Priority review KTE-X19 for R/R mantle cell lymphoma

May 2020 Pharma News Marjolein Groot

Mantle cell lymphoma is a form of lymphatic cancer and a non-Hodgkin lymphoma. Mantle cell lymphoma patients that are refractory or relapsing and show progression of their illness after receiving Bruton’s tyrosine kinase (BTK)-inhibitor therapy, often have a dismal prognosis. For these patients, treatment with KTE-X19, that is currently under investigation, could provide a solution. KTE-X19 is an autologous anti-CD19 chimeric antigen receptor (CAR)-T therapy.

ZUMA-2

Treatment with KTE-X19 was investigated in the multicentre, phase 2-ZUMA-trial including 74 patients with refractory/relapsing (R/R) mantle cell lymphoma. These patients were R/R after receiving a minimum of 5 therapies, including cBTK-inhibitor therapy.

After going through leukapheresis and bridging therapy if needed, the patients receiving conditioning chemotherapy and a single infusion of KTE-X19 (2*106 CAR-T cells per kg body weights). From the patients that were included, 68 received KTE-X19. The first 60 patients of this group were analysed.

Major response

From the patients that were analysed 93% (95% CI: 84-98) showed an objective response and 67% (95% CI: 53-78%) a complete response. At the time of follow up, 12.3 months on average after treatment (within 7-32.3 month) 57% of the 60 patients were in remission. After a year, the progression-free survival (PFS) was 61% and overall survival (OS) was 83%.

In 94% of patients, cytopenia occurred (stage 3/4) and in 32% an infection (stage 3/4). Moreover, 15% of patients experienced cytokine release syndrome (grade 3/4) and 31% of patients a neurological event. Two patients passed away due to infectious adverse events.

Priority review

The FDA accepted the Biologics Licence Applications of KTE-X19 and assigned priority review to the pharmaceutical. This entails that the FDA expects that KTE-X19 will provide a significant improvement in safety or efficacy of the treatment of R/R mantle cell lymphoma. The EMA has also recently given out marketing authorisation for KTE-X19 in the EU. Registration is expected in December 2020.

Sources

  1. Wang M, Munoz J, Goy A, et al. (2020). KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. New England Journal of Medicine382(14), 1331-1342.
  2. www.gilead.com/

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