EARLY SAFETY AND EFFICACY FINDINGS OF AUTO1 (CAT19), A FAST-OFF RATE CD19 CAR, IN RELAPSED /REFRACTORY INDOLENT B CELL LYMPHOMAS
Author(s): ,
Claire Roddie
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Juliana Dias
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Maeve O'reilly
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Amaia Cadinanos Garai
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Leticia Bosshard
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Mahnaz Abbasian
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Mark Lowdell
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Maria Marzolini
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Leigh Wood
Affiliations:
Dept Haematology,University College London Hospitals,London,United Kingdom
,
Graham Wheeler
Affiliations:
UCL Cancer Trials Centre,University College London,London,United Kingdom
,
Joanna Olejnik
Affiliations:
UCL Cancer Trials Centre,University College London,London,United Kingdom
,
Laura Clifton-Hadley
Affiliations:
UCL Cancer Trials Centre,University College London,London,United Kingdom
,
Bilyana Popova
Affiliations:
UCL Cancer Trials Centre,University College London,London,United Kingdom
,
Victoria Spanswick
Affiliations:
UCL Cancer Institute,University College London,London,United Kingdom
,
Helen Lowe
Affiliations:
UCL Cancer Institute,University College London,London,United Kingdom
,
Leah Ensell
Affiliations:
UCL Cancer Institute,University College London,London,United Kingdom
,
John Hartley
Affiliations:
UCL Cancer Institute,University College London,London,United Kingdom
,
Farzin Farzaneh
Affiliations:
Kings College London,London,United Kingdom
,
David Linch
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
,
Martin Pule
Affiliations:
Research Department of Haematology,University College London,London,United Kingdom
Karl Peggs
Affiliations:
Dept Haematology,University College London Hospitals,London,United Kingdom
EHA Library. Roddie C. 06/09/21; 325546; EP788
Claire Roddie
Claire Roddie
Contributions
Abstract
Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP788

Type: E-Poster Presentation

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background
We have previously described AUTO1 (CAT19), a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR T-cell 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 fucntion of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR therapy has been explored in indolent lymphomas such as follicluar (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity inluding Grade 3-4 ICANS has been reported.

Aims
We have initiated testing of AUTO1 (CAT19) in the setting of indolent B-cell lymphoma (NCT02935257).

Methods
Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised leucapheresate. Study design: subjects>/=16y underwent lymhpodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by a single CAR T-cell infusion of 200 x10^6 CD19 CAR T-cells. Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months.

Results
As of 18 February 2021, we recruited 10 patients of median age 57 years (range 39-68y), 7 with FL and 3 with MCL. Patients had received a median of 3 prior lines (range 2-5) and all patients had stage III/IV disease at screening. Apheresis and product manufacture was successful in all 10 patients and 9 patients were infused: 7 with FL and 2 with MCL. Grade1 CRS was reported in 4/9 and Grade 2 CRS in 1/9. 1/9 developed MAS which resolved with anakinra/dexamethasone. No ICANS was observed on study. Excellent CAR engraftment was observed and 9/9 patients were in CMR by 18FDG PET-CT post-treatment. At a median of 3.1 months (range 1-5.6m), 8/9 patients are in ongoing remission. One patient died in CMR at month 5.6 of COVID-19.

Conclusion
AUTO1 (CAT19) has a tolerable safety profile in adult patients with r/r low grade B-cell lymphoma despite high disease burden. Early data shows 100% complete remission rates and excellent CAR engraftment/expansion. Additional patients, updated data and longer follow up will be presented.

Keyword(s): CAR-T, Indolent non-Hodgkin's lymphoma

Presentation during EHA2021: All e-poster presentations will be made available as of Friday, June 11, 2021 (09:00 CEST) and will be accessible for on-demand viewing until August 15, 2021 on the Virtual Congress platform.

Abstract: EP788

Type: E-Poster Presentation

Session title: Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Background
We have previously described AUTO1 (CAT19), a CD19 CAR with a fast off-rate CD19 binding domain, designed to reduce CAR T-cell 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 fucntion of the receptor, with low levels of CRS/ICANS and long-term engraftment of CAR T-cells observed in both patient groups. Recently, CAR therapy has been explored in indolent lymphomas such as follicluar (FL) and mantle cell lymphoma (MCL), but a high incidence of toxicity inluding Grade 3-4 ICANS has been reported.

Aims
We have initiated testing of AUTO1 (CAT19) in the setting of indolent B-cell lymphoma (NCT02935257).

Methods
Manufacturing: CAR T-cell products were generated using a semi-automated closed process from non-mobilised leucapheresate. Study design: subjects>/=16y underwent lymhpodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by a single CAR T-cell infusion of 200 x10^6 CD19 CAR T-cells. Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months.

Results
As of 18 February 2021, we recruited 10 patients of median age 57 years (range 39-68y), 7 with FL and 3 with MCL. Patients had received a median of 3 prior lines (range 2-5) and all patients had stage III/IV disease at screening. Apheresis and product manufacture was successful in all 10 patients and 9 patients were infused: 7 with FL and 2 with MCL. Grade1 CRS was reported in 4/9 and Grade 2 CRS in 1/9. 1/9 developed MAS which resolved with anakinra/dexamethasone. No ICANS was observed on study. Excellent CAR engraftment was observed and 9/9 patients were in CMR by 18FDG PET-CT post-treatment. At a median of 3.1 months (range 1-5.6m), 8/9 patients are in ongoing remission. One patient died in CMR at month 5.6 of COVID-19.

Conclusion
AUTO1 (CAT19) has a tolerable safety profile in adult patients with r/r low grade B-cell lymphoma despite high disease burden. Early data shows 100% complete remission rates and excellent CAR engraftment/expansion. Additional patients, updated data and longer follow up will be presented.

Keyword(s): CAR-T, Indolent non-Hodgkin's lymphoma

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