KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma.
The New England journal of medicine
Adult; Aged; Antigens, CD19; Antineoplastic Agents; Combined Modality Therapy; Humans; Immunotherapy, Adoptive; Infusions, Intravenous; Leukapheresis; Lymphoma, Mantle-Cell; Middle Aged; Receptors, Chimeric Antigen; Recurrence; Survival Analysis; T-Lymphocytes; Vidarabine
BACKGROUND: Patients with relapsed or refractory mantle-cell lymphoma who have disease progression during or after the receipt of Bruton's tyrosine kinase (BTK) inhibitor therapy have a poor prognosis. KTE-X19, an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, may have benefit in patients with relapsed or refractory mantle-cell lymphoma.
METHODS: In a multicenter, phase 2 trial, we evaluated KTE-X19 in patients with relapsed or refractory mantle-cell lymphoma. Patients had disease that had relapsed or was refractory after the receipt of up to five previous therapies; all patients had to have received BTK inhibitor therapy previously. Patients underwent leukapheresis and optional bridging therapy, followed by conditioning chemotherapy and a single infusion of KTE-X19 at a dose of 2×10
RESULTS: A total of 74 patients were enrolled. KTE-X19 was manufactured for 71 patients and administered to 68. The primary efficacy analysis showed that 93% (95% confidence interval [CI], 84 to 98) of the 60 patients in the primary efficacy analysis had an objective response; 67% (95% CI, 53 to 78) had a complete response. In an intention-to-treat analysis involving all 74 patients, 85% had an objective response; 59% had a complete response. At a median follow-up of 12.3 months (range, 7.0 to 32.3), 57% of the 60 patients in the primary efficacy analysis were in remission. At 12 months, the estimated progression-free survival and overall survival were 61% and 83%, respectively. Common adverse events of grade 3 or higher were cytopenias (in 94% of the patients) and infections (in 32%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 15% and 31% of patients, respectively; none were fatal. Two grade 5 infectious adverse events occurred.
CONCLUSIONS: KTE-X19 induced durable remissions in a majority of patients with relapsed or refractory mantle-cell lymphoma. The therapy led to serious and life-threatening toxic effects that were consistent with those reported with other CAR T-cell therapies. (Funded by Kite, a Gilead company; ZUMA-2 ClinicalTrials.gov number, NCT02601313.).
Wang, Michael; Munoz, Javier; Goy, Andre; Locke, Frederick L; Jacobson, Caron A; Hill, Brian T; Timmerman, John M; Holmes, Houston; Jaglowski, Samantha; Flinn, Ian W; McSweeney, Peter A; Miklos, David B; Pagel, John M; Kersten, Marie-Jose; Milpied, Noel; Fung, Henry; Topp, Max S; Houot, Roch; Beitinjaneh, Amer; Peng, Weimin; Zheng, Lianqing; Rossi, John M; Jain, Rajul K; Rao, Arati V; and Reagan, Patrick M, "KTE-X19 CAR T-Cell Therapy in Relapsed or Refractory Mantle-Cell Lymphoma." (2020). Articles, Abstracts, and Reports. 3100.