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Background: Myeloma causes profound immunodeficiency and recurrent, serious infections. Around 5500 new cases of myeloma are diagnosed per year in the UK, and a quarter of patients will have a serious infection within 3 months of diagnosis. We aimed to assess whether patients newly diagnosed with myeloma benefit from antibiotic prophylaxis to prevent infection, and to investigate the effect on antibiotic-resistant organism carriage and health care-associated infections in patients with newly diagnosed myeloma.Methods: TEAMM was a prospective, multicentre, double-blind, placebo-controlled randomised trial in patients aged 21 years and older with newly diagnosed myeloma in 93 UK hospitals. All enrolled patients were within 14 days of starting active myeloma treatment. We randomly assigned patients (1:1) to levofloxacin or placebo with a computerised minimisation algorithm. Allocation was stratified by centre, estimated glomerular filtration rate, and intention to proceed to high-dose chemotherapy with autologous stem cell transplantation. All investigators, patients, laboratory, and trial co-ordination staff were masked to the treatment allocation. Patients were given 500 mg of levofloxacin (two 250 mg tablets), orally once daily for 12 weeks, or placebo tablets (two tablets, orally once daily for 12 weeks), with dose reduction according to estimated glomerular filtration rate every 4 weeks. Follow-up visits occurred every 4 weeks up to week 16, and at 1 year. The primary outcome was time to first febrile episode or death from all causes within the first 12 weeks of trial treatment. All randomised patients were included in an intention-to-treat analysis of the primary endpoint. This study is registered with the ISRCTN registry, number ISRCTN51731976, and the EU Clinical Trials Register, number 2011-000366-35.Findings: Between Aug 15, 2012, and April 29, 2016, we enrolled and randomly assigned 977 patients to receive levofloxacin prophylaxis (489 patients) or placebo (488 patients). Median follow-up was 12 months (IQR 8-13). 95 (19%) first febrile episodes or deaths occurred in 489 patients in the levofloxacin group versus 134 (27%) in 488 patients in the placebo group (hazard ratio 0·66, 95% CI 0·51-0·86; p=0·0018. 597 serious adverse events were reported up to 16 weeks from the start of trial treatment (308 [52%] of which were in the levofloxacin group and 289 [48%] of which were in the placebo group). Serious adverse events were similar between the two groups except for five episodes (1%) of mostly reversible tendonitis in the levofloxacin group.Interpretation: Addition of prophylactic levofloxacin to active myeloma treatment during the first 12 weeks of therapy significantly reduced febrile episodes and deaths compared with placebo without increasing health care-associated infections. These results suggest that prophylactic levofloxacin could be used for patients with newly diagnosed myeloma undergoing anti-myeloma therapy.Funding: UK National Institute for Health Research. [ABSTRACT FROM AUTHOR]

Objectives: Patients with myeloma often face significant diagnostic delay, with up to one-third of UK patients diagnosed after an emergency presentation (EP). Compared with other routes, patients presenting as an emergency have more advanced disease, increased complications, and poorer prognosis., Methods: An economic model was developed using a decision-tree framework and lifetime time horizon to estimate costs related to different presentation routes (EP, general practitioner [GP] 2-week wait, GP urgent, GP routine, and consultant to consultant) for UK patients diagnosed as having myeloma. After diagnosis, patients received one of 3 first-line management options (observation, active treatment, or end-of-life care). Inputs were derived from UK health technology assessments and targeted literature reviews, or based on authors' clinical experience where data were unavailable. Active treatment, complication, and end-of-life care costs were included., Results: The average per-patient cost of treating myeloma (across all routes) was estimated at £146 261. The average per-patient cost associated with EP (£152 677) was the highest; differences were minimal compared with GP 2-week wait (£149 631) and consultant to consultant (£147 237). GP urgent (£140 025) and GP routine (£130 212) were associated with marginally lower costs. Complication (£42 252) and end-of-life care (£11 273) costs were numerically higher for EP than other routes (£25 021-£38 170 and £9772-£10 458, respectively)., Conclusions: An economic benefit may be associated with earlier diagnosis, gained via reduced complication and end-of-life care costs. Strategies to expedite myeloma diagnosis and minimize EPs have the potential to improve patient outcomes and may result in long-term savings that could offset any upfront costs associated with their implementation., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Multiple myeloma is a bone marrow cancer, which predominantly affects older people. The incidence is increasing in an ageing population.Over the last 10 years, patient outcomes have improved. However, this is less apparent in older, less fit patients, who are ineligible for stem cell transplant. Research is required in this patient group, taking into account frailty and aiming to improve: treatment tolerability, clinical outcomes and quality of life., Methods and Analysis: Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma is a national, phase III, multicentre, randomised controlled trial comparing standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide to lenalidomide+ixazomib, in patients with newly diagnosed multiple myeloma not suitable for stem cell transplant. Overall, 740 participants will be registered into the trial to allow 720 and 478 to be randomised at induction and maintenance, respectively.All participants will receive IRD induction with the dosing strategy randomised (1:1) at trial entry. Patients randomised to the standard, reactive arm will commence at the full dose followed by toxicity dependent reactive modifications. Patients randomised to the adaptive arm will commence at a dose level determined by their International Myeloma Working Group frailty score. Following 12 cycles of induction treatment, participants alive and progression free will undergo a second (double-blind) randomisation on a 1:1 basis to maintenance treatment with lenalidomide+placebo versus lenalidomide+ixazomib until disease progression or intolerance., Ethics and Dissemination: Ethical approval has been obtained from the North East-Tyne & Wear South Research Ethics Committee (19/NE/0125) and capacity and capability confirmed by local research and development departments for each participating centre prior to opening to recruitment. Participants are required to provide written informed consent prior to trial registration. Trial results will be disseminated by conference presentations and peer-reviewed publications., Trial Registration Number: ISRCTN17973108, NCT03720041., Competing Interests: Competing interests: ABC, K-LR, DAC, AH, CO, RH and PB report grants and non-financial support from BMS/Celgene, grants and non-financial support from Merck Sharpe & Dohme, grants and non-financial support from Amgen, grants and non-financial support from Takeda, during the conduct of the trial. DAC also reports travel support from Celgene Corporation. CPawlyn reports receiving honoraria and/or travel support from Amgen, BMS/Celgene, Janssen, Sanofi and Takeda. MK consultancy: AbbVie, Amgen, BMS/Celgene, GSK, Janssen, Karyopharm, Seattle Genetics, Takeda; honoraria: BMS/Celgene, Janssen, Takeda; Research funding: BMS/Celgene; Travel/educational support: BMS/Celgene, Janssen, Takeda. SB reports receiving research funding from Takeda. KB—Advisory Boards Janssen: BMS/Celgene, Takeda, Novartis. Speaker Honoraria: Janssen, BMS/Celgene, Sanofi, Takeda. Support to attend educational meetings: Janssen, BMS/Celgene, Takeda, GSK. GJ reports research funding from Takeda, Onyx, MSD & BMS/Celgene with consultancy from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche & BMS/Celgene. GC reports research funding from Janssen, Takeda, Amgen & BMS/Celgene with consultancy from Janssen, Takeda, Sanofi, Oncopeptides, Karyopharm, Pfizer, Roche & BMS/Celgene. MD reports Stock held in Abingdon Health. JB, RdT, NR, JJ, CParrish, HG, DM, BD, RO, MJ and BK have no declared competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)