on behalf of the LBSL02/99 Study GroupObjective. To evaluate the safety profile of longterm belimumab therapy combined with standard therapy for systemic lupus erythematosus (SLE) in patients with active disease.Methods. Patients who were randomized to receive intravenous placebo or belimumab 1, 4, or 10 mg/ kg, plus standard therapy, and completed the initial 52-week double-blind treatment period were then allowed to enter a 24-week open-label extension phase. During the extension period, patients in the belimumab group either received the same dose or were switched to 10 mg/kg and patients in the placebo group were switched to belimumab 10 mg/kg. Patients who achieved a satisfactory response during the 24-week extension period were allowed to participate in the long-term continuation study of monthly belimumab 10 mg/kg. Adverse events (AEs) and abnormal laboratory results were analyzed per 100 patient-years in 1-year intervals.Results. Of the 364 patients who completed the 52-week double-blind treatment period, 345 entered the 24-week extension, and 296 continued treatment with belimumab in the long-term continuation study. Safety data through 4 years of belimumab exposure (1,165 cumulative patient-years) are reported. Incidence rates of AEs, severe/serious AEs, infusion reactions, infections, malignancies, grades 3/4 laboratory abnormalities, and discontinuations due to AEs were stable or declined during 4-year belimumab exposure. The most common AEs included arthralgia, upper respiratory tract infection, headache, fatigue, and nausea. Serious infusion reactions were rare: only 1 occurred during the 4-year followup period. Rates of serious infection decreased from 5.9/100 patient-years to 3.4/100 patientyears, and no specific type of infection predominated.Conclusion. Belimumab added to standard therapy was generally well-tolerated over the 4-year treatment period in patients with SLE, which suggests that ClinicalTrials.gov identifiers: NCT00071487 and NCT00583362.

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Background:We conducted a multicentre Phase 1b/2 trial to evaluate the safety and efficacy of mapatumumab, a fully human agonistic monoclonal antibody to the tumour necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) in patients with relapsed non-Hodgkin's lymphoma (NHL).Methods:Forty patients with relapsed or refractory NHL were treated with either 3 or 10 mg kg−1 mapatumumab every 21 days. In the absence of disease progression or prohibitive toxicity, patients received a maximum of six doses.Results:Mapatumumab was well tolerated, with no patients experiencing drug-related hepatic or other dose-limiting toxicity. Three patients with follicular lymphoma (FL) experienced clinical responses, including two with a complete response and one with a partial response. Immunohistochemistry staining of the TRAIL-R1 suggested that strong staining in tumour specimens did not appear to be a requirement for mapatumumab activity in FL.Conclusions:Mapatumumab is safe and has promising clinical activity in patients with FL.

Ongoing clinical trials will provide important information regarding the future development of TRAIL-R agonists.

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