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Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.

Drayson, MT; Bowcock, S; Planche, T; Iqbal, G; Pratt, G; Yong, K; Wood, J; Raynes, K; Higgins, H; Dawkins, B; et al. Drayson, MT; Bowcock, S; Planche, T; Iqbal, G; Pratt, G; Yong, K; Wood, J; Raynes, K; Higgins, H; Dawkins, B; Meads, D; Hulme, CT; Monahan, I; Karunanithi, K; Dignum, H; Belsham, E; Neilson, J; Harrison, B; Lokare, A; Campbell, G; Hamblin, M; Hawkey, P; Whittaker, AC; Low, E; Dunn, JA; TEAMM Trial Management Group and Trial Investigators (2019) Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Oncol, 20 (12). pp. 1760-1772. ISSN 1474-5488 https://doi.org/10.1016/S1470-2045(19)30506-6
SGUL Authors: Planche, Timothy David

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Abstract

BACKGROUND: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma. METHODS: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35. FINDINGS: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group. INTERPRETATION: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy. FUNDING: UK National Institute for Health Research.

Item Type: Article
Additional Information: © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Keywords: TEAMM Trial Management Group and Trial Investigators, 1112 Oncology And Carcinogenesis, Oncology & Carcinogenesis
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Lancet Oncol
ISSN: 1474-5488
Language: eng
Dates:
DateEvent
December 2019Published
23 October 2019Published Online
26 June 2019Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
08/116/69National Institute for Health Researchhttp://dx.doi.org/10.13039/501100000272
PubMed ID: 31668592
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111362
Publisher's version: https://doi.org/10.1016/S1470-2045(19)30506-6

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