A randomised placebo-controlled trial that aimed to tackle early morbidity and mortality in myeloma (TEAMM) revealed that prophylactic levofloxacin reduces the risk of infection and death in patients with myeloma.¹ The study was conducted in 93 hospitals throughout the United Kingdom.

Myeloma is a malignant disorder of plasma cells that causes various complications including anaemia, bone abnormalities, renal failure and immunodeficiency.² With immunodeficiency, the risk of infection in myeloma is greater in the first few months after diagnosis as the disease responds to an active treatment. Within this period, a third of myeloma patients were reported to contract serious infections that contribute to early mortality.^3–5 To address this, the TEAMM trial explored the protective impact of prophylactic antibiotic therapy in myeloma.

The study enrolled 977 patients who were randomly assigned to receive prophylactic levofloxacin (n=489) or placebo (n=488).¹ The patients in the levofloxacin group were given 500 mg of levofloxacin orally, once daily for 12 weeks with dose adjustments throughout the study based on their glomerular filtration rate. The primary outcome of the study was the time to the first febrile episode or death from all causes within the first 12 weeks of treatment. The number of febrile episodes, deaths and febrile episodes with death were assessed as secondary outcomes.

The study demonstrated that prophylactic levofloxacin significantly reduced the number of febrile episodes or deaths within 12 weeks of the treatment compared with placebo (95 versus 134 patients) with a hazard ratio for time to first event within 12 weeks of 0.66 (95% CI, 0·51–0·86; p=0·0018).¹ Cox regression analysis revealed that levofloxacin prophylaxis was the most important factor in reducing the number of febrile episodes or deaths.¹ Patients treated with prophylactic levofloxacin were also showed to have a lower number of febrile episodes (87 versus 112), deaths (4 versus 15) and febrile episodes with death (4 versus 7) within 12 weeks of treatment compared with those treated with placebo.

Levofloxacin was well-tolerated throughout the study, with similar serious adverse events rates reported between both the levofloxacin and placebo groups.¹ In addition, the perceived risk of health care-associated infections (HAI) secondary to antibiotic use was not evident in this study, with 40 cases of HAI in the levofloxacin group compared with 45 cases in the placebo group. However, prolonged antibiotic prophylaxis beyond 12 weeks requires further investigation.

Based on the findings from this study, the addition of a prophylactic levofloxacin regimen to an active myeloma treatment may be considered for newly diagnosed myeloma to reduce the risk of infection and early mortality. Further study should be pursued to explore any additional benefits of the regimen such as reduction of inflammation due to a change in microbiome as well as the efficacy and safety of antibiotic prophylaxis beyond 12 weeks which may keep a non-responder alive long enough for a second-line therapy.

References

1. Drayson MT, et al. The Lancet Oncology 2019;20:1760–1772.
2. Pratt G, et al. Br J Haematol 2007;138:563–579.
3. Augustson BM, et al. J Clin Oncol 2005;23:9219–9226.
4. Holmström MO, et al. Am J Hematol 2015;90:E73-74.
5. Public Health England. Cancer Data. Routes to Diagnosis 2006–2016 workbook. 2019. National Cancer registration and Analysis Service. Available at: https://www.cancerdata.nhs.uk/routestodiagnosis. Accessed 20 December 2019.