Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy.

Autor:	Hay KA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Gauthier J; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Hirayama AV; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Voutsinas JM; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Wu Q; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Li D; Juno Therapeutics, Seattle, WA; and., Gooley TA; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Cherian S; Department of Laboratory Medicine and., Chen X; Department of Laboratory Medicine and., Pender BS; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Hawkins RM; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Vakil A; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Steinmetz RN; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Schoch G; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA., Chapuis AG; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Till BG; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Kiem HP; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Ramos JD; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Shadman M; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Cassaday RD; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Acharya UH; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Riddell SR; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Maloney DG; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA., Turtle CJ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.; Department of Medicine, University of Washington, Seattle, WA.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2019 Apr 11; Vol. 133 (15), pp. 1652-1663. Date of Electronic Publication: 2019 Feb 06.
DOI:	10.1182/blood-2018-11-883710
Abstrakt:	Autologous T cells engineered to express a CD19-specific chimeric antigen receptor (CAR) have produced impressive minimal residual disease-negative (MRD-negative) complete remission (CR) rates in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL). However, the factors associated with durable remissions after CAR T-cell therapy have not been fully elucidated. We studied patients with relapsed/refractory B-ALL enrolled in a phase 1/2 clinical trial evaluating lymphodepletion chemotherapy followed by CD19 CAR T-cell therapy at our institution. Forty-five (85%) of 53 patients who received CD19 CAR T-cell therapy and were evaluable for response achieved MRD-negative CR by high-resolution flow cytometry. With a median follow-up of 30.9 months, event-free survival (EFS) and overall survival (OS) were significantly better in the patients who achieved MRD-negative CR compared with those who did not (median EFS, 7.6 vs 0.8 months; P < .0001; median OS, 20.0 vs 5.0 months; P = .014). In patients who achieved MRD-negative CR by flow cytometry, absence of the index malignant clone by IGH deep sequencing was associated with better EFS ( P = .034). Stepwise multivariable modeling in patients achieving MRD-negative CR showed that lower prelymphodepletion lactate dehydrogenase concentration (hazard ratio [HR], 1.38 per 100 U/L increment increase), higher prelymphodepletion platelet count (HR, 0.74 per 50 000/μL increment increase), incorporation of fludarabine into the lymphodepletion regimen (HR, 0.25), and allogeneic hematopoietic cell transplantation (HCT) after CAR T-cell therapy (HR, 0.39) were associated with better EFS. These data allow identification of patients at higher risk of relapse after CAR T-cell immunotherapy who might benefit from consolidation strategies such as allogeneic HCT. This trial was registered at www.clinicaltrials.gov as #NCT01865617. (© 2019 by The American Society of Hematology.)
Databáze:	MEDLINE
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