KEYWORDSNon-small-cell lung cancer; Fibrinolysis; Coagulation;Tumor necrosis factor-alpha; D-Dimer; Thrombin-antithrombin complexes Summary The present study was designed to investigate whether a correlation exists between IL-6, TNF-␣ and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n = 65, 53 males, mean age 65 ± 8, adenocarcinoma n = 32, squamous cancer n = 33) or chronic obstructive pulmonary disease (COPD) (n = 65, 51 males, mean age 67 ± 9) were studied. As control group 65 healthy donors (51 males, mean age 61 ± 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 g/ml) compared either to COPD patients (1.1 g/ml, P < 0.05) or controls (0.3 g/ml, P < 0.0001). Positive TNF-␣ levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P < 0.002) and 5% of controls (P < 0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P < 0.001). Median TATc levels were elevated in either NSCLC (6.9 g/l) or COPD (5.7 g/l) patients compared to controls (1.8 g/l, P < 0.0001). Elevated D-dimer levels were significantly associated to positive TNF-␣ levels in patients without distant metastasis (F = 4.3, P < 0.05). Moreover, TNF-␣ levels (P < 0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-␣ might be responsible for an activation of fibrinolysis in patients with NSCLC.

Efficacy of alemtuzumab retreatment (course [C] 3) after the initial 2 courses were evaluated (CARE-MS II, NCT00548405; extension, NCT00930553). Patients received alemtuzumab retreatment (12 mg/day, 3 consecutive days;≥12 months apart) as needed for relapse and/or MRI activity or another disease-modifying therapy (DMT) per investigator’s discretion. Assessments 12 months before C3 and up to 3 years after C3: annualised relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus core study baseline); 6 month confirmed disability improvement (CDI). Patients receiving another DMT were excluded. Analyses included patients who received C3 or more, with data censored at the time of C4 if a fourth course was received. Through Year 6, 88% of patients entering the extension remained on study, with 45% receiving ≥1 retreatment. ARR decreased from 0.85 (12 months before C3) to 0.20 (12 months after C3; rate ratio [95% CI], 0.24 [0.17–0.34]; p<0.0001), and remained low (0.27) 3 years after C3. 68% of patients maintained stable/improved EDSS 12 months after C3. The percentage with CDI increased from 4% (12 months before C3) to 14% (12 months after C3; p=0.0126). These findings demonstrate the efficacy of alemtuzumab C3 in patients with disease activity after the initial 2 courses.Study support: Sanofi and Bayer HealthCare Pharmaceuticals.