Tecartus CAR T-cell therapy demonstrates 78% complete response rate and 90% overall response rate in largest real-world evidence analysis for r/r mantle cell lymphoma

Which show that outcomes of Tecartus therapy had consistent high complete response (CR) and overall response rates (ORR), regardless of type of prior treatment, including: Bruton's tyrosine kinase inhibitor (BTKi), bendamustine or autologous hematopoietic cell transplant (autoHCT). Higher CR was seen when Tecartus was given as second-and-third-line compared to later lines of treatment. The data are being presented orally at the 2023 American Society of Clinical Oncology Annual Meeting (ASCO) (Abstract #7507).

“Mantle cell lymphoma is an aggressive and rare type of lymphoma, and once patients relapse or fail to respond, it is difficult to treat, with many patients undergoing four or more lines of treatment,” said Swetha Kambhampati, MD, lead investigator, City of Hope assistant professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation. “It is encouraging to see that these real-world data reinforce brexucabtagene autoleucel’s safety and efficacy, and outcomes are consistent regardless of prior course of therapy and suggest its potential benefit when used earlier in lines of treatment for relapsed/refractory patients.”

Prospective data from 380 patients registered in the Center for International Blood and Marrow Transplant Research (CIBMTR) observational database receiving Tecartus for R/R MCL from 73 U.S. treatment centers were included in this analysis; these data from standard-of-care practice were collected for the post-authorization safety study (PASS) for Tecartus in the US, which completed enrollment in December 2022. Patients had a median of four lines of prior therapy; prior to infusion, 87% were BTKi-exposed, 56% received bendamustine, and 30% received autoHCT. Median time from leukapheresis to infusion (also referred to as vein-to-vein time) was 28 days, during which time 46% received bridging therapy.

With median follow-up of 12 months, ORR was 90%, which was similar to ZUMA-2 results and high CR (78%) was seen in patients who received Tecartus. Additionally, at 12 months, duration of response (DOR) (since earliest CR/partial response), progression-free survival (PFS) and overall survival (OS) rates were 64%, 61% and 74% respectively. Grade 3 or higher cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) (based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria) incidence were 10% and 28% respectively.

In a multivariate analysis of patients who received Tecartus in earlier lines of therapy (1-2 vs greater than 3 prior lines of therapy), the data showed an ORR of 94% and a CR of 88%. The multivariate analysis assessed outcomes based on prior therapy; findings show that real-world effectiveness and safety outcomes with Tecartus in patients with R/R MCL are consistent regardless of prior treatment. In BTKi-naïve patients, effectiveness (ORR 92%, CR 83%) and safety outcomes are consistent when compared with prior BTKi-treated patients. In patients with prior bendamustine use, effectiveness remained consistent and prior bendamustine use was associated with a reduced risk of grade greater than 3 immune effector cell-associated neurotoxicity syndrome (ICANS (odds ratio [OR] 0.50; 95% confidence interval [CI], 0.30–0.84) and increased risk of prolonged thrombocytopenia (OR 1.98; 95% CI, 1.11–3.53). Within the multivariate analysis, PFS was improved in patients with prior autoHCT compared to those without prior autoHCT (hazard ratio [HR] 0.56; 95% CI, 0.35–0.88).

“Unfortunately for patients living with mantle cell lymphoma, outcomes are poor and there are limited treatment options," said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development. “Data from this real-world registry suggest that earlier treatment with Tecartus may confer better outcomes in these difficult-to-treat patients compared to later lines and should be evaluated further in additional studies.”

About ZUMA-2 Study: ZUMA-2 is a single-arm, multicenter, open-label Phase II study involving 74 enrolled/leukapheresed adult patients ( greater than 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 BTK inhibitors ibrutinib or acalabrutinib. The objectives of the study are to evaluate the efficacy (60 patients) and safety (68 patients) after a single infusion of KTE X19 in this patient population. The primary endpoint for the study is objective response rate in this trial is defined as the combined rate of complete responses and partial responses as assessed by an Independent Radiology Review Committee. Secondary endpoints include duration of response, best objective response, progression-free survival, overall survival, incidence of adverse events, incidence of anti-CD19 CAR antibodies, levels of anti-CD19 CAR T cells in blood, levels of cytokines in serum, and changes over time in the EQ-5D scale score and visual analogue scale score. The study is ongoing.

About KT-US-472-5655 PASS For a period of 15 years post-approval, the FDA and other National Health Authorities require a mechanism to follow CAR T-cell therapy patients to assess safety and efficacy outcomes. The approach for this requirement for Tecartus was the development of a prospective, non-interventional cohort study. KT-US-472-5655 is a PASS reviewed and approved by the FDA and by the National Marrow Donor Program (NMDP) central Institutional Review Board and administered by the Cellular Immunotherapy Data Resource infrastructure managed by the CIBMTR. The primary objective of the study is to evaluate the development of subsequent neoplasms after administration of Tecartus for treatment of R/R MCL and R/R adult ALL. Secondary objectives include evaluation of OS, causes of death, relapse or progression of the primary disease, DOR, minimal residual disease (MRD) (for ALL only), subsequent allogeneic hematopoietic cell transplantation (for ALL only), incidence and severity of cytokine release syndrome, neurological events, serious infections, prolonged cytopenia and hypogammaglobulinemia, causes of death, and pregnancy outcomes. The accrual goal for the PASS study was 500 patients with R/R MCL, which was completed in December 2022. Enrollment for R/R ALL is ongoing.