up of 33.6 months for the intention-to-treat population, patients with standard-risk cytogenetics treated with cilta-cel (n = 69) achieved a PFS rate of 71.0% compared with 43.2% for patients treated with standard-of-care (SOC) regimens (n = 70; HR, 0.43). Among patients with high-risk cytogenetics, the PFS rate was 52.3% for cilta-cel (n = 123) vs 17.5% for SOC (n = 132; HR, 0.38). For the standard-risk population, the OS rate was 79.7% for cilta-cel compared with 69.6% for SOC (HR, 0.62); in the high-risk population, the respective OS rates were 75.5% vs 62.1% (HR, 0.54).
Notably, patients with standard-risk cytogenetics treated with cilta-cel achieved an overall response rate (ORR) of 100%, including in patients without 1q gains or amplifications (n = 59) and those with 1q gains or amplifications (n = 105). The respective complete response (CR) or better rates for these populations were 90% and 92%. Comparatively, in the phase 1 CARTITUDE-1 trial (NCT03548207), which evaluated cilta-cel in a more heavily pretreated population compared with CARTITUDE-4, patients with standard-risk cytogenetics, including those with 1q gains or amplifications (n = 68), achieved an ORR of 94.1% and a CR or better rate of 82%.
“Earlier treatment with a single infusion of cilta-cel improved survival outcomes for patients with standard-risk disease, extending time free from treatment and progression,” lead study author Luciano Costa, MD, and colleagues wrote in a publication of the data. “The low rate of progression events in patients with relapsed/refractory multiple myeloma is indicative of a potential cure fraction.”
Costa is the Mary and Bill Battle Professor of Multiple Myeloma and director of the Multiple Myeloma Research and Treatment Program at the University of Alabama at Birmingham.
In April 2024,
This followed
CARTITUDE-4 included patients at least 18 years of age with multiple myeloma who were refractory to lenalidomide and had received 1 to 3 prior lines of therapy that including a PI and an IMiD.1 Patients also needed to have an ECOG performance status of 0 or 1. Those who received prior treatment with CAR T-cell therapy or a BCMA-targeting therapy were excluded.
Patients were randomly assigned 1:1 to received cilta-cel at a target dose of 0.75 x 106 CAR+ T cells/kg or SOC therapy with daratumumab (Darzalex) plus pomalidomide (Pomalyst) and dexamethasone (DPd) or pomalidomide plus bortezomib (Velcade) and dexamethasone (PVd). Those in the cilta-cel arm received at least 1 cycle of bridging therapy with PVd or DPd.
PFS served as the trial’s primary end point. Secondary end points included CR or better rate, ORR, minimal residual disease (MRD)–negativity rate, OS, and safety.
The analysis presented at the 2026 Transplantation & Cellular Therapy Meetings focused on outcomes for patients with standard-risk cytogenetics treated in CARTITUDE-4. It also included data from the standard-risk population treated in CARTITUDE-1.
Findings also showed that the 30-month PFS rates were 80.5% for patients with standard-risk cytogenetics and no 1q gain/amplification treated with cilta-cel in CARTITUDE-4; 71.7% for patients with standard-risk cytogenetics and 1q gain/amplification treated with cilta-cel in CARTITUDE-4; and 59.9% for patients with standard-risk cytogenetics treated with cilta-cel in CARTITUDE-1, irrespective of 1q gain/amplification status. The 30-month OS rates in these groups were 87.3%, 86.1%, and 70.6%, respectively. Notably, patients in the CARTITUDE-4 groups received a median of 2 prior lines of therapy, and those in the CARTITUDE-1 group received a median of 6 prior lines of therapy.
Additionally, among patients with standard-risk cytogenetics and no 1q gain/amplification treated with cilta-cel in CARTITUDE-4, 86% were progression-free and alive after 1 year. Among these patients, the 30-month PFS and OS rates were 93.1% and 93.7%, respectively. In MRD-evaluable patients (n = 32), the MRD-negative CR rate was 81%, and all 26 of patients to achieve an MRD-negative CR were progression-free at 30 months.
Regarding the safety of cilta-cel in the CARTITUDE-4 standard-risk population (n = 59), non-hematologic serious adverse effects (AEs) occurred in 52.5% of patients, and grade 3/4 infections were reported in 28.8% of patients. Other AEs included cytokine release syndrome (74.6%), immune effector cell–associated neurotoxicity syndrome (1.7%), and cranial nerve palsy (6.8%).
Secondary primary malignancies were reported in 13.6% of patients, including cutaneous/non-invasive malignancies (n = 4) and non-cutaneous/invasive malignancies (n = 4); no hematologic secondary malignancies were reported. The non-relapse mortality rate was 10.2% (n = 6). Four of these deaths were reported in the first year following treatment and included COVID-19 (n = 2), subdural hematoma (n = 1), and multiple organ dysfunction (n = 1). Two deaths occurred after 1 year, due to gastric adenocarcinoma (n = 1) and angiosarcoma (n = 1).
