Prophylactic levofloxacin to prevent infections in newly diagnosed symptomatic myeloma: the TEAMM RCT.

BACKGROUND

Myeloma causes profound immunodeficiency and recurrent serious infections. There are approximately 5500 new UK cases of myeloma per annum, and one-quarter of patients will have a serious infection within 3 months of diagnosis. Newly diagnosed patients may benefit from antibiotic prophylaxis to prevent infection. However, the use of prophylaxis has not been established in myeloma and may be associated with health-care-associated infections (HCAIs), such as

OBJECTIVES

To assess the risks, benefits and cost-effectiveness of prophylactic levofloxacin in newly diagnosed symptomatic myeloma patients.

DESIGN

Multicentre, randomised, double-blind, placebo-controlled trial. A central telephone randomisation service used a minimisation computer algorithm to allocate treatments in a 1 : 1 ratio.

SETTING

A total of 93 NHS hospitals throughout England, Northern Ireland and Wales.

PARTICIPANTS

A total of 977 patients with newly diagnosed symptomatic myeloma.

INTERVENTION

Patients were randomised to receive levofloxacin or placebo tablets for 12 weeks at the start of antimyeloma treatment. Treatment allocation was blinded and balanced by centre, estimated glomerular filtration rate and intention to give high-dose chemotherapy with autologous stem cell transplantation. Follow-up was at 4-week intervals up to 16 weeks, with a further follow-up at 1 year.

MAIN OUTCOME MEASURES

The primary outcome was to assess the number of febrile episodes (or deaths) in the first 12 weeks from randomisation. Secondary outcomes included number of deaths and infection-related deaths, days in hospital, carriage and invasive infections, response to antimyeloma treatment and its relation to infection, quality of life and overall survival within the first 12 weeks and beyond.

RESULTS

In total, 977 patients were randomised (levofloxacin,

LIMITATIONS

Short duration of prophylactic antibiotics and cost-effectiveness.

CONCLUSIONS

During the 12 weeks from new diagnosis, the addition of prophylactic levofloxacin to active myeloma treatment significantly reduced febrile episodes and deaths without increasing HCAIs or carriage. Future work should aim to establish the optimal duration of antibiotic prophylaxis and should involve the laboratory investigation of immunity, inflammation and disease activity on stored samples funded by the TEAMM (Tackling Early Morbidity and Mortality in Myeloma) National Institute for Health Research Efficacy and Mechanism Evaluation grant (reference number 14/24/04).

TRIAL REGISTRATION

Current Controlled Trials ISRCTN51731976.

FUNDING DETAILS

This project was funded by the NIHR Health Technology Assessment programme and will be published in full in

WHAT IS THE PROBLEM?

Myeloma is a type of cancer that develops from cells in the bone marrow, called plasma cells, which are part of the immune system. Because myeloma affects the immune system, people who have it are at greater risk of picking up infections. This risk is higher at the start of antimyeloma therapy when the myeloma is active.

WHAT DID THE STUDY DO?

The trial looked to see if the risk of getting an infection can be reduced, rather than waiting to see if an infection developed and then treating it. An antibiotic already used all over the world, called levofloxacin was tested. Half of the patients (

WHAT DID THE STUDY FIND?

During the 12 weeks from new diagnosis of myeloma, the addition of prophylactic levofloxacin to active myeloma treatment significantly reduced the number of febrile episodes and deaths [134 (febrile episodes alone,

Déclaration de conflit d'intérêts

Mark T Drayson reports personal fees from Abingdon Health (Abingdon Health, York, UK) outside the submitted work. Stella Bowcock reports personal fees from Amgen (Amgen, CA, USA) and Celgene (Celgene, NJ, USA) outside the submitted work, non-financial support to attend educational meetings and has a patent issued for a device broadly related to the work. Tim Planche reports personal fees from Pfizer (Pfizer, CT, USA), Actellion (Actellion, Allschnil, Switzerland) and Astellas (Astellas Pharma, Tokyo, Japan) outside the submitted work. Kwee Yong reports grants from Janssen (Janssen Pharmaceutica, Beerse, Belgium), Celgene and Chugai (Chugai Pharmaceutical Co Tokyo, Japan) outside the submitted work. David Meads is a member of the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) European Economic and Social Committee (EESC) Methods Group and the NIHR HTA EESC Panel. Claire T Hulme is a member of the NIHR HTA Commissioning Board. Janet A Dunn is a member of the NIHR Efficacy and Mechanism Evaluation board.