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This study evaluated the long-term safety and efficacy of dapagliflozin as an adjunct to adjustable insulin in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) was a randomized (1:1:1), double-blind, placebo-controlled phase 3 study of dapagliflozin 5 mg and 10 mg in patients with type 1 diabetes (HbA 1c 7.5-10.5% [58-91 mmol/mol]) (NCT02268214). The results of the 52-week study, consisting of the 24-week short-term and 28-week extension period, are reported here. RESULTS Of the 833 patients randomized into the study, 708 (85%) completed the 52-week study. Over 52 weeks, dapagliflozin 5 mg and 10 mg led to clinically significant reductions in HbA 1c (difference vs. placebo [95% CI] 20.

Factor VIII (FVIII) activation by thrombin leads to proteolytic cleavage and loss of B-domain and formation of a heterotrimeric structure constituted by A2 domain linked by weak ionic interactions to A1 and A3-C1-C2 subunit. Dissociation of the A2 domain results in the formation of the heterodimeric inactive FVIII molecule. About 5% of haemophilia A patients show a normal concentration of FVIII antigen (FVIII:Ag) levels (at least 30% of normal) but markedly reduced FVIII activity (FVIII:C) suggesting dysfunctional FVIII protein; this type of haemophilia is known as cross-reacting material positive (CRM+) [1]. A subset of these patients with a mild phenotype exhibit a discrepancy between FVIII:C results elicited in one-stage and two-stage assays [2-4] and 11 mutations in the A1, A2, A3 and C domains have been identified so far as responsible for that in vitro phenomenon [5]. Arg 531 His is one of the best-characterized mutations, its molecular basis consisting of an increase in the dissociation rate of the A2 subunit from the activated FVIII (FVIIIa) heterotrimer which leads to increased rate of inactivation and discrepancies in the plasma FVIII concentrations elicited with different assays and assay conditions [3,6]; Arg 1966 Gln is, however, the most frequently found (10% of mild haemophiliacs overall and 38% of discrepant patients) and has similar pathogenetic consequences [5].

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1886 Poster Board I-909 Background: Approximately 30% of patients with multiple myeloma (MM) present with baseline renal impairement, with 1% to 13% having renal failure requiring dialysis support. The severity of renal impairment significantly affects the prognosis of patients with MM and has been associated with shorter survival or early death. Lenalidomide is an immunomodulating agent indicated for the treatment of MM patients after one prior therapy. Lenalidomide is primarily excreted unchanged by the kidney, adjustements to the starting dose are recommended in patients with moderate or severe renal impairement and in patients on dialysis. For patients with end stage renal disease (CLCr < 30 mL/min) requiring dialysis, the recommended starting dose is 5 mg/day. However, experience in patients with MM and dialysis support is limited. To further examine the safety and activity of lenalidomide-based therapy in these patients, we underwent a retrospective analysis in patients with MM who required dialysis at the time of lenalidomide administration. Methods: Fifteen patients (10 M/5 F; median age, 70 years, range 55–77) with relapsed MM from 10 Spanish hospitals received lenalidomide-based therapy between 2007 and 2009. All patients were on dialysis at the time of lenalidomide administration. Median (range) number of therapies previously administered was 2 (1–4) and median time between diagnosis and lenalidomide treatment was 14 months (range, 5–50). Eighty-seven percent of patients received lenalidomide at a dose of 15 mg/day three times weekly after dialysis given in combination with dexamethasone. Patients were given a median of seven 28-day cycles (range, 1–22 cycles) of lenalidomide treatment. Antithrombotic prophylaxis was administrated in fourteen patientes and consisted of low molecular weight heparin (five cases, 36%), oral anticoagulation (four cases, 29%), antiplatelet therapy (three cases, 21%), and combination of the above agents (two cases, 14%). Results: Overall, 13 (87%) patients experienced adverse events, with grade 3 neutropenia as the most common (8 patients). Seven patients (47%) developed grade 3–4 infectious complications (3 bacteremias, 1 infection of arterio-venous fistula, 1 septic arthritis, 1 central venous line infection, and two pneumonias in the remaining patient). No patient developed thromboembolic complications. Fourteen patients were evaluable for response: 4 had complete response (29%), 1 a very good partial response (7%), and 3 partial response (21%). In addition, 4 patients had stable disease (29%) and 2 (14%) did not respond. One patient became independent of dialysis following lenalidomide-based treatment. As of July 2009, seven (47%) patients have died, four due to infectious complications and three as a result of progressive disease. Eight patients are still alive, six of them continue on lenalidomide treatment and two discontinued therapy due to liver toxicity (1 case) and progressive disease (1 case). Conclusion>: These results suggest that lenalidomide-based regimens can be used in MM patients requiring dialysis, with a good response rate. The high incidence of neutropenia and infectious complications highlights the need of a close monitoring of these patients. Currently ongoing studies will more formally evaluate the impact of lenalidomide-based regimens in this patient population. Disclosures: No relevant conflicts of interest to declare.