Ciltacabtagene autoleucel led to an overall response rate of nearly 98% in heavily pretreated patients with relapsed/refractory (R/R) multiple myeloma (MM), according to longer-term results from the CARTITUDE-1 phase Ib/II study.
Thomas Martin, MD, of the University of California, San Francisco, and colleagues, conducted the study and published its results in the Journal of Clinical Oncology.
The study included 97 patients with R/R MM who received at least three prior lines of therapy or were refractory to a proteasome inhibitor and immunomodulatory drug, and had received prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. The researchers previously reported “early, deep, and durable responses” to the treatment in these patients after 12 months.
At a median follow-up of 27.7 months, the overall response rate was 97.9% (95% CI, 92.7 to 99.7), with 82.5% (95% CI, 73.4 to 89.4) of patients achieving a stringent complete response. The median progression-free survival (PFS) and overall survival (OS) were not reached. The 27-month PFS rate was 54.9% (95% CI, 44.0 to 64.6) and the 27-month OS rate was 70.4% (95% CI, 60.1 to 78.6), respectively. The median duration of response was not estimable.
The overall response rates were 95.1% to 100% across subgroups, but duration of response, PFS and/or OS were shorter in patients with high-risk cytogenetics, International Staging System stage III disease, high tumor burden, or plasmacytomas.
Minimal residual disease (MRD) progress was evaluable in 61 patients, with 91.8% achieving MRD negativity at the 10−5 threshold. MRD negativity was sustained for at least six months in 68% of patients, and at least one year in 55% of patients. The PFS rate in patients who had sustained MRD negativity for at least six months was 73% and 78.8% in patients with sustained MRD negativity for at least a year.
The safety profile was “manageable” with no new treatment-related cytokine release syndrome and one new case of parkinsonism since the last report, the authors reported.
“Deep and durable responses to [ciltacabtagene autoleucel] are demonstrated at 28 months with a positive risk/benefit profile. Median progression-free survival and overall survival have not been reached,” Dr. Martin and colleagues wrote. “All high-risk patient subgroups had high response rates, suggesting that [[ciltacabtagene autoleucel] offers greater efficacy than what is observed with other available treatment options in these patients.”
Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up. J Clin Oncol. 2022. doi:10.1200/JCO.22.00842