Portal de investigación
Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Roddie, C
- Sandhu, KS
- Tholouli, E
- Logan, AC
- Shaughnessy, P
- Barba, P
- Ghobadi, A
- Yallop, D
- Abedi, M
- Pantin, JM
- Yared, JA
- Beitinjaneh, AM
- Chaganti, S
- Hodby, K
- Menne, T
- Arellano, ML
- Malladi, R
- Shah, BD
- Mountjoy, L
- O'Dwyer, KM
- Peggs, KS
- Lao-Sirieix, P
- Zhang, YY
- Brugger, W
- Braendle, E
- Pule, M
- Bishop, MR
- DeAngelo, DJ
- Park, JH
- Jabbour, E
Grupos
Abstract
Background Obecabtagene autoleucel (obe-cel) is an autologous 41BB-zeta anti-CD19 chimeric antigen receptor (CAR) T-cell therapy which uses an intermediate-affinity CAR to reduce toxic effects and improve persistence. Methods We conducted a phase 1b-2 multicenter study of obe-cel in adults (>= 18 years of age) with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). The main cohort, cohort 2A, included patients with morphologic disease; patients in cohort 2B had measurable residual disease. The primary end point was overall remission (complete remission or complete remission with incomplete hematologic recovery) in cohort 2A. Secondary end points included event-free survival, overall survival, and safety. Results Of the 153 enrolled patients, 127 (83.0%) received at least one infusion of obe-cel and were evaluable. In cohort 2A (94 patients; median follow-up, 20.3 months), overall remission occurred in 77% (95% confidence interval [CI], 67 to 85), with complete remission in 55% (95% CI, 45 to 66) and complete remission with incomplete hematologic recovery in 21% (95% CI, 14 to 31). The prespecified null hypotheses of overall remission (<= 40%) and complete remission (<= 20%) were rejected (P<0.001). In the 127 patients who received at least one obe-cel infusion (median follow-up, 21.5 months), the median event-free survival was 11.9 months (95% CI, 8.0 to 22.1); estimated 6- and 12-month event-free survival was 65.4% and 49.5%, respectively. The median overall survival was 15.6 months (95% CI, 12.9 to not evaluable); estimated 6- and 12-month overall survival was 80.3% and 61.1%, respectively. Grade 3 or higher cytokine release syndrome developed in 2.4% of the patients, and grade 3 or higher immune effector cell-associated neurotoxicity syndrome developed in 7.1% of the patients. Conclusions Obe-cel resulted in a high incidence of durable response among adults with relapsed or refractory B-cell ALL, with a low incidence of grade 3 or higher immune-related toxic effects. (Funded by Autolus Therapeutics; FELIX ClinicalTrials.gov number, NCT04404660.) Obecabtagene Autoleucel in Refractory Adult ALL A CD19-specific CAR T-cell therapy with intermediate affinity for CD19 produced a response in 77% of adults with refractory disease. Overall survival was 61% at 12 months, and serious toxic effects were rare.
Datos de la publicación
- ISSN/ISSNe:
- 0028-4793, 1533-4406
- Tipo:
- Article
- Páginas:
- 2219-2230
- PubMed:
- 39602653
- Factor de Impacto:
- 24,907 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
NEW ENGLAND JOURNAL OF MEDICINE MASSACHUSETTS MEDICAL SOC
Citas Recibidas en Web of Science: 197
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Cita
Roddie C,Sandhu KS,Tholouli E,Logan AC,Shaughnessy P,Barba P,Ghobadi A,GUERREIRO M,Yallop D,Abedi M,Pantin JM,Yared JA,Beitinjaneh AM,Chaganti S,Hodby K,Menne T,Arellano ML,Malladi R,Shah BD,Mountjoy L,O'Dwyer KM,Peggs KS,Lao P,Zhang YY,Brugger W,Braendle E,Pule M,Bishop MR,DeAngelo DJ,Park JH,Jabbour E. Obecabtagene Autoleucel in Adults with B-Cell Acute Lymphoblastic Leukemia. N Engl J Med. 2024. 391. (23):p. 2219-2230. IF:78,500. (1).