Antibiotics Prevent Fevers, Death in Newly Diagnosed Myeloma Patients, Study Says

Antibiotics Prevent Fevers, Death in Newly Diagnosed Myeloma Patients, Study Says
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Preventive treatment with the antibiotic levofloxacin can lower the incidence of fever and death in people newly diagnosed with multiple myeloma, results from a Phase 3 clinical trial suggest.

The optimal length of time for treatment remains to be determined.

Results from the trial were published in The Lancet Oncology in a paper titled, “Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial.”

Both myeloma itself and the treatments used for it can weaken the immune system, which can increase the risk of developing infections. About a third of people with myeloma develop a serious bacterial infection within three months of being diagnosed.

While prophylactic (preventive) antibiotics could lower the incidence of infection, there are concerns about potential side effects and about increasing antibiotic resistance in bacteria.

The TEAMM Phase 3 clinical trial (ISRCTN51731976) included 977 people newly diagnosed with myeloma in the UK, with a median age 67. They were randomly assigned to treatment with either the antibiotic levofloxacin or a placebo, starting 14 days before standard-of-care treatment for myeloma.

The antibiotic dosage was 500 mg, taken orally every day for 12 weeks. Participants were followed for a median of one year.

During the trial period, 207 participants withdrew from the study  – 109 from the levofloxacin group and eight from the placebo group. The most commonly cited reasons for withdrawal were participant choice and suspected drug toxicity.

The high withdrawal rate “might reflect poor commitment of patients with newly diagnosed myeloma to a supportive care, placebo-controlled trial, possibly because they prioritize focusing on disease control,” the researchers said.

The trial’s primary goal was to determine the incidence of death from any cause or febrile (fever-causing) infections after 12 weeks. The incidence was significantly lower in the levofloxacin group, at just 95 patients (19%), compared with 134 (27%) of those on placebo.

There were 87 febrile infections in the levofloxacin group (18%), compared with 112 (23%) in the placebo group, and there were four (1%) and 15 (3%) total deaths in the respective groups. Incidence of febrile infections leading to death were four (1%) and seven (1%), respectively.

There were 29 serious adverse events in the levofloxacin group that were deemed at least possibly related to the study treatment, and 15 in the placebo group. There were five instances of tendinitis and one instance of delirium in the levofloxacin group, and none of either in the placebo group. Other adverse events, such as nausea, diarrhea, and anemia, occurred at comparable rates in both groups.

A total of 112 types of infectious agents were isolated during the study — 39% from the levofloaxacin group and 61% from the placebo group. These were mostly bacteria, though some viruses and fungi were also identified.

The bacteria were tested for their sensitivity to a range of different antibiotics. Similar rates of sensitivity were found in bacteria from the levofloxacin (70%) and placebo (73%) groups. Additionally, there were similar numbers of healthcare-associated infections in both groups (40 and 45, respectively).

“The perceived risks of increased carriage of antibiotic-resistant organisms and health care-associated infections were not evident in our study results,” the researchers said. That suggests “there might be situations when the use of prophylactic antibiotics does not increase the carriage of antibiotic-resistant organisms,” they said.

The levofloxacin group had a significantly higher survival rate after 12 weeks (98%, compared with 95% of the placebo group). However, after one year, there was no difference in survival between the two groups.

“A continuing infection risk beyond 12 weeks raises the question of whether the absence of survival benefit at 12 months might be due to early stopping of the intervention,” the researchers wrote, adding that extending the treatment to a full year “might be beneficial.”

“Investigation of various durations of antibiotic prophylaxis are crucial to optimize patient outcomes,” Karthik Ramasamy, PhD, FRCPath, lead myeloma clinician at Thames Valley Strategic Clinical Network, wrote in an editorial published alongside the study.

Extending antibiotic treatment requires thorough investigation, because it could have unintended consequences, Ramasamy said. For instance, he said, it’s probable that such antibiotic use could change the makeup of the bacteria that normally live in the body, which “has the potential to modify endogenous anti-tumor immunity and efficacy of immunotherapy in patients with myeloma.”

In addition, since antibiotics only kill bacteria, the best way to prevent other (e.g. viral) infections remains to be determined.

The “study is timely in showing that fixed-duration levofloxacin prophylaxis reduces febrile infections and early deaths in patients with myeloma during induction chemotherapy,” Ramasamy wrote,

Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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Inês holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she specialized in blood vessel biology, blood stem cells, and cancer. Before that, she studied Cell and Molecular Biology at Universidade Nova de Lisboa and worked as a research fellow at Faculdade de Ciências e Tecnologias and Instituto Gulbenkian de Ciência. Inês currently works as a Managing Science Editor, striving to deliver the latest scientific advances to patient communities in a clear and accurate manner.
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Marisa holds an MS in Cellular and Molecular Pathology from the University of Pittsburgh, where she studied novel genetic drivers of ovarian cancer. She specializes in cancer biology, immunology, and genetics. Marisa began working with BioNews in 2018, and has written about science and health for SelfHacked and the Genetics Society of America. She also writes/composes musicals and coaches the University of Pittsburgh fencing club.
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