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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 x10^6 CD19 CAR T-cells at day 0 and day 9 is employed in the CLL cohort. A single dose of 200 x10^6 CD19 CAR T-cells is delivered to patients with B-NHL. Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months. RESULTS As of 17th May 2021, we recruited 13 patients: 7 with FL, 4 with MCL, 1 DLBCL and 1 CLL. Apheresis and product manufacture was successful in all 13 patients and 9 patients were infused: 7 with FL and 2 with MCL. Three patients (1 DLBCL, 1 CLL and 1 MCL) were pending infusion at time of data cut-off and 1 patient (MCL) died due to Covid-19 prior to infusion. Patients treated with AUTO1 had a median age of 56 years (range 39-68y), had received a median of 3 prior lines of treatment (range 2-5) and all patients had stage IV disease at screening. Grade 1 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 6.1 months (range 4.0-8.1m), 8/9 patients were disease free at last follow-up. One patient died in CMR at month 5.6 of COVID-19. CONCLUSION AUTO1 has a tolerable safety profile in adult patients with r/r B-NHL despite high disease burden. Early data shows 100% complete remission rates and excellent CAR engraftment/expansion. Additional MCL, CLL and DLBCL patients, updated data and longer follow up will be presented. Disclosures Roddie: Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy; Gilead: Consultancy, Speakers Bureau. Hartley: Astra Zeneca: Ended employment in the past 24 months; ADC Therapeutics: Consultancy, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Farzaneh: Autolus: Consultancy, Current equity holder in publicly-traded company. Lowdell: Autolus: Consultancy, Current equity holder in publicly-traded company. Linch: Autolus: Consultancy, Current equity holder in publicly-traded company. Pule: Autolus: Current Employment, Current equity holder in publicly-traded company. Peggs: Autolus: Consultancy, Current equity holder in publicly-traded company.

Background: It has been suggested that dietary freedom in functional insulin therapy may be detrimental to glycemic control in type 1 diabetes. This study evaluates the effect of carbohydrate intake on glycemic control and postprandial blood glucose concentrations. Methods: Insulin pump data from 148 adults with type 1 diabetes, trained in functional insulin therapy, using pumps for ≥6 months, with ≥2 weeks of consecutive downloaded data, ≥80% use of a bolus calculator, ≥3 capillary blood glucose tests/day, and a concurrent HbA1C, were analyzed. More detailed periprandial data (pre- and postmeal glucose, carbohydrate intake, insulin bolus) were collected from a subset of 105 downloads (3495 meals). Results: Mean (± SD) age of contributors was 43 ± 13 years, HbA1C 7.84% ± 0.93 (62.19 mmol/mol); daily carbohydrate intake 166 ± 71 g. HbA1C reduced with increased meals/day ( r = –.370, P < .0005) and increased with mean carbohydrate content/meal ( r = .198, P = .043). However, total daily carbohydrate intake had a weak but significant negative association with HbA1C ( r = –.181, P = .027). There was no association between standard deviation of carbohydrate intake and HbA1C ( r = .021, P = .802) or between meal carbohydrate content and postprandial change in blood glucose ( r = –.004, P = .939) for meals with early postprandial (1-3 hours; n = 390) readings. There was a weak positive correlation ( r = .184, P = .008) between meal carbohydrate content and late (4-7 hours; n = 390) postprandial readings. Discussion: With appropriate training, patients using insulin pumps can accommodate a flexible diet with variable carbohydrate intake, without detriment to glycemic control. However, large carbohydrate meals may contribute to poorer outcomes, through impact on late postprandial glycemia.

OBJECTIVE To evaluate the effect of continuous glucose monitoring (CGM) on the frequency of severe hypoglycemia (SH) in patients with established hypoglycemia unawareness. RESEARCH DESIGN AND METHODS We conducted a retrospective audit of 35 patients with type 1 diabetes and problematic hypoglycemia unawareness, despite optimized medical therapy (continuous subcutaneous insulin infusion/multiple daily insulin injections), who used CGM for >1 year. RESULTS Over a 1-year follow-up period, the median rates of SH were reduced from 4.0 (interquartile range [IQR] 0.75–7.25) episodes/patient-year to 0.0 (0.0–1.25) episodes/patient-year (P < 0.001), and the mean (±SD) rates were reduced from 8.1 ± 13 to 0.6 ± 1.2 episodes/year (P = 0.005). HbA1c was reduced from 8.1 ± 1.2% to 7.6 ± 1.0% over the year (P = 0.005). The mean Gold score, measured in 19 patients, did not change: 5.1 ± 1.5 vs. 5.2 ± 1.9 (P = 0.67). CONCLUSIONS In a specialist experienced insulin pump center, in carefully selected patients, CGM reduced SH while improving HbA1c but failed to restore hypoglycemia awareness.