KTE-X19 Granted Positive EU Opinion for Relapsed/Refractory MCL

The European Medicines Agency’s Committee for Medicinal Products for Human Use has adopted a positive opinion for KTE-X19 as a treatment in adult patients with relapsed/refractory mantle cell lymphoma who previously received 2 or more lines of systemic therapy, including a BTK inhibitor.

The European Medicines Agency’s Committee for Medicinal Products for Human Use (has adopted a positive opinion for KTE-X19 as a treatment in adult patients with relapsed/refractory mantle cell lymphoma (MCL) who previously received 2 or more lines of systemic therapy, including a BTK inhibitor, according to Kite.1

The recommendation is based on safety and efficacy data with the CAR T-cell therapy from the phase 2 ZUMA-2 trial, which demonstrated that a single infusion of the product led to an 87% objective response rate (ORR) per Independent Radiologic Review Committee in patients with relapsed/refractory disease.2 The complete response (CR) rate with KTE-X19 was 62%.

“This opinion is an important milestone for patients in Europe living with relapsed/refractory MCL,” said Ken Takeshita, MD, global head of Clinical Development at Kite.1 “Kite is committed to bringing the promise of CAR T-cell therapy to patients with hematologic cancers and, pending approval by the European Commission, we hope to bring this innovative treatment option forward for patients in Europe as quickly as possible.”

KTE-X19 is composed of an anti-CD19 single-chain variable fragment with a CD3 zeta T-cell activation domain and a CD28 signaling domain. Circulating tumor cells are separated from autologous immune cells within the manufacturing process.

The single-arm, open-label phase 2 trial enrolled a total of 74 patients who underwent leukapheresis. Five patients did not receive the product; 3 did not due to manufacturing failures, while 2 died from disease progression. Sixty-nine participants underwent conditioning chemotherapy and 68 patients received the CAR T-cell therapy.

A primary efficacy analysis was done on the first 60 patients who enrolled to ZUMA-2. The product was noted to have been effectively manufactured for the majority, or 96%, of patients and it was given to 92%. The median time from leukapheresis to delivery of the CAR T-cell product was 16 days.

The median age of study participants was 65 years and a little more than half, or 57%, of patients were older. Eighty-five percent of patients had stage IV disease, while 56% had intermediate- or high-risk disease. In 69% of patients, the Ki-67 proliferation index was 50% or greater, and 17% harbored TP53 mutations. Around half of patients (54%) had bone marrow involvement and 56% had extranodal disease. Moreover, 59% had classical morphology, 25% had blastoid, and 6% had pleomorphic.

The median number of previous lines of therapy received was 3, with 81% of patients having received 3 or more treatment. The majority of patients had previously been given an anthracycline or bendamustine and all patients had received prior treatment with an anti-CD20 antibody. All patients had been exposed to BTK inhibitors before study start. Moreover, 37% of patients had been on bridging therapy, with 21% having received ibrutinib (Imbruvica). Among those who received bridging therapy, 92% of patients had higher disease burden before CAR T-cell administration versus baseline.

Additional data showed that 40% of patients who initially had a partial remission or achieved stable disease transitioned to CRs; the median time to CR was 3 months. The median duration of response had not been reached at the time that the analysis was conducted. Seventy-eight percent of patients who achieved a CR remained in remission.

The median follow-up was 27.0 months for the first 28 patients who received treatment with KTE-X19 in ZUMA-2. Forty-three percent of patients in this subset remained in remission.

The median progression-free survival (PFS) with the CAR T-cell product had not been reached at the time of the analysis. The PFS rate at 12 months was 61% with KTE-X19, with a tail on the curve (95% CI, 45%-74%). The median overall survival (OS) had also not been reached; the 12-month OS rate was 83% (95% CI, 71%-91%).

With regard to safety, the most frequently reported all-grade treatment-emergent toxicities included pyrexia (94%), neutropenia (87%), thrombocytopenia (74%), anemia (68%), and hypotension (51%). Grade 4 treatment-emergent adverse effects (TEAEs) were neutropenia (69%), thrombocytopenia (35%), hypoxia (9%), and hypotension (3%). Two grade 5 toxicities were reported: pneumonia associated with conditioning treatment and staphylococcal bacteremia because of both post-conditioning therapy and the CAR T-cell infusion. Moreover, 91% of participants experienced all-grade cytokine release syndrome.

Additional insights regarding KTE-X19 in ZUMA-2 were presented during the 2020 ASCO Virtual Scientific Program. Here, the pharmacodynamic profile of the CAR T-cell product was linked with efficacy and treatment-related neurological events.3

Moreover, when the agent was compared with other approved options, it was found to show comparable pharmacologic and clinical outcomes in patients with high-risk MCL characteristics versus lower-risk characteristics defined by tumor protein TP53 mutation or high Ki-67 proliferation index.

In July 2020, brexucabtagene autoleucel (Tecartus) was approved by the FDA for use in adult patients with relapsed/refractory MCL based on data from ZUMA-2.


  1. European CHMP adopts positive opinion for Kite’s KTE-X19 for the treatment of relapsed or refractory mantle cell lymphoma. News release. Kite. October 16, 2020. Accessed October 16, 2020. https://bit.ly/2HcbUWZ.
  2. Wang ML, Munoz J, Goy A, et al. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL): results of the phase 2 ZUMA-2 study. Blood. 2019;134(suppl 1):754. doi:10.1182/blood-2019-126064
  3. Wang M, Rossi JM, Munoz J, et al. Product characteristics and pharmacologic profile of KTE-X19 in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL) in the phase II registrational ZUMA-2 trial. J Clin Oncol. 2020;38(suppl 15):3023. doi:10.1200/JCO.2020.38.15_suppl.3023