A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma.
J Hematol Oncol
; 11(1): 141, 2018 12 20.
Article
en En
| MEDLINE
| ID: mdl-30572922
ABSTRACT
BACKGROUND:
Chimeric antigen receptor (CAR) T cell therapy has demonstrated proven efficacy in some hematologic cancers. We evaluated the safety and efficacy of LCAR-B38M, a dual epitope-binding CAR T cell therapy directed against 2 distinct B cell maturation antigen epitopes, in patients with relapsed/refractory (R/R) multiple myeloma (MM).METHODS:
This ongoing phase 1, single-arm, open-label, multicenter study enrolled patients (18 to 80 years) with R/R MM. Lymphodepletion was performed using cyclophosphamide 300 mg/m2. LCAR-B38M CAR T cells (median CAR+ T cells, 0.5 × 106 cells/kg [range, 0.07 to 2.1 × 106]) were infused in 3 separate infusions. The primary objective is to evaluate the safety of LCAR-B38M CAR T cells; the secondary objective is to evaluate the antimyeloma response of the treatment based on the general guidelines of the International Myeloma Working Group.RESULTS:
At data cutoff, 57 patients had received LCAR-B38M CAR T cells. All patients experienced ≥ 1 adverse events (AEs). Grade ≥ 3 AEs were reported in 37/57 patients (65%); most common were leukopenia (17/57; 30%), thrombocytopenia (13/57; 23%), and aspartate aminotransferase increased (12/57; 21%). Cytokine release syndrome occurred in 51/57 patients (90%); 4/57 (7%) had grade ≥ 3 cases. One patient reported neurotoxicity of grade 1 aphasia, agitation, and seizure-like activity. The overall response rate was 88% (95% confidence interval [CI], 76 to 95); 39/57 patients (68%) achieved a complete response, 3/57 (5%) achieved a very good partial response, and 8/57 (14%) achieved a partial response. Minimal residual disease was negative for 36/57 (63%) patients. The median time to response was 1 month (range, 0.4 to 3.5). At a median follow-up of 8 months, median progression-free survival was 15 months (95% CI, 11 to not estimable). Median overall survival for all patients was not reached.CONCLUSIONS:
LCAR-B38M CAR T cell therapy displayed a manageable safety profile and demonstrated deep and durable responses in patients with R/R MM. TRIAL REGISTRATION ClinicalTrials.gov , NCT03090659 ; Registered on March 27, 2017, retrospectively registered.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígeno de Maduración de Linfocitos B
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Receptores Quiméricos de Antígenos
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Mieloma Múltiple
Tipo de estudio:
Clinical_trials
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Guideline
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
J Hematol Oncol
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
Año:
2018
Tipo del documento:
Article
País de afiliación:
China