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

Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial
Information type: Randomised controlled trials
Source: The Lancet
Specialities: Cancers | Haematological disorders | Infection and infectious diseases
Summary
RCT (n=977) found addition of prophylactic levofloxacin to active myeloma treatment during first 12 weeks of therapy significantly reduced febrile episodes and deaths vs. placebo (HR 0.66, 95% CI 0·.51–0.86; p=0.0018) without increasing health care-associated infections.
UKMi comment
According to a commentary, the results of this trial provide a good basis for considering fixed-duration quinolone prophylaxis for newly diagnosed patients with myeloma starting therapy, but several questions/concerns remain:

• Although the primary endpoint of the study was met, there were no differences in overall survival at end of 1 year.

• The risk for infections remains higher during the overall treatment period compared with time not receiving chemotherapy. Therefore, the duration of antibiotic prophylaxis might need to be extended to cover the ongoing risk of infection.

Can the results be extrapolated to chemotherapy treatment combinations?

• Use of antibiotics could increase antibiotic resistance and induce gut dysbiosis.

It calls for further trials in this area, in particular, assessment of the therapeutic effects of a combination of co-trimoxazole and levofloxacin and investigation of various durations of antibiotic prophylaxis are crucial to optimise patient outcomes.

In March 2019, the MHRA imposed new restrictions and advised precautions on use of fluoroquinolone antibiotics due to very rare reports of disabling and potentially long-lasting or irreversible side effects affecting the musculoskeletal and nervous systems. Fluoroquinolone treatment should be discontinued at the first signs of a serious adverse reaction, including tendon pain or inflammation.
Related links: Comment MHRA warning