Levofloxacin Prophylaxis in Newly Diagnosed Myeloma Patients

Background: Myeloma causes profound immunodeficiency and recurrent, serious infections. There are approximately 5,500 new UK cases of myeloma per annum; a quarter will have a serious infection within 3 months of diagnosis. Newly diagnosed patients may benefit from antibiotic prophylaxis to prevent infection and early death but this may be associated with healthcare-associated infections (HCAI). Methods: The TEAMM trial was a multicentre randomised, double-blind, placebo-controlled trial in newly-diagnosed myeloma patients randomised to receive Levofloxacin or placebo for 12 weeks at the start of anti-myeloma treatment. Follow-up was 4-weekly to 16 weeks and again at 1 year. The primary outcome was time to first febrile episode or death in the first 12 weeks from start of trial treatment. Secondary outcomes included number of infections, deaths, healthcare-associated organism carriage and invasive infections, and overall survival (OS). Findings: 977 patients were randomised (489 levofloxacin, 488 placebo). Primary events (febrile episodes, deaths, febrile episodes with death) in levofloxacin versus placebo arms were 19% vs 27% (87, 4, 4 vs 112, 15, 7), respectively; HR=0.66 (95% CI 0.51-0.86) p=0.002. There was no difference for new acquisitions of clostridium difficile, Methicillin-resistant Staphylococcus aureus and Extended Spectrum Beta Lactamase-positive (ESBL) Gram-negative coliforms when assessed up to 16 weeks. There was an OS benefit at 12 weeks (p=0.008) but not at one year (p=0.94). Interpretation: The addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths without increasing healthcare associated infections or carriage. Trial Registration Number: ISRCTN number: ISRCTN51731976 and EudraCT number: 2011-000366-35. Funding Statement: Funded by NIHR Health Technology Assessment Programme. 08/116/69. Declaration of Interests: None. Ethics Approval Statement: Approved by the UK Coventry & Warwickshire Multi-Research Ethics Committee on 29th July 2011. All patients provided written informed consent.