Rationale:

Myeloma is a cancer of bone marrow plasma cells that causes profound immunosuppression. There is a high early death rate with the biggest single cause being infection. Recent improvements in overall survival in myeloma mean that prevention of early death has become more pressing, especially as early death affects all prognosis groups.

Antibiotic prophylaxis is likely to be the single most effective measure to prevent early death in myeloma. Treatment with antibiotics once an infection is established is probably not sufficient, as the early death rate in older patients remained constant over a 20 year period despite improvements in supportive care. The use of antibiotic prophylaxis is evidence based established practice in some areas of medicine, e.g. neutropenia, HIV, but the recent rise in healthcare associated infections (HCAI) has raised concern about the risks of antibiotic prophylaxis. Although the benefits are well established, there is concern that clinicians are withholding antibiotic prophylaxis because of fears of HCAI. Extrapolating from current data the benefits of prophylaxis are likely to outweigh the risks of HCAI. However there has not been a large trial looking at the benefits of antibiotic prophylaxis versus the risks of HCAI. Examination of the organisms causing infection in myeloma suggests that Levofloxacin, given for the first 12 weeks, is the best antibiotic for prophylaxis.

Reducing infection in the first 3 months may increase the myeloma response rate primarily by reducing the number of interruptions of anti-myeloma therapy. There is also some evidence for a role for infections driving myeloma pathogenesis directly although further proof is required to confirm this effect in vivo.

 

Eligibility:

• Age ≥ 21 years and able to give informed consent

• Patient with newly diagnosed symptomatic myeloma based on internationally agreed criteria

• There is an intention to treat the patient’s myeloma actively

• Patient is no more than 14 days prior to or no more than 14 days into starting a programme of anti-myeloma therapy Provision of written informed consent

   

Treatment:

Experimental arm: Levofloxacin 500 mg once daily orally for 12 weeks.

Control Arm: Placebo once daily orally for 12 weeks.

All patients will receive Anti-myeloma therapy.

 

Hypotheses:

Levofloxacin used once daily as anti-bacterial prophylaxis in newly diagnosed symptomatic myeloma will:-

1) Reduce the rate of febrile episodes, hospitalisation, and death

2) Increase response to anti-myeloma therapy

3) Improve quality of life and overall survival

The trial will also test if levofloxacin affects the carriage of and invasive infection by three important groups of bacteria; C. difficile, S. aureus (including MRSA) and ESBL coliforms.

1) Is the carriage of these organisms increased in patients receiving levofloxacin compared to those receiving placebo?

2) Is the carriage of these organisms associated with later invasive infections?

Does levofloxacin increase the rate of invasive infections by these three groups of organisms?

 

Number of patients:

977

 

Sample Collection:

At entry, 4, 8, 12 & 16 weeks central laboratory analysis of stools and nasal swabs for microbiology; blood and urine for paraprotein response and immune function

 

Sub-Studies:

Quality of Life - EQ-5D, EORTC-QLQ C30 and HADs (Hospital Anxiety & Depression scale)