Kite, a Gilead Company, has announced new data from multiple analyses of Tecartus (brexucabtagene autoleucel) at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, reinforcing its durable efficacy in patients with relapsed/refractory mantle cell lymphoma (R/R MCL) and relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). These findings highlight Tecartus as a significant treatment option, particularly for patients with limited alternatives.
ZUMA-2 Cohort 3: BTKi-Naïve Patients with R/R MCL
The primary analysis of ZUMA-2 cohort 3 (Abstract #748) evaluated Tecartus in 86 patients with R/R MCL who had not previously received a Bruton tyrosine kinase inhibitor (BTKi). The study met its primary endpoint, demonstrating an overall response rate (ORR) of 91% (95% CI, 82.5-95.9; P<.0001). A complete response (CR) was achieved in 73% of patients (95% CI, 62.6-82.2). With a median follow-up of 15.5 months (range, 1.4-27.1), the 12-month duration of response (DOR), progression-free survival (PFS), and overall survival (OS) rates were 80% (69.1-87.9), 75% (64.5-83.4), and 90% (80.7-94.4), respectively.
Dr. Tom van Meerten, lead investigator from University Medical Center Groningen, Netherlands, noted, "The high overall response rate, complete responses, and durable benefit demonstrated in ZUMA-2 cohort 3 indicate that brexu-cel can be used earlier in the treatment of relapsed/refractory mantle cell lymphoma."
The safety profile was consistent with previous findings, with a low rate of Grade ≥ 3 cytokine release syndrome (CRS) occurring in 6% of patients and Grade ≥ 3 neurological events (ICANS) in 21% of patients.
Five-Year Outcomes in R/R MCL (ZUMA-2 Cohorts 1 and 2)
Long-term follow-up data from ZUMA-2 cohorts 1 and 2 (Abstract #4388) showed that 39% of patients with R/R MCL were still alive after five years. In cohort 1, median follow-up was 67.8 months, with median DOR and PFS of 36.5 months and 25.3 months, respectively. The 60-month OS rate was 39%. Cohort 2, which assessed a lower dose of Tecartus, showed a 54% OS rate at 60 months. No new safety signals or secondary T-cell malignancies were reported.
Dr. Michael Wang, lead investigator from The University of Texas MD Anderson Cancer Center, stated, "More than three years after its approval, brexu-cel continues to deliver in relapsed/refractory mantle cell lymphoma... It is encouraging to see these results in a heavily pre-treated population and consistency across both cohorts."
Real-World Evidence in R/R B-ALL
Real-world outcomes in adults with R/R B-ALL treated with Tecartus (Abstract #5092 and #4193) were analyzed using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry. The analysis included 242 evaluable patients and demonstrated a CR/CRi (complete remission with incomplete hematologic recovery) rate of 80% after Tecartus treatment. The estimated six-month rates of DOR and OS were 67% and 80%, respectively.
Dr. Kitsada Wudhikarn, lead investigator from Chulalongkorn University, Bangkok, Thailand, commented, "In this real-world analysis of brexu-cel, we see an efficacy and safety profile consistent with the findings of the pivotal ZUMA-3 study in relapsed/refractory B-cell acute lymphoblastic leukemia, but in a broader patient population."
The rates of any grade CRS and ICANS by 100 days were 81% and 46%, respectively. These findings support the utility of Tecartus in treating this aggressive hematologic malignancy.
Impact of Disease Burden and CAR-T Expansion in ZUMA-3
An additional analysis (Abstract #4193) evaluated clinical and pharmacokinetic/pharmacodynamic data from the ZUMA-3 study. Results indicated that Tecartus was successfully manufactured and elicited robust objective response rates regardless of white blood cell or lymphocyte count. CAR expansion within the first month post-infusion was associated with both best response and durable response.
