Prophylactic antibiotics could benefit patients with newly diagnosed myeloma

Newly diagnosed patients with myeloma who are about to start treatment may benefit from a fixed course of prophylactic antibiotics to prevent Pneumocystis pneumonia, new research suggests.

The double-blind phase III randomised TEAMM trial of almost 1,000 newly diagnosed patients showed that a 12-week course of levofloxacin (500mg daily) during myeloma treatment reduced the incidence of febrile episodes and death compared to placebo (19% vs 27%; HR 0.66, 95% CI 0.51-0.86).

Overall survival at 12 weeks favoured the levofloxacin arm, with 98% of patients still alive compared with 95% in the placebo arm (P=0.0081) but there were no differences in overall survival at 12 months.

Patients who were given low co-trimoxazole to prevent Pneumocystis jirovecii infection had a lower risk of febrile episodes and death (HR 0.59). However, the authors noted that while this finding was ‘intriguing’ it should be interpreted with caution since co-trimoxazole use was unrandomised and determined by the treating centre.

“To our knowledge this is the first time that the use of prophylactic antibiotics has shown a survival benefit in patients with newly diagnosed myeloma,” the researchers led by Mark Drayson from the University of Birmingham in England wrote in their paper published in Lancet Oncology. 

They concluded that patients with newly diagnosed myeloma could benefit from levofloxacin prophylaxis, although local antibiotic resistance proportions must be considered.

In an accompanying editorial Karthik Ramasamy from the Oxford University Hospitals NHS Foundation Trust said the trial provided a good basis for considering fixed-duration quinolone prophylaxis in the studied patient population but questions remained.

For example, newer approaches to treatment often called for continuous therapy which might mean the duration of antibiotic prophylaxis would need to be extended to cover ongoing infection risk.

Patients in the trial were also treated primarily with immunomodulatory imide drug-based or proteasome inhibitor-based drug combinations, yet clinicians were moving towards monoclonal anti-body based drug combinations based on results from the ALCYONE and MAIA studies.

Grade 3 and grade 4 infections were higher in the daratumumab group than in the non-daratumumab group in both studies. Whether the results from Drayson and colleagues’ study can be extrapolated to chemotherapy treatment combinations is unclear. Moreover, it remains to be confirmed whether these results for newly diagnosed patients with myeloma can be generalised to patients with relapsed myeloma.

“Further trials are required 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,” he concluded.

Read the full study here