KTE-X19 active in MCL

The survival outcomes of patients with relapsed and/or refractory mantle-cell lymphoma (MCL) after receiving BTK inhibitors are poor; therefore, new treatment options are needed for these patients. Chimeric antigen receptor (CAR) T cell therapies targeting CD19 have demonstrated efficacy in several subtypes of B cell lymphomas, although limited results in patients with MCL have been reported. Now data from the ZUMA-2 trial reveal promising activity of the anti-CD19 CAR T cell product KTE-X19 against MCL.

In ZUMA-2, KTE-X19 was successfully manufactured for 71 of 74 patients with relapsed and/or refractory MCL. A high content of leukaemic blasts in peripheral blood has been proposed as the cause of failed manufacturing of CAR T cells because it results in proportionally low numbers of non-exhausted T cells in the starting cell population. During the manufacturing of KTE-X19, circulating CD19+ malignant cells were removed in order to address this issue by reducing the potential activation and exhaustion of anti-CD19 CAR T cells in the ex vivo portion of the process.

KTE-X19 was administered to 68 patients. Among 60 patients with at least 7 months of follow-up monitoring, the objective response rate (ORR) was 93%, with a complete response (CR) rate of 67%. ORRs were consistent across patient subgroups, including those with high-risk disease. At a median of 12.3 months, 57% of the 60 patients and 78% of those with a CR had an ongoing response. Of note, all these patients received a single infusion of KTE-X19.

Exploratory analyses of minimal residual disease revealed that 24 of 29 patients (83%) and 15 of 19 patients (79%) had no detectable residual disease at 4 weeks and 6 months, respectively. The 12-month progression-free survival and overall survival estimates were 61% and 83%, respectively.

Grade ≥3 adverse events (AEs) occurred in 99% of 68 patients, the most common of which were cytopenias (94%) and infections (32%). Grade 1–2 and ≥3 cytokine-release syndrome (CRS) occurred in 76% and 15% of patients, respectively. Two infectious AEs were fatal. All CRS events resolved with treatment within a median of 11 days. Grade 1–2 and ≥3 neurological AEs occurred in 32% and 31% of patients. These events resolved with treatment in 37 of 43 patients (86%) at a median of 12 days. No deaths resulted from CRS or neurological AEs.

In conclusion, the results of ZUMA-2 indicate that patients with relapsed and/or refractory MCL can derive clinical benefit from CAR T cells, although at the expense of a high risk of toxicities. The majority of AEs reported in this trial were manageable. Moreover, the toxicity profile of KTE-X19 was deemed similar to that of the CAR T cell products used to treat patients with other B cell lymphomas. Longer follow-up results will help to determine the durability of these responses; in addition, the results of other trials of CAR T cell products in patients with MCL are eagerly awaited.


Original article

  1. Wang, M. et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N. Engl. J. Med. 383, 1331–1342 (2020)

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Diana Romero.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Romero, D. KTE-X19 active in MCL. Nat Rev Clin Oncol 17, 336 (2020). https://doi.org/10.1038/s41571-020-0373-3

Download citation


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing