Long-term outcomes and predictors of early response, late relapse, and survival for patients treated with bispecific LV20.19 CAR T-cells. Am J Hematol 2022 Dec;97(12):1580-1588
Date
09/08/2022Pubmed ID
36068950DOI
10.1002/ajh.26718Scopus ID
2-s2.0-85138335080 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
We previously reported results of a first-in-human trial of bispecific LV20.19 chimeric antigen receptor T-cell (CAR-T) therapy, demonstrating high response rates in patients with relapsed, refractory (R/R) B-cell malignancies. We now report two-year survival outcomes and predictors of early response, late relapse, and survival. Patients from the previously reported phase 1 dose escalation and expansion trial of LV20.19 CAR-T therapy (NCT03019055) treated at target dose of 2.5 × 106 cells/kg (n = 16) were included in this updated analysis. Two-year progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. The relationship of in-vivo CAR-T expansion, tumor burden, and effector: target ratio on early response (day 28) and late relapse (>180 days post-CAR-T) were assessed. Exact log-rank testing was performed to evaluate the impacts of clinical variables on survival outcomes. With a median of 31 months (range 27-40) of follow-up, two-year PFS and OS were 44% and 69%. Median PFS and OS were 15.6 months and not reached, respectively. For CAR-naïve large B-cell lymphoma patients (n = 8), two-year PFS and OS were 50% and 75%. No patient with progression experienced dual target antigen (CD19 or CD20) loss on post-relapse biopsy. Lower in vivo expansion was strongly associated with late relapse. Early treatment response was impeded by high metabolic tumor volume and low effector: target ratio. Bridging therapy and higher absolute lymphocyte count on day of CAR-T infusion were associated with inferior survival outcomes. In conclusion, this initial trial of LV20.19 CAR-T demonstrates a signal for favorable long-term outcomes for patients with R/R B-cell malignancies.
Author List
Zurko JC, Fenske TS, Johnson BD, Bucklan D, Szabo A, Xu H, Chaney K, Hamadani M, Hari P, Shah NNAuthors
Daniel Bucklan MD Assistant Professor in the Radiology department at Medical College of WisconsinMehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin
Nirav N. Shah MD Associate Professor in the Medicine department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Antigens, CD19Humans
Immunotherapy, Adoptive
Neoplasm Recurrence, Local
Receptors, Antigen, T-Cell
T-Lymphocytes
