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

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 asso...

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Published in:Blood Vol. 133; no. 15; p. 1652
Main Authors: Hay, Kevin A, Gauthier, Jordan, Hirayama, Alexandre V, Voutsinas, Jenna M, Wu, Qian, Li, Daniel, Gooley, Ted A, Cherian, Sindhu, Chen, Xueyan, Pender, Barbara S, Hawkins, Reed M, Vakil, Aesha, Steinmetz, Rachel N, Schoch, Gary, Chapuis, Aude G, Till, Brian G, Kiem, Hans-Peter, Ramos, Jorge D, Shadman, Mazyar, Cassaday, Ryan D, Acharya, Utkarsh H, Riddell, Stanley R, Maloney, David G, Turtle, Cameron J
Format: Journal Article
Language:English
Published: United States 11.04.2019
Subjects:
Adult
Antigens, CD19 - immunology
Disease-Free Survival
Female
Hematopoietic Stem Cell Transplantation
Humans
Immunotherapy, Adoptive - methods
Lymphocyte Depletion
Male
Middle Aged
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - mortality
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma - therapy
Receptors, Chimeric Antigen
Remission Induction - methods
Salvage Therapy - methods
Young Adult
ISSN:1528-0020, 1528-0020
Online Access:Get more information
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Summary: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; < .0001; median OS, 20.0 vs 5.0 months; = .014). In patients who achieved MRD-negative CR by flow cytometry, absence of the index malignant clone by deep sequencing was associated with better EFS ( = .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.
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ISSN:1528-0020
1528-0020
DOI:10.1182/blood-2018-11-883710