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
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.
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.
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%).
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.
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