Details

Autor(en) / Beteiligte

• Ghorashian, Sara
• Lucchini, Giovanna
• Richardson, Rachel
• Nguyen, Kyvi
• Terris, Craig
• Guvenel, Aleks
• Oporto-Espuelas, Macarena
• Yeung, Jenny
• Pinner, Danielle
• Chu, Jan
• Williams, Lindsey
• Ko, Ka-Yuk
• Walding, Chloe
• Watts, Kelly
• Inglott, Sarah
• Thomas, Rebecca
• Connor, Christopher
• Adams, Stuart
• Gravett, Emma
• Gilmour, Kimberly
• Lal, Alka
• Kunaseelan, Sangeetha
• Popova, Bilyana
• Lopes, Andre
• Ngai, Yenting
• Hackshaw, Allan
• Kokalaki, Evangelia
• Carulla, Milena Balasch
• Mullanfiroze, Khushnuma
• Lazareva, Arina
• Pavasovic, Vesna
• Rao, Anupama
• Bartram, Jack
• Vora, Ajay
• Chiesa, Robert
• Silva, Juliana
• Rao, Kanchan
• Bonney, Denise
• Wynn, Robert
• Pule, Martin
• Hough, Rachael
• Amrolia, Persis J

Titel

CD19/CD22 targeting with cotransduced CAR T cells to prevent antigen-negative relapse after CAR T-cell therapy for B-cell ALL

Ist Teil von

• Blood, 2024-01, Vol.143 (2), p.118-123

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• CD19-negative relapse is a leading cause of treatment failure after chimeric antigen receptor (CAR) T-cell therapy for acute lymphoblastic leukemia. We investigated a CAR T-cell product targeting CD19 and CD22 generated by lentiviral cotransduction with vectors encoding our previously described fast-off rate CD19 CAR (AUTO1) combined with a novel CD22 CAR capable of effective signaling at low antigen density. Twelve patients with advanced B-cell acute lymphoblastic leukemia were treated (CARPALL [Immunotherapy with CD19/22 CAR Redirected T Cells for High Risk/Relapsed Paediatric CD19+ and/or CD22+ Acute Lymphoblastic Leukaemia] study, NCT02443831), a third of whom had failed prior licensed CAR therapy. Toxicity was similar to that of AUTO1 alone, with no cases of severe cytokine release syndrome. Of 12 patients, 10 (83%) achieved a measurable residual disease (MRD)-negative complete remission at 2 months after infusion. Of 10 responding patients, 5 had emergence of MRD (n = 2) or relapse (n = 3) with CD19- and CD22-expressing disease associated with loss of CAR T-cell persistence. With a median follow-up of 8.7 months, there were no cases of relapse due to antigen-negative escape. Overall survival was 75% (95% confidence interval [CI], 41%-91%) at 6 and 12 months. The 6- and 12-month event-free survival rates were 75% (95% CI, 41%-91%) and 60% (95% CI, 23%-84%), respectively. These data suggest dual targeting with cotransduction may prevent antigen-negative relapse after CAR T-cell therapy.