Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Journal of Clinical Oncology Année : 2023

Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study

Andre Goy
Frederick Locke
Caron Jacobson
Brian Hill
  • Fonction : Auteur
John Timmerman
  • Fonction : Auteur
Houston Holmes
  • Fonction : Auteur
Samantha Jaglowski
  • Fonction : Auteur
Ian Flinn
Peter Mcsweeney
  • Fonction : Auteur
David Miklos
John Pagel
Marie José Kersten
Krimo Bouabdallah
  • Fonction : Auteur
Rashmi Khanal
  • Fonction : Auteur
Max Topp
Amer Beitinjaneh
Weimin Peng
  • Fonction : Auteur
Xiang Fang
  • Fonction : Auteur
Rhine Shen
  • Fonction : Auteur
Rubina Siddiqi
Ioana Kloos
  • Fonction : Auteur

Résumé

PURPOSE Brexucabtagene autoleucel (KTE-X19) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). Outcomes after a 3-year follow-up in the pivotal ZUMA-2 study of KTE-X19 in relapsed/refractory MCL are reported, including for subgroups by prior therapy (bendamustine and type of Bruton tyrosine kinase inhibitor [BTKi]) or high-risk characteristics. METHODS Patients with relapsed/refractory MCL (one to five prior therapies, including prior BTKi exposure) received a single infusion of KTE-X19 (2 × 10 6 CAR T cells/kg). RESULTS After a median follow-up of 35.6 months, the objective response rate among all 68 treated patients was 91% (95% CI, 81.8 to 96.7) with 68% complete responses (95% CI, 55.2 to 78.5); medians for duration of response, progression-free survival, and overall survival were 28.2 months (95% CI, 13.5 to 47.1), 25.8 months (95% CI, 9.6 to 47.6), and 46.6 months (95% CI, 24.9 to not estimable), respectively. Post hoc analyses showed that objective response rates and ongoing response rates were consistent among prespecified subgroups by prior BTKi exposure or high-risk characteristics. In an exploratory analysis, patients with prior bendamustine benefited from KTE-X19, but showed a trend toward attenuated T-cell functionality, with more impact of bendamustine given within 6 versus 12 months of leukapheresis. Late-onset toxicities were infrequent; only 3% of treatment-emergent adverse events of interest in ZUMA-2 occurred during this longer follow-up period. Translational assessments revealed associations with long-term benefits of KTE-X19 including high-peak CAR T-cell expansion in responders and the predictive value of minimal residual disease for relapse. CONCLUSION These data, representing the longest follow-up of CAR T-cell therapy in patients with MCL to date, suggest that KTE-X19 induced durable long-term responses with manageable safety in patients with relapsed/refractory MCL and may also benefit those with high-risk characteristics.

Domaines

Cancer

Dates et versions

hal-04067687 , version 1 (13-04-2023)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Michael Wang, Javier Munoz, Andre Goy, Frederick Locke, Caron Jacobson, et al.. Three-Year Follow-Up of KTE-X19 in Patients With Relapsed/Refractory Mantle Cell Lymphoma, Including High-Risk Subgroups, in the ZUMA-2 Study. Journal of Clinical Oncology, 2023, 41 (3), pp.555-567. ⟨10.1200/JCO.21.02370⟩. ⟨hal-04067687⟩
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