Safety and Efficacy of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)
Blood
; 138:3823, 2021.
Article
in English
| EMBASE | ID: covidwho-1582409
ABSTRACT
INTRODUCTION We have previously described AUTO1, a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR-T immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL. Cumulatively, this data confirms the intended function of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR-T therapy has been explored in indolent lymphomas such as follicular (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity including Grade 3-4 ICANS has been reported. We have initiated testing of AUTO1 in the setting of indolent and high-grade B-NHL and CLL (NCT02935257). METHODS Manufacturing CAR T-cell products were generated using a semi-automated closed process from non-mobilised leukapheresate. Study design:
Subjects ≥ 16y underwent lymphodepletion with fludarabine (30mg/m 2 x3) and cyclophosphamide (60mg/kg x1) prior to AUTO1 infusion, with the exception of the DLBCL cohort who additionally received a single dose of pembrolizumab (200mg) on day -1 to potentiate CAR-T expansion. AUTO1 dose varies based on the indication. Split dosing of 230 x10
anakinra; CD19, antigen; cyclophosphamide; dexamethasone; endogenous, compound; fludarabine; pembrolizumab; unclassified, drug; adult; apheresis; cancer, patient; cancer, recurrence; cancer, resistance; cancer, staging; chimeric, antigen, receptor, T-cell; chronic, lymphatic, leukemia; clinical, article; cohort, analysis; conference, abstract; controlled, study; coronavirus, disease, 2019; diffuse, large, B, cell, lymphoma; disease, burden; disease, free, survival; drug, combination; drug, safety; drug, therapy; drug, tolerability; employment; engraftment; feasibility, study; female; follow, up; human; incidence; male; mantle, cell, lymphoma; middle, aged; positron, emission, tomography-computed, tomography; remission
Full text:
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Blood
Year:
2021
Document Type:
Article
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