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3318 Safety, Efficiency and Long-Term Follow-up of AUTO1, a Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia and Other B-Cell Malignancies

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological therapies, CLL, Lymphomas, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, indolent lymphoma, aggressive lymphoma, Therapies, Lymphoid Malignancies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Claire Roddie1*, Juliana Dias Alves Pinto, PhD2*, Maeve A O'Reilly1, Marina Mitsikakou, BSc; MSc3*, Eftychia Charalambous, BSc(Hons); MSc4*, Louisa Green, BSc3*, Mhairi Vaughan, BSc; MSc3*, Giulia Agliardi, BSc(Hons); PhD4*, John Garcia, BSc(Hons); PhD4*, Evie Lewin, BSc(Hons); MSc4*, Mark W. Lowdell, PhD, FRCPath, FRSB5*, Maria A V Marzolini6*, Leigh Wood, BA7*, Helen Holmes, BSc(Hons); MSc8*, Yenting Ngai, PhD9*, Bilyana Popova, MSc10*, William Wilson11*, Sangeetha Kunaseelan12*, Victoria Spanswick13*, Helen Lowe3*, Leah Ensell14*, John A. Hartley, PhD13*, Simon Morley15*, David C. Linch16*, Adrian Bloor, PhD FRCP FRCPath17*, David A. Irvine, BSc, MBBChir, MRCP, FRCPath, PhD18, Martin Pule, MD, PhD4* and Karl S Peggs, MD, PhD19*

1University College London Hospital NHS Foundation Trust, London, United Kingdom
2UCL Cancer INstitute, london, United Kingdom
3UCL Cancer Institute, University College London, London, United Kingdom
4Cancer Institute, University College London, London, United Kingdom
5Cancer Institute, University College London, London, GBR
6Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
7University College London Hospital, London, United Kingdom
8CRUK UCL Cancer Trials Centre, University College London, London, United Kingdom
9UCL CRUK Cancer Trials Centre, University College London, London, United Kingdom
10CRUK UCL Cancer Trials Centre, UCL, London, United Kingdom
11UCL Cancer Trials Centre, London, United Kingdom
12CRUK Cancer Trials Centre, University College London, London, United Kingdom
13UCL Cancer Institute, London, United Kingdom
14UCL ECMC GCLP Laboratory, University College London, London, United Kingdom
15University College London Hospitals NHS Trust, London, United Kingdom
16University College London, London, United Kingdom
17Haematology, The Christie Hospital NHS Foundation Trust, Manchester, United Kingdom
18Queen Elizabeth University Hospital, Glasgow, Scotland, GBR
19University College London Cancer Institute, London, United Kingdom

INTRODUCTION:

AUTO1 is a fast off-rate CD19 binding domain CAR, designed to reduce immune toxicity and improve engraftment. Its clinical activity has been tested in r/r paediatric and adult B-ALL (Ghorashian S et al., Nat Med 2019; Roddie C et al., JCO 2021) and now in adult B-NHL and CLL/SLL (NCT02935257). Here we present data from adult B-NHL and CLL cohorts treated with AUTO1, and report on long-term follow-up of adult B-ALL patients post-AUTO1.

METHODS:

Manufacturing: AUTO1 products were generated using a closed process from non-mobilised patient leukapheresis.

Study design: Subjects ≥ 16y received fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) conditioning. DLBCL patients additionally received pembrolizumab (200mg) on day -1. In B-ALL, patients received split dose AUTO1 (day 0: ≥20% Bone Marrow (BM) blasts, AUTO1 dose=10 x106; <20% BM blasts, AUTO1 dose=100 x106. At day+9: if no grade 3-5 CRS/ICANS, dose 2 is administered to a total AUTO1 dose of 410 x106. Split dosing is employed in the CLL cohort (day 0 AUTO1 dose= 30 x106; day 9 AUTO1 dose= 200 x106). B-NHL patients receive a single AUTO1 dose of 200 x106. Study endpoints include manufacture feasibility, grade 3-5 toxicity and remission rates at 1 and 3 months.

RESULTS:

NHL/CLL cohort: as of 27th July 2022, 28 patients were enrolled: 9 with Follicular Lymphoma (FL), 4 with Mantle Cell Lymphoma (MCL), 8 with DLBCL and 7 with CLL. Apheresis/ manufacture was successful in 26 (1x pending; 1x not harvested due to intracerebral haemorrhage). Median age was 61 years (range 39-79), and patients received a median of 3 prior treatment lines (range 2-8). To date, 23 patients have been infused: 7 FL, 3 MCL, 8 DLBCL and 5 CLL. 2 patients died pre-infusion (1x MCL, COVID-19; 1x CLL, intracerebral haemorrhage).

Grade 1 CRS was reported in 7/23 and Grade 2 CRS in 7/23 patients. No ICANS was observed. AUTO1 engraftment was demonstrated in 18/18 patients evaluated by qPCR with ongoing persistence in 17/18 patients at last follow-up.

The ORR at month 1 in the FL, MCL and DLBCL cohorts was 7/7 (100%), 3/3 (100%) and 7/8 (88%) respectively, and ongoing responses at last follow-up (FU) were observed in 5/7 FL (FU range, 5-21 months), 2/3 MCL (range, 12-18 months), and 7/8 DLBCL (range, 1-12 months). 2 patients died in remission from COVID-19.

In the CLL cohort, 4/5 patients achieved flow negative remission in the bone marrow with ongoing response in all 4 at last FU.

B-ALL cohort: of the 20 B-ALL patients treated previously, 8/20 (40%) are in ongoing CR at a median FU of 35 months (IQR 24-36) post-AUTO1, with ongoing B-cell aplasia in 7/8 (89%).

CONCLUSIONS:

AUTO1 has a tolerable safety profile in patients with r/r B-cell cancers despite high disease burden. In the B-ALL cohort, long-term follow-up indicates that 40% of patients continue in remission post-AUTO1. In both indolent and aggressive NHL and in CLL, AUTO1 shows excellent ORR and CAR engraftment/persistence. Additional patients, updated data and longer follow up will be presented.

Disclosures: Roddie: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. O'Reilly: Kite Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel to educational meetings, Speakers Bureau; Novartis: Honoraria, Other: travel to educational meetings. Agliardi: Autolus: Ended employment in the past 24 months. Lowdell: Sartorius GmbH: Consultancy; Avectas Ltd: Consultancy. Hartley: ADC therapeutics: Consultancy. Linch: Autolus: Consultancy. Bloor: Janssen: Consultancy, Honoraria, Other: Grant and personal fees, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Grant and personal fees, Speakers Bureau. Pule: Autolus Ltd: Current Employment, Current equity holder in publicly-traded company. Peggs: Achilles Therapeutics: Current Employment.

*signifies non-member of ASH