A recent study of KTE-X19 (also known as brexucabtagene autoleucel) supports the use of chimeric antigen receptor (CAR) T-cell therapy for the treatment of patients with relapsed or refractory mantle cell lymphoma (MCL) whose disease did not respond to at least one line of chemoimmunotherapy and a Bruton tyrosine kinase (BTK) inhibitor. Charles Herbaux, MD, of Montpellier University Hospital in France, presented data from the first analysis of “real-life” application of KTE-X19 at the 2021 American Society of Hematology Annual Meeting.
All patients with relapsed or refractory MCL who were registered in DESCAR-T, the French national registry for all patients with hematologic malignancies treated with CAR T cells, were eligible for the study. Investigators began collecting data at the time of the medical decision to treat with KTE-X19.
Beginning on January 7, 2020, a total of 57 patients were enrolled in the study. In two cases, patients decided not to move forward with treatment, so KTE-X19 was not ordered. Eight patients were ultimately not infused with CAR T cells because of disease progression (n = 3), manufacturing failure (n = 3), cardiovascular disease (n = 1), and uncontrolled infection (n = 1).
Among the 47 patients who were infused with KTE-X19, the median age at the time of registration with DESCAR-T was 67 years (range = 45-79). The majority of patients (93.6%) were male. Patients had received a median of three prior lines of treatment (range = 2-8), with 34% having previously undergone autologous stem cell transplant. At the time of enrollment, Ki67 was high (>30%) in 78.6% of patients, Lactate dehydrogenase levels were elevated in 52.4% of patients, and 21.1% of patients had a performance status of ≥2.
The median time from CAR T-cell order and administration was 56 days (range = 35-134), during which 87.2% of patients underwent bridging therapy. After CAR T-cell infusion, median follow-up was 3.3 months (range = 0-12.6). Investigators used Lugano criteria to assess responses. Best overall response rate for the 42 patients who had at least one efficacy evaluation was 88%. This included complete responses (CR) for 61.9% of patients. At six months following KTE-X19 infusion, the progression-free survival rate was 57.9%, and median duration was 5.3 months.
Cytokine release syndrome (CRS) was reported in 78.7% of patients, with neurotoxicity observed in 48.9%. Four patients (8.5%) experienced grade 3 or higher CRS or neurotoxicity. Intensive care unit transfer was required for 27.7% of patients, who were hospitalized for a median of five days. Among the 47 patients who were infused with KTE-X19, five deaths occurred. Four patients died of progressive disease and one of grade 5 CRS. “The safety profile and the overall response rate are in line with previously published data,” the authors wrote.