Novartis Pharmaceuticals Corporation Research Articles

746-P: The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES) : Final 24-Month Primary Endpoint Analysis

TROPHIES was a 24-month, prospective, non-comparative, observational study in adult patients with T2D initiating their first injectable glucose-lowering treatment with once-weekly dulaglutide (DU; N=1,014) or once-daily liraglutide (LIRA; N=991) in France, Germany, and Italy. Primary objective: to assess the time patients remained on their first GLP-1 RA without a significant treatment change due to treatment- or diabetes-related factors. Kaplan-Meier (KM) probability (95% CI) of no significant treatment change at 24 months was 0.71 (0.68-0.74) and 0.53 (0.49-0.56) in the DU and LIRA cohorts, respectively (Figure) . Two-hundred and eighty-six (28.2%) and 448 (45.2%) patients receiving DU and LIRA, respectively, had a significant treatment change. The main driver of treatment change in the DU and LIRA cohorts was intensification with an add-on therapy (insulin or OAD) and intensification with dose increase of GLP-1 RA, respectively. KM probability (95% CI) of GLP-1 RA persistence at 24 months was high in both cohorts: DU 0.82 (0.80-0.85) ; LIRA 0.75 (0.72-0.78) . In summary, the probabilities of no significant treatment change over 24 months were estimated as higher in the DU cohort than in the LIRA cohort in this non-comparative analysis, with good persistence in both cohorts. Disclosure F. Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. Consultant; Lilly Diabetes, Sanofi. Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. B. Guerci: Advisory Panel; Amgen Inc., Medtronic. Board Member; Abbott Diagnostics, AstraZeneca, Bayer AG, Eli Lilly and Company, Novartis Pharmaceuticals Corporation. Consultant; Boehringer Ingelheim International GmbH, Intercept Pharmaceuticals, Inc., Novo Nordisk. L. Garcia-Perez: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M. Fuechtenbusch: Advisory Panel; Berlin-Chemie AG. Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp. Speaker's Bureau; AstraZeneca, Novo Nordisk. J. Lebrec: Consultant; Eli Lilly and Company. M. Orsini Federici: Employee; Eli Lilly and Company. A. Dib: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. E. Heitmann: None. M. Yu: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. K. Boye: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

846-P: Advancing Therapy in Basal Insulin–Treated Type 2 Diabetes: Exploratory Analysis of the SoliMix Trial by Baseline Age, Diabetes Duration, and Renal Function

Introduction: SoliMix (EudraCT: 2017-003370-13) found better HbA1c, weight benefit, and lower hypoglycemia risk with iGlarLixi vs. premix BIAsp 30 in people with type 2 diabetes (T2D) advancing from basal insulin (BI) + oral antihyperglycemic drugs (OADs) . Methods: Adults with T2D and HbA1c 7.5-10.0 % on BI + 1-2 OADs were randomized to once-daily iGlarLixi or twice-daily BIAsp 30 for 26 weeks. Primary outcomes were non-inferiority in HbA1c change or superiority in body weight change from baseline to Week 26. SoliMix endpoints were assessed here by baseline age (<65, ≥65 years) , T2D duration (<10, ≥years) , and renal function (eGFR ≥90, ≥60-<90, and <60 mL/min/1.73 m2) . Results: No differences in treatment effect were observed across subgroups for HbA1c or body weight changes (heterogeneity p>0.05; Table) ; both primary objectives were met in the age, T2D duration, and the eGFR ≥60-<90 mL/min/1.73 m2 subgroups. Baseline subgroup had no effect on the lesser insulin dose increments seen in SoliMix with iGlarLixi vs. BIAsp 30 (p>0.80) . The advantage of iGlarLixi over BIAsp 30 for Level 2 hypoglycemia was found in all subgroups with no difference in treatment effect (p>0.10) . Conclusions: The primary findings for iGlarLixi vs. BIAsp 30 were unaffected by baseline age, T2D duration, or renal function. Disclosure P.Home: Advisory Panel; Kriya Therapeutics, Consultant; Mundipharma, Sanofi, Other Relationship; AstraZeneca, Sanofi, Research Support; Gan & Lee Pharmaceuticals, Sanofi, Speaker's Bureau; Gan & Lee Pharmaceuticals, Medscape. J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. M.Blüher: Consultant; AstraZeneca, Lilly, Novo Nordisk A/S, Pfizer Inc., Sanofi, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG. K.Djaballah: Employee; Sanofi. K.Pegelow: Employee; Sanofi-Aventis Deutschland GmbH. L.Melas-melt: None. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. Funding Sanofi

53-OR: Diabetes Stigma and Clinical Outcomes in Adolescents and Young Adults: The SEARCH for Diabetes in Youth Study

We examined the association between diabetes stigma and glycemic control, treatment regimen, and acute and chronic complications in adolescents and young adults (AYAs) with type 1 (T1D) and type 2 diabetes (T2D) in the SEARCH for Diabetes in Youth Study, 2016-2019. A 5-question survey assessed frequency of perceived stigma experience, from which we created a total stigma score. We used multivariable linear modeling, stratified by T1D and T2D, to examine the association of diabetes stigma with clinical factors, adjusting for sociodemographic, clinic site, duration of diabetes, health insurance type, treatment regimen, and HbA1c. Of 16respondents, 78% had T1D, 56% were female, and 48% were non-Hispanic White. Mean (SD) age at study visit was 21.7 (5.1) years (range - 24.9 years) . Mean (SD) HbA1c was 9.2% (2.3) . Higher stigma scores were associated with female sex and higher HbA1c (both p <0.01, table) . No statistically significant association between stigma score and insulin pump or continuous glucose monitor use was observed. In participants with T2D, higher stigma scores were associated with insulin use (p = 0.04) . Independent of HbA1c, higher stigma scores were associated with acute complications for AYAs with T1D and chronic complications for AYAs with T1D and T2D (table) . Diabetes stigma in AYAs is associated with worse diabetes outcomes and therefore is important to address in diabetes care. Disclosure K.B.Eitel: None. E.T.Jensen: Consultant; Regeneron Pharmaceuticals Inc. A.D.Liese: None. S.M.Marcovina: None. E.J.Mayer-davis: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. C.Pihoker: None. A.J.Roberts: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. R.A.Bell: None. A.Bellatorre: None. C.E.Barrett: None. A.Cristello: None. D.Dabelea: None. L.M.Dolan: None. Funding The SEARCH for Diabetes in Youth Cohort Study (1R01DK127208-01, 1UC4DK108173) is funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases and supported by the Centers for Disease Control and Prevention.

845-P: Advancing Therapy in Basal Insulin–Treated Type 2 Diabetes: Exploratory Analysis of the SoliMix Trial by Baseline HbA1c, Insulin Dose, and BMI

Introduction: SoliMix (EudraCT: 2017-003370-13) found better HbA1c, weight benefit, and lower hypoglycemia risk requiring less insulin with once-daily iGlarLixi vs. twice-daily premix BIAsp 30 in people with type 2 diabetes (T2D) advancing from basal insulin (BI) and oral antihyperglycemic drugs (OADs) . Methods: Adults with T2D and HbA1c 7.5-% on BI + 1-2 OADs were randomized to iGlarLixi or BIAsp 30 for 26 weeks. Primary outcomes were non-inferiority in HbA1c change or superiority in body weight change with iGlarLixi vs. BIAsp 30. This post hoc analysis assessed SoliMix endpoints by baseline HbA1c (7.5-8, >8-9, >9-%) , insulin dose (<30, ≥30 U/day) , and BMI (<25, ≥25-<30, ≥30-<35, ≥35 kg/m2) . Results: No differences in treatment effect were seen across subgroups for change in HbA1c or BMI (heterogeneity p>0.10; Table) ; both primary objectives were met in the HbA1c >8-≤9 %, BMI ≥25-<30 kg/m2, and insulin dose subgroups. No differences in treatment effect were seen across subgroups for the lesser insulin dose increments with iGlarLixi vs. BIAsp 30 (p>0.10) . Level 2 hypoglycemia incidence and rates were unaffected by baseline HbA1c and BMI (p>0.10) , but p<0.for events by insulin dose. Conclusions: Primary SoliMix findings for iGlarLixi vs. BIAsp 30 were consistent across baseline HbA1c and BMI subgroups but inconsistent for baseline insulin dose. Disclosure P.Home: Advisory Panel; Kriya Therapeutics, Consultant; Mundipharma, Sanofi, Other Relationship; AstraZeneca, Sanofi, Research Support; Gan & Lee Pharmaceuticals, Sanofi, Speaker's Bureau; Gan & Lee Pharmaceuticals, Medscape. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. J.Rosenstock: Consultant; AstraZeneca, Other Relationship; Applied Therapeutics, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Hanmi Pharm. Co., Ltd., Intarcia Therapeutics, Inc., Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Research Support; Genentech, Inc., Merck & Co., Inc., Metacrine, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., vTv Therapeutics. M.Blüher: Consultant; AstraZeneca, Lilly, Novo Nordisk A/S, Pfizer Inc., Sanofi, Speaker's Bureau; Bayer AG, Boehringer Ingelheim International GmbH, Novartis AG. K.Pegelow: Employee; Sanofi-Aventis Deutschland GmbH. L.Melas-melt: None. K.Djaballah: Employee; Sanofi. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. Funding Sanofi

1224-P: Multidimensional Characterization of Prediabetes in the Project Baseline Health Study

Prediabetes is a recognized entity but has been incompletely characterized in a contemporary context. We sought to characterize participants with prediabetes with extensive multi-dimensional clinical and laboratory data and to identify predictors of progression to diabetes. The Project Baseline Health Study (PBHS) is a multi-site prospective U.S. cohort study of 2502 adults with deep clinical phenotyping at enrollment. At enrollment and follow-up, participants were classified by diabetes status (diabetes [DM], prediabetes [preDM], or no diabetes [noDM]) based on glucose, A1c, medications, and self-reported medical history. Principal component analysis (PCA) was performed on 1clinical, survey, and lab variables to create orthogonal factors composed of correlated variables, which were compared between groups using linear models. Logistic regression was used to identify factors associated with progression from preDM to DM. At enrollment, 16participants had noDM; 544 had preDM; and 352 had DM. Over up to 4 years of follow-up, 52 participants with preDM developed DM. PCA identified 33 factors composed of clusters of clinical variables; 24 factors differed significantly by diabetes status: 6 factors significantly differed between noDM and both preDM and DM after adjustment for multiple comparisons, including factors with variables of glucose measures, anthropometry and physical function (q= 1.3 × 10−21) , red blood cell indices (q= 8.3 × 10−10) , lung function (q= 2.0 × 10−6) , cardiac function (q= 0.001) , and risk of chronic disease. Five factors were significantly associated with progression to DM, including factors of anthropometry and physical function [OR (95% CI) 0.6 (0.5,0.9) ], hematologic measures, and cardiac function. Conclusions: PBHS participants with preDM demonstrated pathophysiologic changes in cardiac, pulmonary, and hematology measures and declines in physical function that precede DM and could be markers of higher risk of progression to DM and complications. Disclosure R.Chatterjee montgomery: Research Support; Bristol-Myers Squibb Company, Epigenomics AG. L.C.Kwee: None. N.Pagidipati: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, ESPERION Therapeutics, Inc., Consultant; Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eggland's Best, Eli Lilly and Company, Novartis AG, Novo Nordisk, Sanofi, Verily Life Sciences. A.F.Hernandez: Consultant; Merck & Co., Inc., Novo Nordisk, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH. F.Rodriguez: Advisory Panel; Amgen Inc., Consultant; HealthPals, Novartis Pharmaceuticals Corporation, Novo Nordisk, Stock/Shareholder; Carta Healthcare, Inc. K.W.Mahaffey: Consultant; Novo Nordisk. L.Palaniappan: Consultant; Amgen Inc. S.H.Shah: Research Support; Verily Life Sciences. Funding The Baseline Health Study and this analysis were funded by Verily Life Sciences, San Francisco, California.

1-LB: Trends in Incidence and Age at Diagnosis of Youth-Onset Type 2 Diabetes, 2002–2018—The SEARCH for Diabetes in Youth Study

The SEARCH study ascertained individuals with type 2 diabetes (T2D) diagnosed at <20 years of age at 5 study centers in the US from 2002 to 2018 and calculated annual incidence as number of cases divided by the population <20 years in the catchment area (∼5 million annually based on US Census or health-plan member counts) . We estimated incidence trends using a generalized autoregressive (2-year) moving average model. From annual incidence, we calculated peak age at T2D diagnosis overall population and within period, sex, race and ethnicity strata. Incidence increased from 2002-2009 to 2010-2018 (p<0.0001) ; however, the peak age at diagnosis did not change (16 years; Figure) . Across all years, the peak age at diagnosis was similar between females (16 years [95% CI 15-18]) and males (16 years [16-18]) . The peak age at diagnosis was younger for non-Hispanic Black youth (NHB; 13 years) , while similar for American Indian (AI) , Asian and Pacific Islander (API) , Hispanic (HISP) , and non-Hispanic White (NHW) youth (16 years; Figure) . These data indicate continued increases in T2D incidence across ages associated with the pubertal transition, with a rapid decline following the incidence peak. They also highlight an earlier T2D onset among NHB youth. These results highlight the need for pre-pubertal or early pubertal intervention to mitigate risk of youth-onset T2D. Disclosure K. A. Sauder: None. A. Bellatorre: None. J. M. Lawrence: None. J. Divers: None. E. T. Jensen: Consultant; Regeneron Pharmaceuticals Inc. L. E. Wagenknecht: None. A. D. Liese: None. D. Dabelea: None. S. M. Marcovina: None. C. Pihoker: None. K. Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. A. S. Shah: None. L. M. Dolan: None. Funding Centers for Disease Control and Prevention and National Institutes of Health

738-P: The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES) : Final 24-Month Patient-Reported Outcomes

Data on patient-reported outcome (PRO) measures in people living with T2D who initiate injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) medication in routine clinical practice are limited. Here we present final PRO data from the TROPHIES 24-month, prospective, non-comparative, observational study of adult patients with T2D in France, Germany and Italy who started their first injectable GLP-1 RA with either once-weekly dulaglutide (DU) or once-daily liraglutide (LIRA) . Patients’ scores on PRO questionnaires were assessed every 6 months. We present scores at 24 months compared with baseline values before starting DU or LIRA treatment. For each PRO measure, higher scores reflect better outcomes. Baseline characteristics (previously published) for patients prescribed DU (N=1,014) or LIRA (N=991) were similar between groups. Mean changes from baseline to 24 months in PRO scores indicate improvements in health outcomes in patients initiating DU or LIRA (Table) . In summary, among those patients still evaluable at 24 months we observed improvements in PRO scores from baseline in both groups, but with a more pronounced trend of improvement in the DU cohort for EQ-5D-5L VAS, IW-SP, DTSQs total, and DPM life and work productivity scores. Disclosure M.Fuechtenbusch: Advisory Panel; Berlin-Chemie AG, Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Speaker's Bureau; AstraZeneca, Novo Nordisk. K.Boye: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. B.Guerci: Advisory Panel; Amgen Inc., Medtronic, Board Member; Abbott Diagnostics, AstraZeneca, Bayer AG, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Consultant; Boehringer Ingelheim International GmbH, Intercept Pharmaceuticals, Inc., Novo Nordisk. F.Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Consultant; Lilly Diabetes, Sanofi, Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. L.Garcia-perez: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. E.Heitmann: None. J.Lebrec: Consultant; Eli Lilly and Company. A.Barrett: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Dib: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. M.Orsini federici: Employee; Eli Lilly and Company.

1085-P: Exploring Racial and Ethnic Disparities in Arterial Stiffness in Type 1 Diabetes

We studied arterial stiffness in youth and young adults with T1D and potential longitudinal mediators of racial and ethnic disparities. SEARCH for Diabetes in Youth Study participants (n=2317; 14% Hispanic, 12% non-Hispanic Black, 74% non-Hispanic White) had CV risk factors (body size, lipid profile, blood pressure, A1c, urinary creatinine, pulse) measured 2-6 times from ∼9 months up to ˜years after T1D diagnosis. Arterial stiffness was measured with pulse wave velocity (PWV) at ˜years T1D duration (˜18 years of age) . For each risk factor, we summarized the longitudinal data as mean, max, slope, and area-under-the-curve (AUC) . Using split test/replication datasets, we a) identified the summary statistic for each risk factor most associated with PWV using flipped multivariate general linear models, and b) used the resulting statistics to construct a risk score predicting PWV with a stepwise general linear model. The final score included AUC for BMI, triglycerides and creatinine; heart rate slope; max mean arterial pressure; and age and T1D duration at PWV measurement, explaining 35% of variability in PWV at 18 years. PWV varied by race and ethnicity (Figure - left) . Adjustment for the risk score partially attenuated this disparity (Figure - right) . These data suggest CV risk factors from T1D diagnosis onward are related to racial and ethnic disparities in arterial stiffness, but other factors are likely involved. Disclosure K.A.Sauder: None. S.M.Marcovina: None. E.J.Mayer-davis: None. A.K.Mottl: Advisory Panel; Bayer AG, Board Member; Bayer AG, Research Support; Alexion Pharmaceuticals, Inc., Aurinia, Bayer AG, Boehringer Ingelheim International GmbH, Pfizer Inc. C.Pihoker: None. K.Reynolds: Research Support; Amgen Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. A.S.Shah: None. E.M.Urbina: Advisory Panel; Astellas Pharma Inc. L.E.Wagenknecht: None. S.R.Daniels: None. D.Dabelea: None. D.H.Glueck: None. K.K.Harrall: None. R.Dagostino: Consultant; Aetion, Inc., AstraZeneca, Biogen, Bristol-Myers Squibb Company, Daiichi Sankyo, Merck & Co., Inc. L.M.Dolan: None. A.Lane-cordova: None. A.D.Liese: None. E.Lustigova: None. F.Malik: n/a. Funding National Institutes of Health

736-P: Effect of Semaglutide on Liver Steatosis/Fibrosis Indexes in Patients with Diabetes and Obesity

Aim: To assess the efficacy of Semaglutide on liver steatosis/fibrosis indexes. Methods: Observational, multicenter study. Steatosis/fibrosis were determined by HSI (<30 rule out, >36 steatosis) and FIB-4 (<1.3 rule out, >2.67 fibrosis) . Results: 213 patients (46.9% women) , age 64 (19) years. Variables and 24 wk changes are shown in table 1. 100% of patients had altered steatosis biomarkers (HSI 47.9 (8.2)) , 10.8% fibrosis (FIB-4> 2.76) . A significant reduction in HSI [-2.36 (95%CI 1.83-2.9) p<0.0000] and FIB-4 [-0.075 (95%CI0.015-0.14) p<0.016] were found (Table 1) . There was a correlation between weight loss and HSI, GGT or TyG improvement (figure 1) . Conclusion: Our results show a beneficial effect of Semaglutide on steatosis that goes beyond glucose control, and it is related mainly with weight loss and decline in biomarkers. Disclosure J.Carretero gomez: None. F.Carrasco-sánchez: None. J.Fernandez: Advisory Panel; Boehringer Ingelheim International GmbH, Daiichi Sankyo, Lilly Diabetes, Novartis Pharmaceuticals Corporation, Sanofi Genzyme, Speaker's Bureau; Amgen Inc., Novo Nordisk Foundation. P.Casado: None. P.Diabetes, nutrition and obesity working group of s: n/a. J.Arevalo lorido: None. J.Miramontes gonzález: None. J.Segí-ripoll: None. J.Ena: None.

726-P: The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES) : Final 24-Month Clinical Characteristics and Treatment Pattern Analyses

TROPHIES was a 24-month, prospective, non-comparative, observational study in adult patients with T2D initiating their first injectable glucose-lowering treatment with once-weekly dulaglutide (DU; N=1,014) or once-daily liraglutide (LIRA; N=991) in France, Germany, and Italy. Secondary objectives included assessments of HbA1c, body weight and treatment patterns. Clinical characteristics of the DU and LIRA cohorts at 24 months are described in the Table. Most patients receiving DU (856/1,014) initiated treatment at 1.5 mg/week and, among 286 patients with a significant treatment change, 237 were still receiving 1.5 mg/week. In the LIRA cohort, most patients (809/991) initiated at the starting dose 0.6 mg/day and 45% increased dose to 1.2 mg/day by Day 90; however, 17% of patients were already receiving 1.8 mg/day by Day 90. At the first significant treatment change 285/448 patients in the LIRA cohort were receiving 1.2 mg/day. Insulin was initiated by 79 and 97 patients in the DU and LIRA cohorts, respectively. Both treatments showed clinically meaningful effectiveness on HbA1c and weight, maintained over the 24-month study period. Disclosure B. Guerci: Advisory Panel; Amgen Inc., Medtronic. Board Member; Abbott Diagnostics, AstraZeneca, Bayer AG, Eli Lilly and Company, Novartis Pharmaceuticals Corporation. Consultant; Boehringer Ingelheim International GmbH, Intercept Pharmaceuticals, Inc., Novo Nordisk. F. Giorgino: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. Consultant; Lilly Diabetes, Sanofi. Research Support; Lilly Diabetes, Roche Diabetes Care, Takeda Pharmaceutical Company Limited. K. Boye: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M. Fuechtenbusch: Advisory Panel; Berlin-Chemie AG. Consultant; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp. Speaker's Bureau; AstraZeneca, Novo Nordisk. E. Heitmann: None. J. Lebrec: Consultant; Eli Lilly and Company. A. Dib: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M. Orsini Federici: Employee; Eli Lilly and Company. M. Yu: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. L. Garcia-Perez: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.

OP0023 A RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING SECUKINUMAB 300 MG AND 150 MG AT WEEK 52 IN PATIENTS WITH ANKYLOSING SPONDYLITIS WHO DID NOT ACHIEVE INACTIVE DISEASE DURING AN INITIAL 16 WEEKS OF OPEN-LABEL TREATMENT WITH SECUKINUMAB 150 MG

OP0023 A RANDOMIZED, DOUBLE-BLIND TRIAL COMPARING SECUKINUMAB 300 MG AND 150 MG AT WEEK 52 IN PATIENTS WITH ANKYLOSING SPONDYLITIS WHO DID NOT ACHIEVE INACTIVE DISEASE DURING AN INITIAL 16 WEEKS OF OPEN-LABEL TREATMENT WITH SECUKINUMAB 150 MG

Comparison of early diabetic retinopathy staging in asymptomatic patients between autonomous AI-based screening and human-graded ultra-widefield colour fundus images

Learning ObjectivesUpon completion of this activity, participants will:Compare diabetic retinopathy (DR) severity scores of ophthalmologically asymptomatic people with diabetes between outputs from an artificial intelligence (AI)-based system and human-graded ultra-widefield (UWF) color fundus imaging, according to a clinical study.Compare manual 7F-mask gradings vs UWF full-field gradings and describe the correlation with patient characteristics, according to a clinical study.Describe clinical implications of the comparison between the DR severity scores of ophthalmologically asymptomatic people with diabetes outputs using outputs from an AI-based system and human-graded UWF color fundus imaging, according to a clinical study.Accreditation StatementsIn support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Springer Nature. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at www.medscape.org/journal/eye; (4) view/print certificate.Credit hours1.0Release date:Expiration date:Post-test link:https://www.medscape.org/eye/posttest964708Authors/Editors disclosure informationS.S. has disclosed the following relevant financial relationships: Served as consultant or advisor for Allergan, Inc.; Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Heidelberg Pharma GmbH; Novartis Pharmaceuticals Corporation; Optos; Roche; Served as a speaker or a member of a speakers bureau for Allergan, Inc.; Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos; Roche; Received research funding from Bayer HealthCare Pharmaceuticals; Boehringer Ingelheim Pharmaceuticals, Inc.; Novartis Pharmaceuticals Corporation; Optos; Is employed by or has an executive role as Data Monitoring Chair for Phase 2 study sponsored by Bayer HealthCare Pharmaceuticals; Scientific Committee Member of EyeBio Steering Committee for FOCUS sponsored by Novo Nordisk. Other: Trustee member for Macular Society Scientific/Research Advisory Committee Member for Sight UK, Retina UK, Macular Society.Journal CME author disclosure informationLaurie Barclay has disclosed no relevant financial relationships.

Omalizumab and quality of life in nasal polyps: A post hoc analysis.

Omalizumab and quality of life in nasal polyps: A post hoc analysis.

Clinical Characteristics and Late-Line Treatment Patterns of Patients with Chronic Myeloid Leukemia Who Received 2 Prior Lines of Tyrosine Kinase Inhibitor Therapy in US Community Oncology Practices

BACKGROUND: Current treatment guidelines recommend tyrosine kinase inhibitors (TKIs) as first-line and second-line treatment options for patients with chronic myeloid leukemia (CML). 1,2 However, approximately 20% of CML patients fail to respond to the first- and second-generation TKIs, and evidence-based guidelines for late-line treatment options after failure/intolerance to TKIs are limited. 3,4 Therefore, this study sought to describe the clinical characteristics and real-world treatment patterns of CML patients who received 2 prior lines of TKI therapy.METHODS: A retrospective cohort design was utilized to identify adult CML patients who initiated a new line of therapy (LOT) after 2 prior lines of TKI therapy between 4/2013 and 12/2020 in the Florida Cancer Specialists network's electronic health records (EHR) database. The index LOT date was the start date of a new CML treatment regimen in LOT≥3 after 2 prior lines of TKI therapy. Patients were followed until 1 of the following occurred: death, loss to follow-up (last structured activity in EHR), or end of study period (3/31/2021). Demographic and clinical characteristics were captured during the baseline period starting 3 months prior to the initial CML diagnosis until the index LOT date and included age, gender, race, Eastern Cooperative Oncology Group performance status (ECOG PS) and comorbidity burden. Treatment patterns of all available LOTs from initial CML diagnosis were investigated and the following metrics were captured: regimen details of systemic CML therapies, duration of LOT, treatment-free interval. This study was descriptive in nature and no inferential statistics were computed.RESULTS: A total of 157 patients who initiated a new CML treatment regimen in LOT≥3 after 2 previous lines of TKI therapy were included in this study. The median age of the study sample at initial CML diagnosis was 63.8 years, 57.3% of the sample were male, and 50.3% were White. At index LOT, 46.5% of the sample had an ECOG PS score of 0-1, 5.1% had ECOG PS score of 2-4, and 48.4% had an unknown ECOG PS score. The majority of the sample initiated the index LOT in LOT 3 (n=151; 96.2%) vs in LOT 4 (n=6; 3.8%). The median duration of the index LOT was 6.6 months with median follow-up from index LOT being 23.0 months. After 2 prior lines of TKI therapy, 93.0% of the sample continued on TKIs only, 1.3% initiated a non-TKI CML drug, and 5.7% received a combination of CML drugs. Dasatinib (31.2%) and imatinib (30.6%) were the most commonly used TKIs in the index LOT. There was significant variability in the treatment sequences across LOTs, however, 50.3% of the sample restarted the same TKI in their index LOT which had been used in a prior LOT. A total of 65 patients (41.4%) initiated a new LOT after the index LOT, and the treatment-free interval following the index LOT was 1.8 months, on average.CONCLUSIONS: The majority of the CML patients who received 2 prior lines of TKI therapy continue to cycle through additional LOTs containing TKIs, and half of the patients restart the same TKI used in a prior LOT. The findings of this study highlight the need for better novel therapies that can fill the treatment gap for CML patients who are refractory or intolerant to TKIs. REFERENCES1. Deininger MW, Shah NP, Altman JK, et al. Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(10):1385-1415.2. Hochhaus A, Saussele S, Rosti G, et al. Chronic myeloid leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl 4):iv41-iv51.3. Perrotti D, Jamieson C, Goldman J, et al. Chronic myeloid leukemia: mechanisms of blastic transformation. J Clin Invest. 2010;120(7):2254-2264.4. Cortes J, Lang F. Third-line therapy for chronic myeloid leukemia: current status and future directions. J Hematol Oncol. 2021;14(1):44. DisclosuresPatel: Novartis Pharmaceuticals Corporation: Research Funding. Raju: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Coutinho: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Maegawa: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Lunacsek: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Deyoung: Xcenda LLC: Current Employment, Other: Xcenda LLC received research funding from Novartis Pharmaceuticals Corporation. Iorga: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Cao: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company.

Frequency of Vaso-Occlusive Crises Is Associated with Health-Related Quality of Life in Pediatric Patients with Sickle Cell Disease: US Cross-Sectional Surveys of Adolescents and Caregivers

▪Introduction: Pediatric patients with sickle cell disease (SCD) experience considerable disease-related burden. SCD-related morbidity is characterized by vaso-occlusive crises (VOCs), which are acutely painful events that may cause chronic and potentially life-threatening complications, contributing to the early mortality associated with SCD. Two cross-sectional observational surveys were fielded to evaluate the relationship between VOC frequency and health-related quality of life (HRQoL) in pediatric patients with SCD in the United States (US).Methods: Surveys were administered in 2 populations: adolescents with SCD ages 12-17 years (n=247) and caregivers (n=167) of children with SCD ages 2 months-11 years in the US. Adolescent participants first provided assent to participate, and their guardians provided permission. Adolescents then completed an online survey that included the Child Health Questionnaire-Child Form 45 (CHQ-CF45) and the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) pain and sleep impact domains. After providing informed consent, caregivers completed an online survey assessing the HRQoL of their child with SCD; survey content was tailored to the age of their child. Caregivers of children ages 5-11 completed the CHQ-Parent Form 50 (CHQ-PF50) and the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference and sleep disturbance short forms (8a and 4a, respectively). Caregivers of children <5 completed the Infant/Toddler Quality of Life Questionnaire-Short Form 47 (ITQOL-SF47). Children were stratified according to the number of VOCs they experienced in the past 12 months (0-2 VOCs; ≥3 VOCs), and a series of general linear models were conducted to examine the relationship between VOC frequency and HRQoL domain scores, with children's age included as covariate. Statistical significance was evaluated using a significance level of 0.05; p-values were also compared to a Benjamini-Hochberg adjusted critical value.Results: In adolescents ages 12-17, higher frequencies of VOCs were associated with lower HRQoL: adolescents with more frequent VOCs reported greater impacts than adolescents with less frequent VOCs across all domains of HRQoL measured by the CHQ-CF45, including general health, physical functioning, role/social limitations, mental health, and family activities (p<0.05 for all) (Table 1). Pain and sleep (ASCQ-Me domains) were also associated with VOC frequency: greater impacts were observed among adolescents with more frequent VOCs (p<0.001 for both). Similar to adolescents, children < 12 who experienced more frequent VOCs exhibited lower HRQoL as reported by caregivers on most CHQ-PF50 and ITQOL-SF47 domains except those related to behavior and the ITQOL-SF47 change in health domain (Table 2). Children with more frequent VOCs also experienced greater pain interference and sleep disturbance than those with less frequent VOCs (p<0.01 for both PROMIS domains; Table 2). Among caregivers of children ages 5-11, those whose children experienced more frequent VOCs reported greater impacts on CHQ-PF50 parental time/emotions and family activity domains than those whose children experienced less frequent VOCs (p<0.01 for all; Table 2). Caregivers of children ages 2 months-4 years also reported a similar association between VOC frequency and the ITQOL-SF47 parental time domain (p<0.01; Table 2). ITQOL-SF47 parental emotional impact scores also differed when compared to a significance level of 0.05, but were not statistically different after adjusting for multiple comparisons.Conclusions: Via both self- and caregiver-reports, these surveys demonstrated significant detrimental impact of VOCs on pediatric patients with SCD. Decrements were observed across various domains of HRQoL, including general health, physical functioning, pain, sleep, role/social limitations, and mental health. VOC frequency negatively impacted family activities and caregiver time and emotions, confirming anecdotal evidence that the effects of VOCs extend beyond the child to the caregiver. Given the cross-sectional study design, these analyses did not establish a temporal or causal relationship between VOCs and HRQoL; however, it is plausible that treatments aimed at reducing the frequency of VOCs may alleviate some of the burden experienced by pediatric patients with SCD and their families. [Display omitted] DisclosuresCampbell: Novartis Pharmaceuticals Corporation: Consultancy, Research Funding. Rizio: Novartis Pharmaceuticals Corporation: Other: Avery Rizio is employed by QualityMetric Incorporated, LLC, which received funding from Novartis to conduct this research. McCausland: Novartis Pharmaceuticals Corporation: Other: Kristen McCausland is an employee of QualityMetric Incorporated, LLC, which received funding from Novartis to conduct this research. Iorga: Novartis Pharmaceuticals Corporation: Current Employment, Current equity holder in publicly-traded company. Yen: Novartis Pharmaceuticals: Current Employment; Merck & Co., Inc.: Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Paulose: Novartis Pharmaceuticals Corporation: Current Employment. Lee: Novartis Pharmaceuticals Corporation: Current Employment.

Tisagenlecleucel Leukapheresis and Manufacturing Outcomes in Patients Less Than 3 Years of Age with Relapsed/Refractory Acute Lymphoblastic Leukemia

Background: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR)-T cell therapy approved for patients (pts) ≤25 years of age with B-cell acute lymphoblastic leukemia (B-ALL) that is refractory or in second or later relapse. Pts <3 years of age were excluded from tisagenlecleucel clinical trials in relapsed/refractory (r/r) ALL (NCT02435849 [ELIANA]; NCT02228096 [ENSIGN]). We present leukapheresis and tisagenlecleucel manufacturing outcomes in pts <3 years old with r/r B-ALL in the US commercial setting since regulatory approval.Methods: Qualified pts were <3 years of age at time of request for commercial tisagenlecleucel, with manufacturing data after August 30, 2017 (date of first FDA approval of tisagenlecleucel). Only pts whose tisagenlecleucel was manufactured and administered in the US were included; tisagenlecleucel was manufactured at Morris Plains, NJ, USA. Pt leukapheresis and manufacturing outcome data are presented for all pts and stratified by weight (<10 kg and ≥10 kg) and age (<1 year old and 1-3 years old). These data provide an extended analysis (cut-off March 31, 2021) from the previous report (Eldjerou, 2019).Results: Among 65 pts, the median age was 15.6 months (range, 3.6-36); median body weight was 10.4 kg (range, 6-20) at leukapheresis; 105 leukaphereses were performed in 65 pts (49 <10 kg and 56 ≥10 kg). A median of 1 leukapheresis day was required to meet adequate cell counts (range, 1-4 <10 kg and 1-6 ≥10 kg). The median total blood volume reported in 53/65 pts was 3.5 L (range, 1.3-14.3). The acceptance criteria for tisagenlecleucel manufacture (total nucleated cells: ≥2.0 × 10 9, CD3+ count: ≥1.0 × 10 9, CD3%: ≥3%) were met in 59/66 (26 <10 kg and 33 ≥10 kg) leukapheresis materials; 7/66 did not meet acceptance criteria but proceeded to manufacturing. Following leukapheresis, median percent cell populations were: T cells 55.1% (58% <10 kg and 54.8% ≥10 kg), B-cells 16.9% (20.3% <10 kg and 14.6% ≥10 kg), natural killer cells 4% (3.8% <10 kg and 4.7% ≥10 kg), and monocytes 3.9% (2.6% <10 kg and 4.9% ≥10 kg).Manufacturing success is the formulation of a final product within approved specifications. Out of 66 manufacturing batches (23 batches <1 year old and 43 batches 1-3 years old; 29 batches <10 kg and 37 batches ≥10 kg), 55 (83.3%) were successful. Of the 59 manufacturing batches that met acceptance criteria, 50 were within specification, 2 were terminated, and 7 were out-of-specification due to cell viability (n=4), CAR+% expression (n=2), or another reason (n=1). One pt who experienced manufacturing failure was remanufactured successfully with a second attempt. Of the 7 batches that did not meet the acceptance criteria, 5 were within specifications and 2 were terminated. The median manufactured cell dose was 2.3x10 6 CAR+ viable T cells/kg [range, 0.23-4.6x10 6 (2.5x10 6 <10 kg and 2.1x10 6 ≥10 kg)], median percent cell viability was 90.6% [range, 66.7%-98.3% (91.9% <10 kg and 90% ≥10 kg)], median CAR+ percent expression was 12.0% [range, 2.1%-37.2% (12.2% <10 kg and 11.8% ≥10 kg)]. From 2017 to 2021, the frequency of CD3+ cells present in the leukapheresis material was greatest in 2021 (Figure, left panel). The percentage of in-specification products was 69%-83% in 2017 to 2019 and increased to 89% and 100% in 2020 and 2021, respectively. Additionally, the number of terminations decreased over time (Figure, right panel).Measures for successful leukapheresis in low-weight infant/toddler pts include verification of absolute lymphocyte and/or CD3+ counts on the day prior to the leukapheresis procedure, maintenance of hematocrit levels at 40%, adequate venous access, blood prime of the leukapheresis instrument, prevention of hypocalcemia, and consideration for allowing for >1 day of leukapheresis for the pt to meet the acceptance criteria when medically feasible/safe. During leukapheresis, hypothermia must be prevented, and the pt must be monitored for hypocalcemia, hypomagnesemia, and alkalosis.Conclusions: Leukapheresis and tisagenlecleucel manufacturability in pediatric pts with r/r B-ALL <3 years old and low weight (lowest 6 kg, youngest 3.6 months) continues to be feasible and leukapheresis and manufacturing outcomes show an improvement over time. Communication among cross-functional teams within and between the institution and manufacturer have been key for achieving these advancements. Clinical outcome data for these pts are currently being explored. [Display omitted] DisclosuresWillert: Novartis Pharmaceuticals Corporation: Current Employment. Fong: Novartis Pharmaceuticals Corporation Canada: Current Employment. Clough: Novartis Pharmaceuticals Corporation: Current Employment. Magley: Novartis Pharmaceuticals Corporation: Current Employment. Shojaee: Novartis Pharmaceuticals Corporation: Current Employment. Tiwari: Novartis Healthcare Pvt. Ltd: Current Employment. Acker: Novartis Pharmaceuticals Corporation: Current Employment.

Pediatric Hydroxyurea Treatment Patterns, Sickle Cell Disease-Related Complication Rates, and Costs in a Large US Administrative Claims Database: A Retrospective Analysis

Introduction: Sickle cell disease (SCD) is an inherited blood disorder and hydroxyurea (HU) is the only pharmaceutical treatment approved for pediatric patients aged 9 months and older. In 2014, the National Heart, Lung, and Blood Institute (NHLBI) recommended that infants, children, and adolescents be offered treatment with HU regardless of disease severity to reduce SCD-related complications, such as pain and anemia. In 2017, the FDA approved HU in pediatric patients aged 2 and older to reduce the frequency of painful crises and the need for blood transfusions. This study aimed to describe SCD treatment patterns, SCD-related complications rates, and health care resource utilization and costs in pediatric patients with SCD using HU to identify gaps in care.Methods: This retrospective analysis of a large US commercial claims database included health plan enrollees aged 0-17 years old with 1+ SCD diagnosis code from July 1, 2013-March 31, 2020 (study period) and 1+ HU pharmacy claim from January 1, 2014-September 30, 2019 (identification period) in the Optum Research Database. Index date was defined as the first date with a HU claim. Patients were continuously enrolled for 6 months before (baseline period) and 6+ months after the index date (fixed 6-month and variable follow-up periods) and excluded if they had evidence of clinical trial participation or pregnancy amongst females. Demographics and the top five Agency for Healthcare Research and Quality (AHRQ) comorbidities were captured during baseline. Fixed 6-month follow-up treatment patterns included use of HU, short-acting opioids, and red blood cell transfusions. Follow-up rates of priapism among males, acute kidney injury (AKI), chronic kidney disease (CKD), stroke, and transient ischemic attack (TIA) per 1,000 person-years (PY), excluding those with baseline evidence, were calculated. Fixed 6-month follow-up all-cause health care resource utilization included ambulatory, emergency department (ED), and inpatient hospitalizations. Total all-cause health care costs included health plan- and patient-paid amounts and were calculated as per-patient-per-month (PPPM) to account for the variable follow-up period.Results: 160 pediatric patients met the selection criteria (mean [SD] age: 10 [4.5] years, 58.1% male, 53.13% HB-SS). Mean (SD) follow-up was 2.7 (1.7) years. Top five 6-month baseline AHRQ comorbidities were anemia: 154 (96.3%); respiratory infections: 65 (40.6%); asthma: 40 (25.0%); heart disease: 37 (23.1%), and other gastrointestinal disease 34 (21.3%). Nearly a third (32.5%) had baseline HU use and 74 (46.2%) continued HU use for 6+ months. Among 86 (53.8%) with < 6 months of HU use, 34 (39.5%) never restarted HU during the fixed 6-month follow-up period. Short-acting opioid use was observed in 65 (40.6%) of pediatric patients, with a median of 2 fills, and 25 (15.6%) had at least one red blood cell transfusion during the fixed 6-month follow-up period. SCD-complication rates per 1,000 PY for priapism among males, AKI, CKD, stroke and TIA were 16.4, 2.3, 11.9, 19.7, and 4.7, respectively. SCD-complication rates by age groups are shown in Table 1. In the first 6 months of HU treatment, 154 (96.3%), 59 (36.9%), and 37 (23.1%) had at least one ambulatory, ED, and inpatient hospitalization, respectively. Mean (SD) total all-cause health care costs in the first 6 months of HU treatment were $24,446 ($108,930), driven primarily by inpatient hospitalizations $17,467 ($103,639). Mean (SD) total PPPM costs in total follow-up were $2,703 ($5,028), attributed mostly to medical care $2,511 ($4,866).Conclusions: Despite a recommendation for HU use in pediatric patients with SCD, less than half of this large commercial claims study cohort had consistent HU use. Pediatric patients with recent or current HU use were noted to have SCD-related complications. Among patients with SCD less than 18 years old, health care costs were high. Notably, short acting opioid use and blood transfusions typically prescribed to alleviate pain and treat SCD-related complications were observed, demonstrating significant burden of disease. Alternative or concomitant SCD treatments for the pediatric population could potentially reduce SCD-related complications and associated health care costs when HU use alone may not be sufficient. [Display omitted] DisclosuresManwani: Novartis: Consultancy. Paulose: Novartis Pharmaceuticals Corporation: Current Employment. Yen: Novartis Pharmaceuticals: Current Employment; Merck & Co., Inc.: Current holder of stock options in a privately-held company, Ended employment in the past 24 months. Lee: Novartis Pharmaceuticals Corporation: Current Employment. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Real-World Efficacy and Safety Outcomes for Patients with Relapsed or Refractory (R/R) Aggressive B-Cell Non-Hodgkin's Lymphoma (aBNHL) Treated with Commercial Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Real-World Efficacy and Safety Outcomes for Patients with Relapsed or Refractory (R/R) Aggressive B-Cell Non-Hodgkin's Lymphoma (aBNHL) Treated with Commercial Tisagenlecleucel: Update from the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry

Association of Bridging Therapy Utilization with Clinical Outcomes in Patients Receiving Chimeric Antigen Receptor (CAR) T-Cell Therapy

Background: CAR T-cell therapy has altered the landscape of treatment options for patients with hematologic malignancies. Because CAR T-cell therapy involves manufacturing an autologous cellular product over a period of weeks, patients can receive bridging therapy while awaiting CAR T-cells. Currently there is no standard of care for use of bridging therapy. Moreover, data are lacking regarding the impact of bridging therapy use on clinical outcomes.Methods: We conducted a retrospective analysis of 236 patients who received CAR-T cell therapy at two tertiary care centers from 2/2016-12/2019. We abstracted clinical outcomes from review of the Electronic Health Record (EHR) including 1) overall response rate (ORR); 2) complete response (CR) rate; 3) progression-free survival (PFS); 4) overall survival (OS); 5) health care utilization (length of stay [LOS], intensive care unit [ICU] admission during admission for CAR T-cell therapy, and hospital readmission within 3 months of CAR T-cell infusion); and 6) rates of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) [all grades and grade 3+]. We assessed the association of bridging therapy use with ORR, CR rate, rates of ICU admission and hospital readmission, and rates of CRS (any grade) and ICANS (any grade and grade 3+) using the chi square test. We assessed the association of bridging therapy use with LOS using the Wilcoxon-Mann-Whitney test given the distribution of LOS and with grade 3+ CRS using Fisher's Exact Test given the sample size of this outcome. To assess the association of bridging therapy use with PFS and OS, we used Cox multivariable regression analyses adjusting for age, sex, marital status, Charlson comorbidity index, lymphoma diagnosis, number of prior therapies, history of autologous stem cell transplant, time from relapse to CAR T-cell therapy, vein to vein time, Eastern Cooperative Oncology Group performance status (closest to day 0), LDH (> 500 vs <=500), CRP, ferritin, and platelet count (< 100 vs >=100) prior to CAR T-cell infusion, CAR T-cell product, total dose of steroids received (days 0-31), and receipt of tocilizumab.Results: Patients had a median age of 62.8 years (range: 19-82) and the majority were male (145/236, 61.4%). The most common diagnosis was de novo diffuse large B cell lymphoma (DLBCL) (101/236, 42.8%) and most patients received axicabtagene ciloleucel (axi-cel) (192/236, 81.4%). All patients received lymphodepletion with cyclophosphamide and fludarabine. Overall, 39.4% (93/236) received bridging therapy. Regimens utilized for bridging therapy included systemic chemotherapy (48/236, 20.3%), corticosteroids (25/236, 10.6%), radiation (10/236, 4.2%), and other systemic therapies (10/236, 4.2%). Among the entire cohort, ORR and CR rate were 85.2% (201/236) and 64.8% (153/236), respectively, and bridging therapy use was not associated with ORR (80.0% with bridging therapy vs. 88.8% without bridging therapy; χ 2=3.81; p=0.051) or CR rate (63.4% with bridging therapy vs. 65.7% without bridging therapy; χ 2=0.13; p=0.718). In univariate Cox regression analyses, bridging therapy was associated with worse PFS (HR=1.47; p=0.049) and worse OS (HR=1.85; p=0.006). In multivariable Cox regression models adjusting for covariates (Tables 1 and 2), bridging therapy use was not associated with PFS (HR=1.43; p=0.163) but was associated with worse OS (HR=2.23; p=0.006). Bridging therapy use was not associated with LOS (p=0.451), ICU admission (χ 2=0.22; p=0.638), hospital readmission (χ 2=0.95; p=0.329), CRS (all grades: χ 2=0.46; p=0.500; grades 3+: p=0.574), or ICANS (all grades: χ 2=0.13; p=0.719; grades 3+: χ 2=0.23; p=0.632).Conclusions: We identified that bridging therapy use is not associated with differences in response rates, PFS, health care utilization, or rates of CRS or ICANS but is associated with worse OS in patients receiving CAR T-cell therapy. These findings underscore the need for novel bridging therapy regimens to optimize outcomes in this patient population. [Display omitted] DisclosuresJacobson: Celgene: Consultancy, Honoraria, Other: Travel support; Axis: Speakers Bureau; Humanigen: Consultancy, Honoraria, Other: Travel support; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; AbbVie: Consultancy, Honoraria; Nkarta: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Lonza: Consultancy, Honoraria, Other: Travel support; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Clinical Care Options: Speakers Bureau. Frigault: Novartis: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Arcellx: Consultancy; Iovance: Consultancy; Takeda: Consultancy; Editas: Consultancy; BMS: Consultancy.

Immune Profiles of Myeloma Tumor Microenvironment May Predict Sensitivity or Resistance to Elotuzumab

Background: Elotuzumab (ELO), an immunobiologic therapy targeting SLAMF7/CD319, is effective in the treatment of multiple myeloma (MM) with clinical indications in relapsed/refractory disease in combination with lenalidomide or pomalidomide. ELO binds SLAMF7 on the surface of MM cells to increase immune recognition while also binding SLAMF7 on NK cells resulting in the activation of an effector cell population capable of readily killing via antibody-dependent cellular cytotoxicity (ADCC) mechanisms. ELO efficacy has also been linked to enhanced antibody-dependent cellular phagocytosis (ADCP). Given the dependence of ELO activity on immune elements of the tumor microenvironment (TME), we hypothesized that characterization of the immunologic constituents of the immune TME (iTME) would provide cues capable of predicting clinical efficacy.Methods: Nineteen patients were enrolled on a single-center clinical trial run at Moffitt Cancer Center comparing clinical activity of ELO in combination with low-dose (10mg) vs high-dose (25mg) lenalidomide and dexamethasone in patients with biochemical relapse while on lenalidomide maintenance after first line therapy. Bone marrow aspirate (BMA) and peripheral blood (PB) samples we collected at baseline, after completion of 2 treatment cycles, and at time of progression. Cells isolated from the BMA were analyzed by multiparameter flow cytometry (MPFC) using 4 panels; 3 panels characterized lymphocytes according to maturation, activation and polarization (T H1, T H2, T H17 or T Reg) and a 4 th panel characterized myeloid elements. Data was acquired on a BD Symphony cytometer and analysis was performed using FlowJo software.Results: Patient samples were categorized according to initial therapeutic response. Responders (n=6) achieved >PR at best response, Progressors (n=5) were identified as patients whose disease markers increased >25% and Stable Disease (n=8) was identified as demonstrating <25% change in serologic disease markers. Here, we present a comparison of phenotypic profiles from the BM samples acquired at baseline before treatment initiation from patients classified as Responders or Progressors (patients demonstrating stable disease as best response were analyzed separately). Sample analysis by MPFC revealed distinct populations uniquely associated with responses as well as with treatment refractoriness. Principal component analysis (PCA) of the myeloid immune compartment shows 2 clusters representing distinct populations detectable only in Responders, while another large cluster, also expressing a granulocytic phenotype consistent with granulocytic myeloid suppressor cells, is prevalent in the Progressor patients but nearly absent from Responder patients, as might be predicted. Similarly, PCA identified monocyte/macrophage clusters uniquely associated with Responder or Progressor samples. Evaluation of lymphoid populations using 3 lymphoid panels also reveals distinctive clustering patters by PCA highlighting populations differentially associated with Responder or Progressor samples. Notably, while NK cells are present in all patient samples, there is a population of immature NK cells enriched in Responder patients that is largely absent from the Progressor population.Conclusion: Immune profiling of the myeloid and lymphoid components of the baseline BM iTME in MM prior to treatment with ELO reveals distinct patterns of cellular constitution associated with responsiveness or refractoriness to subsequent treatment. While NK cells are known to be important to the ELO mechanism of action, our data suggests that ELO activity is compromised in the absence of immature NK cells. This work suggests that measurable characteristics of the cellular components of the iTME may provide important cues to help predict ELO therapeutic efficacy. These observations will need to be confirmed in a larger data set. DisclosuresShain: Amgen Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi Genzyme: Consultancy, Speakers Bureau; Adaptive Biotechnologies Corporation: Consultancy, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GlaxoSmithLine, LLC: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen oncology: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Karyopharm Therapeutics Inc.: Honoraria, Research Funding. Baz: BMS, sanofi, Karyopharm, Janssen, AbbVie: Consultancy, Research Funding; Oncopeptides: Consultancy; GlaxoSmithKline: Consultancy, Honoraria; Merck: Research Funding. Nishihori: Novartis: Research Funding; Karyopharm: Research Funding.