Tecartus Data Reinforces Efficacy at ASH 2024

Details are as follows:

Abstract #748 Primary Analysis of ZUMA-2 Cohort 3: Brexucabtagene Autoleucel (Brexu-Cel) in Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Who Were Naive to Bruton Tyrosine Kinase Inhibitors (BTKi)  ZUMA-2 is a single-arm, multicenter, open-label Phase II study that investigated leukapheresed adult patients (≥18 years old) with MCL whose disease is refractory to or has relapsed following up to five prior lines of therapy, including anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy and the BKTi ibrutinib or acalabrutinib. Cohort 3 of ZUMA-2 assesses treatment of Tecartus in 86 patients who have not received treatment with a BTKi.

With a median follow-up of 15.5 months (range, 1.4-27.1), the primary endpoint was met with an ORR of 91% (95% CI, 82.5-95.9; P<.0001). Seventy three percent (95% CI, 62.6-82.2) of patients had a CR, 17% (95% CI, 10.1-27.1) had a partial response (PR), 3% (95% CI, 0.7-9.9) had stable disease, and 3% (95% CI, 0.7-9.9) had progressive disease (PD) as best response to Tecartus. This efficacy was durable: Preliminary follow-up shows median duration of all time-to-event endpoints has not been met. The 12-month (95% CI) 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.

No new safety signals were detected, with a low rate of Grade ≥ 3 cytokine release syndrome (CRS) occurring in five patients (6%) and an expected rate of Grade ≥ 3 neurological events (immune effector cell-associated neurotoxicity syndrome [ICANS]), occurring in 18 patients (21%).

Abstract #4388 Five-Year Outcomes of Patients (Pts) With Relapsed/Refractory Mantle Cell Lymphoma (R/R MCL) Treated With Brexucabtagene Autoleucel (Brexu-cel) in ZUMA-2 Cohorts 1 and 2  The abstract features five-year follow-up data from cohort 1 of the ZUMA-2 study. Cohort 1 enrolled 68 patients who received the pivotal dose (2×10 ⁶ anti-CD19 CAR T cells/kg) of Tecartus and received at least two prior lines of therapy. In addition, cohort 2 was designed in 2018 to assess a lower dose (0.5 x 10 ⁶ anti-CD19 CAR T cells/kg) in the same line setting; however, the risk/benefit ratio of the cohort 1 dose was deemed optimal before cohort 2 reached full enrollment. In the primary analysis of cohort 2, 14 patients treated with Tecartus with a median follow-up of 16.0 (13.9-18.0) months demonstrated an ORR of 93% (95% CI, 66.1-99.8) per independent radiology review committee (IRRC); 64% had a CR (95% CI, 35.1-87.2), and 29% had a PR (95% CI, 8.4-58.1).

In the five-year analysis, median follow-up for cohorts 1 and 2 were 67.8 months (58.2-88.6) and 72.3 months (70.1-74.3), respectively. Median (95% CI) investigator-assessed DOR and PFS were 36.5 months (17.7-48.9; n=60; 17 patients in ongoing response, all CR) and 25.3 months (12.7-46.6; n=68) in cohort 1; and 57.5 months (4.7-not estimable [NE]; n=12; 3 patients in ongoing response, all CR) and 29.5 months (3.3-NE; n=14) in cohort 2. Median OS (95% CI) and 60-month OS rates (95% CI) were 46.5 months (24.9- 60.2) and 39% (26.7-50.1) in cohort 1, respectively; and not reached (9.4-NE) and 54% (23.8-76.2) in cohort 2, respectively.

No new safety signals were detected, and no secondary T‑cell malignancies were reported at any time in ZUMA-2

Abstract # 5092  Real-World Outcomes for Brexucabtagene Autoleucel (Brexu-Cel) Treatment in Patients (Pts) With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) by High-Risk Features and Prior Treatments: Updated Evidence From the CIBMTR Registry  This real-world analysis of 242 evaluable adult R/R B-ALL patients treated with Tecartus from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry demonstrated the high effectiveness of CAR T-cell therapy in a broad R/R B-ALL patient population. With a median follow-up of 7.2 months, the CR/CRi (CR with incomplete hematologic recovery) after Tecartus treatment was 80% (95% CI, 75-85; 68% [60-76] for 145 patients not in CR/CRi pre-infusion). Estimated six-month rates (95% CI) of DOR were 67% (58-74; n=192; 66% [51-77] in 99 patients not in CR/CRi pre-infusion), six-month rates of relapse-free survival (RFS) were 55% (95% CI, 48-62; n=242), and six-month rates of OS were 80% (95% CI, 74-84; n=242).

Among all patients (n=242), rates of any grade CRS and ICANS by 100 days were 81% (95% CI, 76-86; 13% Grade ≥3 [95% CI, 9-18]), and 46% (95% CI, 39-52; 24% Grade ≥3 [95% CI, 19-30]), respectively. Day 30 prolonged thrombocytopenia and neutropenia rates were 30% (95% CI, 24-36) and 34% (95% CI, 28-41), respectively.

Abstract #4193 Impact of Disease Burden, CAR-T Expansion, and Mononuclear Cell Recovery on Overall Response and Duration of Response in ZUMA-3 Pivotal Study In the analysis, researchers evaluated clinical and pharmacokinetic/pharmacodynamic data in the context of best response and durability of response among 78 R/R B-ALL patients who received Tecartus in the ZUMA-3 study. 

Tecartus was successfully manufactured from apheresis material and elicited robust rates of objective response regardless of white blood cell or lymphocyte count. Half of the patients who achieved duration of response lasting >12 months had a bone marrow blast percentage of ≥50%, demonstrating the potential of Tecartus to benefit patients regardless of disease burden. Additionally, CAR expansion within the first month post Tecartus infusion is associated with best response as well as durable response, even without persistence of CAR T cells. Recovery of mononuclear cells post infusion also appeared higher in subjects with longer response. These findings have the potential to support treatment decision-making, such as the need for subsequent allogeneic stem cell transplant as consolidation of remission.

“For years, we have seen strong, durable responses with brexu-cel from patients previously exposed to BTKi treatment,” said Dr. Tom van Meerten, lead investigator, University Medical Center Groningen, Netherlands.​ “Patients with high-risk relapsed/refractory mantle cell lymphoma have poor outcomes, so it is encouraging to see positive results even in people who are BTKi-naïve. 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.”

“More than three years after its approval, brexu-cel continues to deliver in relapsed/refractory mantle cell lymphoma,” said Dr. Michael Wang, lead investigator, The University of Texas MD Anderson Cancer Center. “It is encouraging to see these results in a heavily pre-treated population and consistency across both cohorts.”

“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,” said Dr. Kitsada Wudhikarn​, lead investigator, Associate Professor of Medicine, Division of Hematology, Chulalongkorn University, Bangkok, Thailand. “Notably, the high level of effectiveness seen in the patient registry was consistent across prior treatments and most high-risk features. These findings provide further evidence of the substantial utility of brexu-cel in the treatment of this challenging blood cancer.”