Clinical Trials Versus the Real World: Evaluating Brexu-Cel in Relapsed/Refractory Mantle Cell Lymphoma

Take-aways:

• In this real-world analysis of patients with relapsed/refractory mantle cell lymphoma, the median time from CAR T-cell order and administration was 56 days and 87.2% of patients underwent bridging therapy.
• At 6 months following brexu-cel infusion, the progression-free survival rate was 57.9%, and median duration was 5.3 months.
• Cytokine release syndrome was reported in 78.7% of patients, with neurotoxicity observed in 48.9%.

A recent study of brexucabtagene autoleucel (brexu-cel; formerly known as KTE-X19) supports the use of the 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 1 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 brexu-cel 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 brexu-cel.

Beginning on January 7, 2020, a total of 57 patients were enrolled in the study. In 2 cases, patients decided not to move forward with treatment, so brexu-cel 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 brexu-cel, 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 3 prior lines of treatment (range, 2-8), and approximately one-third (34%) had 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 1 efficacy evaluation was 88%. This included complete responses (CR) for 61.9% of patients. At 6 months following brexu-cel 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 brexu-cel, 5 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.

Disclosures: This research was supported by Kite Pharma, a Gilead Company. Study authors report financial relationships with Gilead and Kite Pharma, the manufacturer of brexu-cel.

Reference

Herbaux C, Bret C, Di Blasi R, et al. Kte-X19 in relapsed or refractory mantle-cell lymphoma, a “real-life” study from the DESCAR-T Registry and Lysa Group. Abstract #743. Presented at the 2021 American Society of Hematology Annual Meeting, December 13, 2021.