According to results from the phase 3 Tackling EArly Morbidity and Mortality in myeloma (TEAMM) trial (ISRCTN number: ISRCTN51731976; European Union Clinical Trials Register: 2011-000366-35), the addition of antibiotic prophylaxis via levofloxacin to the treatment regimen of patients with newly diagnosed myeloma decreases decreased febrile episodes and death compared with placebo. These study results were published in Lancet Oncology.
Myeloma results in severe immunodeficiency and recurrent, grave infections, with around 25% of patients experiencing a serious infection within 3 months of diagnosis.
TEAMM was a prospective, multicenter, double-blind, placebo-controlled randomized trial that involved 977 patients aged 21 years or older with newly diagnosed myeloma treated at 93 hospitals across the United Kingdom. Between August 2012 and April 2016, patients were randomized to prophylaxis with the antibiotic levofloxacin (489 patients) or to placebo (488 patients).
Patients received either 500 mg of oral levofloxacin once daily for 12 weeks or 500 mg of oral placebo once daily for 12 weeks. Doses were reduced per estimated glomerular filtration rate every 4 weeks. Follow-up occurred every 4 weeks for 16 weeks then again at 1 year.
With a median follow-up of 12 months (interquartile range, 8-13), 19% (95) of patients in the levofloxacin arm experienced first febrile episode or death vs 27% (134) of patients in the placebo arm (hazard ratio 0.66, 95% confidence interval, 0.51-0.86; P =.0018).
A total of 597 serious adverse events (AEs) occurred up to 16 weeks from the initiation of trial treatment, with 52% occurring in the levofloxacin arm and 48% in the placebo arm. Serious AEs were similar between the 2 treatment arms except for 5 episodes (1%) of primarily reversible tendonitis in the levofloxacin arm.
The results of the TEAMM trial suggest prophylactic levofloxacin could be used successfully to limit febrile episodes and death without increasing health care-associated infections in patients with newly diagnosed myeloma.
“Prolonged antibiotic prophylaxis after 12 weeks and combined antibiotic use for prophylaxis requires investigation in future studies,” noted the authors.
Drayson MT, Bowcock S, Planche T, et al. Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial [published online October 23, 2019]. Lancet Oncol. doi:10.1016/S1470-2045(19)30506-6