Janssen-Cilag Pty Research Articles

Role of dithiothreitol in the resolution of pretransfusion immunohematology testing in patients receiving the anti-CD38 monoclonal antibody daratumumab for the treatment of multiple myeloma

Abstract: INTRODUCTION: Daratumumab (Darzalex; Janssen-Cilag Pty Ltd), an anti-CD38 monoclonal antibody (MoAb), has demonstrated high efficacy in treating relapsed and refractory multiple myeloma (MM). It stands as the pioneering anti-CD38 MoAb approved by the US FDA (2015) and TGA Australia (2017). While targeting CD38 on myeloma cells, daratumumab poses a challenge in pretransfusion testing by inducing panreactivity in indirect antiglobulin tests (IATs) due to CD38 expression on red cells. This study investigates the role of dithiothreitol (DTT) in resolving pretransfusion immunohematology testing in patients treated with daratumumab for MM. MATERIALS AND METHODS: Pretransfusion samples from three hematological patients diagnosed with MM and receiving anti-CD38 drugs necessitating red cell transfusion were subjected to immunohematology serological testing. Clinicians provided patient information, including gender, age, transfusion history, and time between anti-CD38 MoAb infusion and sample collection. Tests included ABO/RhD typing, IAT, both polyspecific and monospecific direct antiglobulin test (DAT), antibody (Ab) screening, Ab identification, eluate preparation, and red cell crossmatch. Control tests were conducted by incubating patient samples at 37°C for 1 h. RESULTS: ABO/RhD typing remained unaffected, yet all samples exhibited panreactivity in IATs. Two samples showed positive DAT results but negative eluates. Treatment of reagent red blood cells (RBCs) with 0.2 M DTT effectively mitigated interference by anti-CD38 monoclonal antibodies, resulting in compatible red cell crossmatches. Notably, incubation of patient samples at 37°C for 1 h yielded identical results. CONCLUSION: Pretreatment of erythrocytes with DTT deactivated the CD38 antigen, eliminating reactivity with patient serum treated with daratumumab. DTT treatment of reagent RBCs emerges as an efficient and accessible strategy to counteract interference from anti-CD38 drugs in pretransfusion tests.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: The optimal treatment for very elderly patients (pts) with newly diagnosed Diffuse Large B Cell Lymphoma (DLBCL) remains controversial. R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with a 2 yr OS of 59% and PFS of 47% (Peyrade et al., Lancet Oncol 2011). We present our final data from this prospective Phase II study of ibrutinib, rituximab and mini-CHOP in pts ≥75 yrs with newly diagnosed DLBCL. Methods: Pts received six 21-day cycles of ibrutinib 560 mg daily and R-mini-CHOP (Rituximab 375 mg/m2, cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, vincristine 1 mg on day 1 & prednisone 40 mg/m2 or 100 mg/d × 5) followed by an additional two 21 day cycles of rituximab + ibrutinib (or high dose methotrexate for CNS prophylaxis). Primary endpoints were deliverability and 2 year overall survival (OS). Sample size calculations were made using a one-sample two-sided approach to detect a 15% improvement on the fixed Peyrade reference OS (59%) and PFS (47%) rates. Results: Eighty pts were recruited from Nov 2015 to Nov 2018. One died prior to receiving treatment and is not included in the analysis. Median age was 82 yrs (75–95); 81% stage III/IV; 54% age adjusted IPI 2–3. With a median follow-up of 35.5 months (m) (0.2, 71.7) (data cut 6 September 2022), there was a non-significant trend towards improvement in 2-year OS of 68% (55.6%, 77.4%) compared to the reference Peyrade cohort of 59% (p = 0.11). Median OS was 72 m (95% CI 35 m to not reached (NR)). Median 2-year PFS of 60.0% (47.7%, 70.3%) was significantly improved compared to the reference cohort of 47% (p = 0.03), with a median PFS of 40 m (95% CI 20.41, NR). Overall response assessment assessed by investigators at the end of treatment was 76% (61/80 pts), with a complete response rate of 70% (56/80 pts). All 6 cycles of R-mini-CHOP were completed in 63/79 pts (80%) and 57/79 pts (71%) completed all 8 cycles of therapy. The median Average Relative Total Dose and Average Relative Dose Intensity for the entire regimen was 97% (IQR 82, 100; 88, 100). 34/79 pts (43%) have died, 17 due to progressive disease and 5 were treatment-related. 67% pts experienced an SAE. Most common AEs were infections and diarrhoea (majority grade 1–2). In the EORTC QLQ-C30 there was an improvement in functional and symptom scales and on the EQ-5D-5L survey, there was a significant improvement in the median health state classification score and median visual analogue scale thermometer score over time. Encore Abstract - previously submitted to EHA 2023 The research was funded by: Janssen-Cilag Pty Ltd. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Combination Therapies Conflicts of interests pertinent to the abstract. E. Verner Research funding: Janssen-Cilag Pty Ltd. E. Hawkes Consultant or advisory role: Janssen-Cilag Pty Ltd. T. Cochrane Consultant or advisory role: Janssen Cilag Pty Ltd. C. Y. Cheah Consultant or advisory role: Janssen-Cilag Pty Ltd. Honoraria: Janssen-Cilag Pty Ltd. M. K. Gandhi Research funding: Janssen-Cilag Pty Ltd. B. E. Butcher Other remuneration: Janssen Cilag Pty Ltd. J. Trotman Research funding: Janssen-Cilag Pty Ltd.

Preliminary findings from a risk stratification, quality of life and burden of illness in pulmonary arterial hypertension pilot study

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Janssen Australia and New Zealand (Janssen-Cilag Pty Ltd) Pulmonary Arterial Hypertension (PAH) management strategies focus on lowering mortality risk, extending the patient’s life span through the control and alleviation of disease symptoms, improving Quality of Life (QoL) and decreasing the burden of illness. This paper describes preliminary results of an Investigator Initiated pilot study exploring the relationship between PRO measures (PAH-SYMPACT, EQ5D5L); Burden of Illness assessment; and the ESC/ERS Risk Stratification. Findings Measures of PAH risk and QoL were assessed in 42 patients presenting to the IPAH clinic for management; mean age 69.2 [range 39, 84]; females 35 (83.3%), males 7 (16.7%). Tools analysed and compared included: PAH-SYMPACT and EQ-5D-5L as PRO and QoL measures; and ESC-ERS PAH risk stratification criteria to assess mortality risk. Health utility scores were derived from existing value sets: there was a 20% median reduction in QALYs for our patient population, with detrimental effects being more marked in those patients with greater impairment of EQ-5D-5L physical and cognitive-emotional domains (respectively: r = -0.92, p<0.001; and r = -0.85, p<0.001), PAH-SYMPACT physical domain reduction (r = -0.59, p<0.01), and PAH-SYMPACT cardiovascular symptoms (r = 0.64), p<0.01) and cardiorespiratory (r = 0.64, p<0.01) involvement. Physical domain scores were highly correlated for the two PROs studied (r = 0.74, p<0.001), but an unexpected poor correlation was seen in the cognitive/emotional domain (non-significant negative correlation) which requires further exploration. Unsurprisingly, EQ-5D-5L Visual Analogue Score for well-being was inversely correlated with physical domain impairment (r = -0.59, p<0.01), although it was noted that this did not apply for the cognitive/emotional domain. The agreement between tools was variable, with highest concordance seen for assessment of the physical domain (r = 0.74, p<0.001), and this raises the need to further define the merits of disease-specific (PAH-SYMPACT) vs generic (EQ-5D-5L) PRO analytic approaches. Tools examined in this study were well-correlated with symptomatic impairment, but neither PRO tool correlated with established risk markers as characterized in compound prognostic guides such as ESC-ERS criteria. Conclusions The fact that PRO indices showed little correlation with established risk stratification markers implies that the information provided by PROs is not redundant, and it is yet be assessed whether the incorporation of PRO’s may add further to the precision of risk assessment, a little-studied area which this group is further exploring. There should be more widespread and uniform use of PRO measures as part of standard PAH management.

Sequential Blinatumomab with Reduced Intensity Chemotherapy in the Treatment of Older Adults with Newly Diagnosed Ph Negative B-Precursor Acute Lymphoblastic Leukemia - Interim Analysis of the Australasian Leukemia and Lymphoma Group ALL08 Study

Sequential Blinatumomab with Reduced Intensity Chemotherapy in the Treatment of Older Adults with Newly Diagnosed Ph Negative B-Precursor Acute Lymphoblastic Leukemia - Interim Analysis of the Australasian Leukemia and Lymphoma Group ALL08 Study

SEQUOIA: Results of a Phase 3 Randomized Study of Zanubrutinib versus Bendamustine + Rituximab (BR) in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

SEQUOIA: Results of a Phase 3 Randomized Study of Zanubrutinib versus Bendamustine + Rituximab (BR) in Patients with Treatment-Naïve (TN) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Preliminary Safety and Efficacy Data from Patients (Pts) with Relapsed/Refractory (R/R) B-Cell Malignancies Treated with the Novel B-Cell Lymphoma 2 (BCL2) Inhibitor BGB-11417 in Monotherapy or in Combination with Zanubrutinib

Preliminary Safety and Efficacy Data from Patients (Pts) with Relapsed/Refractory (R/R) B-Cell Malignancies Treated with the Novel B-Cell Lymphoma 2 (BCL2) Inhibitor BGB-11417 in Monotherapy or in Combination with Zanubrutinib

Efficacy of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma: Primary Analysis of the Australasian Leukaemia & Lymphoma Group NHL29 Study

Efficacy of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma: Primary Analysis of the Australasian Leukaemia & Lymphoma Group NHL29 Study

Results of a Phase 2, Randomized, Double-Blind Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)

Results of a Phase 2, Randomized, Double-Blind Study of Sorafenib Versus Placebo in Combination with Intensive Chemotherapy in Previously Untreated Patients with FLT3-ITD Acute Myeloid Leukemia (ALLG AMLM16)

Response Rates and Quality of Life Outcomes in Australasian Leukaemia & Lymphoma Group NHL29: A Phase II Study of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma

Response Rates and Quality of Life Outcomes in Australasian Leukaemia & Lymphoma Group NHL29: A Phase II Study of Ibrutinib, Rituximab and Mini-CHOP in Very Elderly Patients with Newly Diagnosed Diffuse Large B Cell Lymphoma

Preliminary Minimal Residual Disease Analysis of the Australasian Leukaemia & Lymphoma Group (ALLG) ALL8 Study of Front-Line Blinatumomab with Chemotherapy in Adults with Ph Negative B-Cell Acute Lymphoblastic Leukaemia

Preliminary Minimal Residual Disease Analysis of the Australasian Leukaemia & Lymphoma Group (ALLG) ALL8 Study of Front-Line Blinatumomab with Chemotherapy in Adults with Ph Negative B-Cell Acute Lymphoblastic Leukaemia

Efficacy and Safety of Zanubrutinib in Patients with Treatment-Naive Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with Del(17p): Initial Results from Arm C of the Sequoia (BGB-3111-304) Trial

Efficacy and Safety of Zanubrutinib in Patients with Treatment-Naive Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with Del(17p): Initial Results from Arm C of the Sequoia (BGB-3111-304) Trial

Multiple Chronic Comorbidities in a T2DM Mediterranean Population

Objective: T2DM patients often have multiple comorbidities which may impact patients’ management approach and treatment selection. This is the first study examining the co-prevalence of comorbidities such as CVD and CKD (GFR <60 ml/min and/or UACR ≥ 30 mg/g) across T2DM patients in Spain using a well-validated local database (DB). Methods: Retrospective cross-sectional study using the Spanish local electronic records DB “Information System for the Development of Research in Primary Care”, SIDIAP. Adult patients with T2DM were included and comorbid conditions were assessed using all medical records available from full years 2015-2016. Patient characteristics, laboratory measures and comorbidities were summarized via descriptive analyses, overall and by subgroups of age, gender and HbA1c levels. Results: From 373,185 T2DM identified patients (overall population, OP), 55% were men, their mean age was 70 years, the mean T2DM duration was 9 years and the mean HbA1c value was 7.12% (SD 1.32). The most common comorbid conditions were hypertension (HTN): 72% of patients; hyperlipidemia (HL): 60%; obesity: 39%, CKD: 33% and CVD: 23%. The highest co-prevalence was the combination of HTN/HL (45.2%), followed by HTN/CKD (28.3%), HTN/CVD (18.8%) and CVD/HL (15.1%). CVD was more frequent in older groups (32.3% in patients ³75 years-old) and in men (27.8% vs. 17.6%), while heart failure was more frequent in women (8.0% vs. 6.1%). CKD was found to increase with age, reaching 51.9% in patients ≥75 years. The coexistence of CKD and CVD in the whole population was 11.1%. Among T2DM patients with CVD and available GFR data (79,158, 91% of CVD patients), 57.6% had a GFR ≥ 60 ml/min (around 12% of OP), whereas 20.7% had GFR from 45 to <60, 14.2% had GFR from 30 to <45; 6.2% had GFR from 15 to <30ml/min; and 1.3% had GFR < 15ml/min. Conclusion: The frequency of comorbidities in T2DM patients from a Mediterranean area is high, and both age and gender play a role in overall comorbidity burden. CKD and CVD are frequent comorbid conditions among T2DM patients. Disclosure J. Franch-Nadal: None. M. Mata-Cases: None. J. Real: None. K. Ferreira de Campos: Employee; Self; Merck Sharp & Dohme Corp. M. Cedenilla: Employee; Self; Merck Sharp & Dohme Corp. A. Gómez: Employee; Self; Merck Sharp & Dohme Corp. D. Mauricio: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Eli Lilly and Company, GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen-Cilag Pty Limited. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi.

Achievement of Individualized HbA1c Targets with Self- vs. Physician-Led Titration of Basal Insulin (BI) in People with Type 2 Diabetes (T2DM), Newly or Recently Initiated on BI—Results from the DUNE Real-World Study

DUNE was a 12-week, prospective, observational study of 3139 adults with T2DM, newly (at enrollment) or recently (<12 months) initiated on BI. We evaluated the achievement of individualized HbA1c targets at 12 weeks according to self- vs. physician-led insulin titration. Irrespective of titration method, the proportion of participants who achieved their individualized HbA1c target at week 12 was <30% in both the newly- and recently- initiated BI groups (Table). For both titration groups, there were comparable improvements in fasting plasma glucose from baseline and similar incidence of hypoglycemia. Increase in total daily BI dose for self- vs. physician-led titration in the recently initiated BI group was 4.85 vs. 4.91 U, respectively, while in newly initiated individuals it was 9.68 vs. 7.77 U, respectively. Most participants who were self-titrating did so every 1-3 days, compared with no more frequently than every week for most participants who had physician-led titration. In all groups, the most frequently utilized dose increment was 2 U. The inability of most participants to achieve their target HbA1c in a real-world scenario, irrespective of the method of titration, warrants further investigation. Disclosure L. Berard: Other Relationship; Self; Abbott, Becton, Dickinson and Company, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Montmed Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada. Consultant; Self; Ascensia Diabetes Care. Other Relationship; Self; Novo Nordisk Inc., Merck & Co., Inc. D. Mauricio: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Eli Lilly and Company, GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen-Cilag Pty Limited. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. K. Khunti: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Sanofi-Aventis, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Sanofi-Aventis, Pfizer Inc.. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; Novo Nordisk A/S. Consultant; Self; Pfizer Inc.. Research Support; Self; Novo Nordisk A/S. D.R. Franco: Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Medtronic MiniMed, Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Eli Lilly and Company. Speaker's Bureau; Self; Abbott. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. C. Candelas: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. R. Perfetti: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association.

Self-Titration with Insulin Glargine 300 or 100 U/mL has Improved Efficacy vs. Physician-Led Titration—Comparison of the TAKE-CONTROL, AT.LANTUS, and ATLAS Studies in People with Type 2 Diabetes (T2DM)

Empowering individuals to self-titrate their basal insulin may help to reduce rates of sub-optimal titration often observed in clinical practice and help more people achieve HbA1c goals. Here we compare the results from the recently completed TAKE CONTROL study, which evaluated self-titration and physician-led titration of insulin glargine 300 U/mL (Gla-300) in people with T2DM, with comparable studies (AT.LANTUS and ATLAS) of insulin glargine 100 U/mL (Gla-100). All 3 studies were 24-week, multicenter, randomized, open-label, parallel-group studies. Fasting blood glucose targets were 80-130 mg/dL (4.4-7.2 mmol/L) in TAKE CONTROL, ≤100 mg/dL (5.5 mmol/L) in AT.LANTUS and ≤110 mg/dL (6.1 mmol/L) in ATLAS. Mean baseline HbA1c was between 8.4 and 8.9% (Table). Self-titration statistically significantly lowered mean HbA1c by 0.97 to 1.40% vs. physician-led titration (0.84 to 1.25%; p<0.for all 3 studies). The incidence of severe hypoglycemia and other safety outcomes was similar between titration arms in all 3 studies (Table). Both Gla-300 and Gla-100 were effective in improving glycemic control. Self-titration with Gla-300 resulted in significantly improved glycemic control vs. physician-led titration, as demonstrated previously with Gla-100, without increased hypoglycemia. Disclosure M. Davies: Advisory Panel; Self; AstraZeneca. Board Member; Self; AstraZeneca. Consultant; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Board Member; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Advisory Panel; Self; Eli Lilly and Company. Board Member; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc.. Board Member; Self; Janssen Pharmaceuticals, Inc.. Consultant; Self; Janssen Pharmaceuticals, Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Board Member; Self; Novo Nordisk Inc.. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Board Member; Self; Sanofi-Aventis. Consultant; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Advisory Panel; Self; Servier. Consultant; Self; Intarcia Therapeutics, Inc.. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. E. Boelle-Le Corfec: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. M. Odawara: Speaker's Bureau; Self; Sanofi, Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Eli Lilly and Company. Advisory Panel; Self; Sanofi, Novo Nordisk Inc., Eli Lilly and Company. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. J. Sieber: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. D. Russell-Jones: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly and Company, Novartis, Novo Nordisk, Sanofi. K. Strojek: Research Support; Self; AstraZeneca. Other Relationship; Self; Sanofi-Aventis, Novo Nordisk A/S. Speaker's Bureau; Self; Servier, Eli Lilly and Company, MSD K.K., Boehringer Ingelheim GmbH. Research Support; Self; Pfizer Inc., Amgen Inc.. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG.

Diabetes Treatment in Patients with Renal Disease—How Many Are Receiving Contraindicated Drugs?

Objective: To estimate the CKD (GFR <60 ml/min and/or UACR ≥ 30 mg/g) prevalence among T2DM patients and evaluate the use of antidiabetic drugs based on renal function. Methods: Retrospective, cross-sectional study, analyzing data from the Spanish electronic records database “Information System for the Development of Research in Primary Care, SIDIAP”, from Jan, 2015 to Dec, 2016. The use of antidiabetic drugs for each stage of chronic renal failure (CRF; GFR<60 mL/min) was evaluated in patients with available records of GFR. Furthermore, the adjusted RR for 5 events (global mortality, cardiovascular mortality, renal failure treated with dialysis or transplantation, acute renal failure and progression of kidney disease) according to KDIGO 2012 guidelines were assessed in those patients with available registers of both UACR and GFR. Results: From the overall T2DM study population (373,185), 33% (122,296) had CKD, of those, 48% were women, with a mean age of 76 years, a mean T2DM duration of 11 years and a mean HbA1c value of 7.2% (SD 1.37). A total of 336,198 patients (90%) had GFR data, and 94,240 (28%) had CRF. Among those with GFR 30 to < 45 mL/min (29,038; 8.9%), metformin was the most frequently used drug (49.6%), followed by insulin (33.5%), DPP-4i (21%) and sulfonylureas (15.9%). Among patients with GFR < 30 mL/min (13,262, 4%), insulin was the most used drug (50%), followed by DPP-4i (23%), metformin (16%), repaglinide (16%) and sulfonylureas (6.1%). The KDIGO 5 event-adjusted RR distribution among the 236,830 patients with available values of both UACR and GFR was: Low: 60.9%; Mild: 21.6%, High: 9.8% and Very high: 7.7%. Conclusion: CKD is a very frequent comorbidity among T2DM patients. The use of antidiabetic drugs is more complex in these patients because many people with kidney disease are often elderly, and have long lasting disease and significant comorbidities. A relevant number of T2DM patients are still treated with contraindicated antidiabetic drugs regarding their renal function. Disclosure M. Mata-Cases: None. J. Franch-Nadal: None. J. Real: None. K. Ferreira de Campos: Employee; Self; Merck Sharp & Dohme Corp. M. Cedenilla: Employee; Self; Merck Sharp & Dohme Corp. A. Gómez: Employee; Self; Merck Sharp & Dohme Corp. D. Mauricio: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Eli Lilly and Company, GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen-Cilag Pty Limited. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi.

Efficacy of IDegLira vs. Basal-Bolus Therapy in Subjects with Type 2 Diabetes in DUAL VII by Baseline Characteristics

In 5subjects with type 2 diabetes uncontrolled on metformin and basal insulin, the DUAL VII trial (NCT02420262) demonstrated that a once-daily injection of insulin degludec/liraglutide (IDegLira) was non-inferior to multiple injections of basal-bolus therapy (insulin glargine 100 units/mL + insulin aspart before each main meal) for A1C reduction, and was associated with a significantly lower risk of hypoglycemia. This non-prespecified post-hoc analysis examined whether the efficacy results persisted across sub-groups for six different variables and evaluated whether benefits seen in the trial were applicable across a broad patient population. After 26 weeks of treatment, there was no significant difference in A1C reduction between IDegLira compared with basal-bolus in any baseline characteristic group (A1C, BMI, age, diabetes duration, total daily insulin dose and fasting plasma glucose [Table]). Additionally, there was no significant interaction between treatment and baseline sub-group for any of the baseline characteristics (Table). In conclusion, the A1C lowering was comparable between once-daily IDegLira vs. basal-bolus therapy after 26 weeks of treatment, irrespective of baseline characteristics, which underscores the general application of these findings to a broad patient population. Disclosure L.K. Billings: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Consultant; Self; Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S, Dexcom, Inc. D.C. Klonoff: Consultant; Self; Ascensia Diabetes Care, Lifecare, Intarcia Therapeutics, Inc., Voluntis USA, Novo Nordisk Inc., Onduo, Trividia Health, Inc., American Diabetes Association, The Endocrine Society, American Association of Diabetes Educators. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG. R. Grøn: Employee; Self; Novo Nordisk A/S. N. Halladin: Employee; Self; Novo Nordisk A/S. E. Jódar: Advisory Panel; Self; Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Research Support; Self; Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Pfizer Inc., Sanofi. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S.

Change in Insulin Dose and HbA1c by Geographical Region—Results from the Diabetes Unmet Need with Basal Insulin Evaluation (DUNE) Study

DUNE, a 12-week, prospective, observational study (Feb 2015–Jul 2016) of 3139 people with T2DM, either newly (at enrollment) or recently (<12 months, mean 5.7 months) initiated on basal insulin (BI), aimed to assess the impact of symptomatic hypoglycemia on individualized HbA1c target achievement. Only 27.9% and 26.8% of newly and recently initiated participants, respectively, achieved individualized HbA1c targets. This analysis investigated the regional variations in BI dose and HbA1c change from baseline, which may help characterize treatment practices associated with improved target achievement. Mean baseline daily BI dose across regions ranged from 0.14 to 0.21 U/kg for newly initiated and 0.25 to 0.39 U/kg for recently initiated participants. Mean baseline HbA1c ranged from 8.94 to 9.44% (newly initiated), and 8.39 to 8.78% (recently initiated) across regions. In general, HbA1c reductions were greater in newly vs. recently initiated participants, and accompanied by greater increases in daily insulin dose (Figure), except in Nordic Europe, where HbA1c reductions were similar despite a ∼3-fold difference between groups in BI dose increases from baseline. These results show that the relationship between BI dose increase and HbA1c reduction can be variable, potentially reflecting regional differences in practices or populations that warrant further analysis. Disclosure D. Mauricio: Advisory Panel; Self; AstraZeneca. Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Eli Lilly and Company, GlaxoSmithKline plc.. Research Support; Self; GlaxoSmithKline plc.. Advisory Panel; Self; Janssen-Cilag Pty Limited. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Board Member; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Sanofi. Board Member; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Research Support; Self; Sanofi. L. Meneghini: Advisory Panel; Self; Novo Nordisk Inc., Sanofi US. Consultant; Self; Sanofi US, Novo Nordisk Inc.. Advisory Panel; Self; Intarcia Therapeutics, Inc.. Other Relationship; Self; American Diabetes Association. E. Orsi: None. V. Klimontov: None. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. R. Perfetti: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. K. Khunti: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Sanofi-Aventis, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Sanofi-Aventis, Pfizer Inc.. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Takeda Development Centre Europe Ltd., Servier. Research Support; Self; Novo Nordisk A/S. Consultant; Self; Pfizer Inc.. Research Support; Self; Novo Nordisk A/S.

Switching to Insulin Degludec from Insulin Glargine U100 Improves Glycemic Control in People with Type 1 (T1D) or Type 2 diabetes (T2D) in a Real-World Setting

EU-TREAT (NCT02662114), a European, multicenter, retrospective chart review study investigated the clinical impact of switching from any basal insulin to insulin degludec (degludec). This analysis aimed to evaluate the effectiveness of degludec after switching from insulin glargine 100 units/mL (glargine U100), under routine care. Patients with T1D or T2D were switched, based on clinical judgement, from glargine U100 to degludec at least 6 months before data collection. Baseline was defined as the most recent recording during the 3-months pre-switch period. Outcome data were collected at 6 ± 3 months and at 12 ± 3 months pre- and post-switch. BothHbA1c and fasting plasma glucose (FPG) decreased significantly in patients with T1D (n=889) or T2D (n=259) at 6- and 12-months post-switch vs. pre-switch (all p<0.001, except for FPG at 12-months post-switch in T2D, p=0.023). Daily insulin dose decreased significantly in patients with T1D at 6- and 12-months post-switch vs. pre-switch (both p<0.001), but remained unchanged in patients with T2D. Hypoglycemia was significantly lower (all p<0.05) post-switch vs. pre-switch (Figure). Switching to degludec from glargine U100 significantly reduces HbA1c and risk of hypoglycemia under routine care. Disclosure S.T. Knudsen: Advisory Panel; Self; Novo Nordisk A/S, Merck & Co., Inc., Sanofi-Aventis, Eli Lilly and Company, Boehringer Ingelheim GmbH, AstraZeneca. Speaker's Bureau; Self; Merck & Co., Inc., Boehringer Ingelheim GmbH, AstraZeneca. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG. B. Schultes: Advisory Panel; Self; Novo Nordisk A/S, Sanofi, AstraZeneca, Eli Lilly and Company, Bayer AG, Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Sanofi, Eli Lilly and Company, MSD K.K., Bayer AG, Boehringer Ingelheim GmbH. A. Lapolla: None. M. Eidenmueller: Research Support; Self; Novo Nordisk A/S, Sanofi, AstraZeneca. Speaker's Bureau; Self; Berlin-Chemie AG. R. Prager: Advisory Panel; Self; Novo Nordisk A/S, Eli Lilly and Company, MSD K.K., Sanofi-Aventis, Boehringer Ingelheim GmbH, AstraZeneca. A. Catarig: Employee; Self; Novo Nordisk Region Europe Pharmaceuticals A/S. Employee; Spouse/Partner; GlaxoSmithKline plc. M.L. Wolden: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Siegmund: Advisory Panel; Self; Abbott, Ascensia Diabetes Care, Bayer Vital GmbH, Boehringer Ingelheim GmbH, Eli Lilly and Company, Janssen, Medtronic, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Becton, Dickinson and Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Bristol-Myers Squibb Company, Berlin-Chemie AG, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Sanofi.

Self-Managed Titration with Insulin Glargine 300 U/mL (Gla-300) Can Achieve Similar Efficacy to Physician-Led Titration Regardless of Prior Insulin Status in People with T2DM—Results from TAKE CONTROL

Many people with T2DM do not achieve HbA1c goals in clinical practice, owing in part to sub-optimal basal insulin titration. TAKE CONTROL, a 24-week, multicenter, randomized, open-label, parallel-group study, compared the efficacy and safety of a Gla-300 titration algorithm (fasting self-monitored plasma glucose >130 mg/dL, +3 U; <80 mg/dL, −3 U), when self-managed or led by physicians. Overall, improved glycemic control without increased hypoglycemia was seen with self-titration. Here, we report results stratified by prior insulin use. At baseline, mean HbA1c was higher in the insulin-naïve vs. prior-insulin group (Table). In both groups, self-titration and physician-led titration resulted in similar HbA1c reduction. For confirmed or severe hypoglycemia, there was no evidence of heterogeneity between titration approaches for both glycemic thresholds (≤70 mg/dL or <54 mg/dL). Glycemic goal achievement with Gla-300 using self-titration was similar to that reported for physician-led titration, regardless of prior insulin use, but with reduced or similar risk of hypoglycemia. Empowering people with T2DM to self-titrate their basal insulin effectively upon Gla-300 initiation, or after switching to Gla-300, can improve glycemic target achievement without increasing hypoglycemia. Disclosure E. Delgado: Advisory Panel; Self; AstraZeneca. Speaker's Bureau; Self; AstraZeneca, Novo Nordisk A/S. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi-Aventis. Research Support; Self; Sanofi-Aventis. Speaker's Bureau; Self; Esteve, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Abbott. Speaker's Bureau; Self; Lilly. Research Support; Self; Menarini Group. M. Bonnemaire: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. A. Dauchy: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. V. Donicova: None. M. Kvapil: None. N. Tentolouris: Advisory Panel; Self; MSD K.K., AstraZeneca, Sanofi, Novo Nordisk A/S, Elpen Pharmaceutical Co. Inc., Eli Lilly and Company, Boehringer Ingelheim GmbH, Novartis AG. Research Support; Self; MSD K.K., Eli Lilly and Company, Novo Nordisk A/S, Sanofi, Pfizer Inc., AstraZeneca, Janssen-Cilag Pty Limited, GlaxoSmithKline plc., Novartis AG. L. Popescu: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. D. Russell-Jones: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim, Cellnovo, Eli Lilly and Company, Novartis, Novo Nordisk, Sanofi.

Considerations for pre-transfusion immunohaematology testing in patients receiving the anti-CD38 monoclonal antibody daratumumab for the treatment of multiple myeloma.

In recent years, the anti-CD38 monoclonal antibody daratumumab (Darzalex; Janssen-Cilag Pty Ltd) has been shown to be highly efficacious in relapsed and refractory multiple myeloma, with the final results of treatment in newly diagnosed patients awaited. Despite awareness of the potential interference of daratumumab in pre-transfusion immunohaematology testing during phase I and II clinical studies, there was a degree of unpreparedness in the community upon the introduction of this drug into the clinics, particularly the impact that it has on the operational processes in hospital transfusion laboratories and timely issue of red blood cells (RBCs). Anti-CD38 interference in pre-transfusion immunohaematology tests is a particular problem in patients being treated with daratumumab for multiple myeloma as many will require RBC transfusions during their disease treatment. Panagglutination caused by anti-CD38 monoclonal antibody during the indirect antiglobulin test may mask the presence of a clinically significant RBC alloantibody in the patient's plasma during the antibody screen and identification process, which may be overlooked, particularly in urgent situations, subsequently resulting in a delayed or acute haemolytic transfusion reaction. Here, we summarise daratumumab's effects on pre-transfusion immunohaematology testing and its impact on clinical practice and make practical recommendations based on a consensus from medical and scientific transfusion experts and myeloma specialists on behalf of the Australian and New Zealand Society of Blood Transfusion and Myeloma Scientific Advisory Group to Myeloma Australia, respectively.