The role of ixazomib as an augmented conditioning therapy in salvage autologous stem cell transplant (ASCT) and as a post-ASCT consolidation and maintenance strategy in patients with relapsed multiple myeloma (ACCoRd [UK-MRA Myeloma XII] trial): study protocol for a Phase III randomised controlled trial

Background: Multiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance. Methods/design: ACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively. All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression. Discussion: The question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Gut microbiome composition is associated with long-term disability worsening in multiple sclerosis

ABSTRACTPredicting the long-term outcome of multiple sclerosis (MS) remains an important challenge to this day. As the gut microbiota is emerging as a potential player in MS, we investigated in this study whether gut microbial composition at baseline is related to long-term disability worsening in a longitudinal cohort of 111 MS patients. Fecal samples and extensive host metadata were collected at baseline and 3 months post-baseline, with additional repeated neurological measurements performed over (median) 4.4 y. Worsening (with EDSS-Plus) occurred in 39/95 patients (outcome undetermined for 16 individuals). The inflammation-associated, dysbiotic Bacteroides 2 enterotype (Bact2) was detected at baseline in 43.6% of worsened patients, while only 16.1% of non-worsened patients harbored Bact2. This association was independent of identified confounders, and Bact2 was more strongly associated with EDSS-Plus than neurofilament light chain (NfL) plasma levels. Furthermore, using fecal sampling performed 3 months post-baseline, we observed Bact2 to be relatively stable, suggesting its potential use as a prognostic biomarker in MS clinical practice

The changing epidemiology of HIV in the criminal justice system.

Although the rate of HIV infection among US prison inmates is considerably higher than that of the general population, little is known about age-related changes in HIV-infected inmates over the last decade. This study of the nation's largest state prison system examined (1) whether the mean age of the HIV-infected inmate increased over the last decade, and (2) whether the prevalence of HIV and associated comorbidities varied according to age. The study population included all 230,103 inmates incarcerated in the Texas prison system for any duration during 2014. A separate analysis was conducted on all HIV-infected inmates incarcerated between 2004 and 2014. Information on medical conditions and demographic factors was obtained from an institution-wide electronic medical record system. From 2004 to 2014, the mean age of HIV-infected inmates in the prison system increased from 39.3 to 42.5 years, compared to an increase of 36.1-37.9 for all Texas prison inmates. Multivariable logistic regression was used to assess the independent contributions of multiple demographic and clinical covariates in predicting the binary outcome, HIV infection. The model showed that, in 2014, HIV infection was elevated in inmates who were aged 40-49 years (OR = 3.1; 95% CI 2.7-3.3), aged 50-59 years (OR = 2.4; 95% CI 2.1-2.7), African American (OR = 3.0; 95% CI 2.8-3.3), and in those with several chronic diseases, including chronic obstructive pulmonary disease (OR = 1.7; 95% CI 1.5-1.9), hepatitis C (OR = 2.7; 95% CI 2.5-3.1), major depressive disorder (OR = 1.7; 95% CI 1.5-2.1), bipolar disorder (OR = 2.3; 95% CI 1.8-2.8), and schizophrenia (OR = 1.5; 95% CI 1.3-1.8). Among HIV-infected inmates (n = 2960), the percentage with comorbid disease increased in a linear fashion according to age (p < .01). Correctional health systems must adapt to address the evolving epidemiology of HIV among inmate populations