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Purpose: Romidepsin, a histone deacetylase inhibitor, has demonstrated activity in relapsed or refractory peripheral T-cell lymphoma (PTCL) as a single agent. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used as first-line treatment of PTCL; however, it has limited efficacy. Results from a phase Ib and II study showed the feasibility of combining romidepsin with CHOP (Ro-CHOP)., Methods: This study is a randomized phase III study of Ro-CHOP versus CHOP in adult patients with previously untreated PTCL. All patients received CHOP in 3-week cycles for six cycles. Romidepsin, 12 mg/m 2 , was administered intravenously over a 4-hour period on days 1 and 8 of each 3-week cycle for six cycles. The primary end point was progression-free survival (PFS) according to International Working Group 1999 criteria., Results: Between January 2013 and December 2017, 421 patients were enrolled (Ro-CHOP, n = 211; CHOP, n = 210). The median PFS for Ro-CHOP versus CHOP was 12.0 months (95% CI, 9.0 to 25.8) versus 10.2 months (95% CI, 7.4 to 13.2) with a hazard ratio of 0.81 ( P = .096). In the Ro-CHOP versus CHOP arms, the median overall survival was 51.8 versus 42.9 months and the objective response rate was 63% versus 60% with complete response plus unconfirmed complete response rates of 41% versus 37% ( P > .1 in all comparisons), respectively. Grade 3 or 4 treatment-emergent adverse events occurring in ≥ 30% of patients in the Ro-CHOP arm included thrombocytopenia (50% v 10% in the Ro-CHOP v CHOP arms, respectively), neutropenia (49% v 33%), anemia (47% v 17%), and leukopenia (32% v 20%)., Conclusion: The addition of romidepsin to CHOP did not improve PFS, response rates, nor overall survival and increased the frequency for grade ≥ 3 treatment-emergent adverse events. Ro-CHOP does not represent a significant advance in the standard of care for patients with previously untreated PTCL., Competing Interests: Emmanuel BachyHonoraria: Gilead Sciences, Roche, Amgen, Janssen-CilagConsulting or Advisory Role: Roche, Gilead Sciences, Incyte, TakedaResearch Funding: Amgen Foundation (Inst)Travel, Accommodations, Expenses: Janssen-Cilag, Roche, Gilead Sciences, Incyte Vincent CamusHonoraria: Roche/Genentech, Incyte, Janssen, Gilead Sciences, NovartisConsulting or Advisory Role: RocheResearch Funding: iQone Healthcare (Inst)Travel, Accommodations, Expenses: Pfizer, Roche Catherine ThieblemontHonoraria: Celgene, AbbVie, Bayer, Janssen, Roche, Incyte, Novartis, Gilead SciencesResearch Funding: RocheTravel, Accommodations, Expenses: Roche, Janssen-Cilag, Kite/Gilead, Novartis David SibonConsulting or Advisory Role: Takeda, iQone Healthcare, Janssen, Roche, AbbVieTravel, Accommodations, Expenses: Takeda, Janssen René-Olivier CasasnovasHonoraria: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, AmgenConsulting or Advisory Role: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, IncyteResearch Funding: Roche/Genentech (Inst), Gilead Sciences (Inst), Takeda (Inst)Travel, Accommodations, Expenses: Roche/Genentech, Takeda, Gilead Sciences, Janssen Loïc YsebaertHonoraria: AbbVieConsulting or Advisory Role: AbbVie, Janssen-Cilag, Roche, Gilead SciencesResearch Funding: Roche (Inst), Janssen-Cilag (Inst), Gilead Sciences (Inst) Gandhi DamajConsulting or Advisory Role: Roche/Genentech, Takeda, iQoneResearch Funding: TakedaTravel, Accommodations, Expenses: PFIZEE, Roche/Genentech, AbbVie Stéphanie GuidezConsulting or Advisory Role: Kite/GileadTravel, Accommodations, Expenses: Janssen Marc AndréConsulting or Advisory Role: Takeda, BMSiResearch Funding: Takeda (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, Celgene, Gilead Sciences Alejandro Martín García-SanchoHonoraria: Roche, Janssen-Cilag, Celgene, Servier, Gilead Sciences, TakedaConsulting or Advisory Role: Roche, Celgene, MorphoSys, Kyowa Hakko Kirin, iQone, EUSA Pharma, Gilead Sciences, Novartis, Servier, IncyteExpert Testimony: Gilead SciencesTravel, Accommodations, Expenses: Roche, Celgene¸ Servier Maria Jesus PenarrubiaHonoraria: AbbVie, Celgene, Servier, Takeda, RocheConsulting or Advisory Role: Gilead Sciences, Novartis, Celgene, AbbVie, Takeda, Clinigen GroupResearch Funding: CelgeneTravel, Accommodations, Expenses: Amgen, Servier, Novartis, Janssen, Celgene, Takeda Philipp B. StaberHonoraria: Roche, Amgen, Takeda, Abbott/AbbVie, Janssen Oncology, Incyte, Celgene, Bristol Myers Squibb/Pfizer, MSD Oncology, AstraZenecaResearch Funding: Roche (Inst) Judith TrotmanResearch Funding: BeiGene (Inst), Roche/Genentech (Inst), Pharmacyclics (Inst), Janssen-Cilag (Inst), Takeda (Inst), Celgene (Inst)Travel, Accommodations, Expenses: Roche/Genentech Andreas HüttmannHonoraria: TakedaConsulting or Advisory Role: TakedaTravel, Accommodations, Expenses: Roche Pharma AG Philippe GaulardHonoraria: Takeda, Gilead SciencesConsulting or Advisory Role: TakedaResearch Funding: Takeda (Inst), Innate Pharma (Inst), Sanofi (Inst)Travel, Accommodations, Expenses: Roche Marie-Helene Delfau-LarueHonoraria: Gilead Sciences, AmgenResearch Funding: Roche, CelgeneTravel, Accommodations, Expenses: Mundipharma Laurence de LevalHonoraria: Novartis (Inst)Consulting or Advisory Role: Lunaphore Technologies (Inst), Bayer (Inst) Michel MeignanHonoraria: RocheTravel, Accommodations, Expenses: Roche Ju LiEmployment: Bristol Myers Squibb/CelgeneStock and Other Ownership Interests: Bristol Myers Squibb/CelgeneResearch Funding: Bristol Myers Squibb/CelgeneTravel, Accommodations, Expenses: Bristol Myers Squibb/Celgene Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech Richard DelarueEmployment: Celgene/Bristol Myers Squibb, BeiGeneStock and Other Ownership Interests: Celgene/Bristol Myers Squibb, BeiGeneNo other potential conflicts of interest were reported.

Introduction: Apolipoprotein E (APOE) ε4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid β (Aβ) pathology., Methods: We included 3451 Aβ+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE ε4 prevalence in relation to age, sex, education, and geographical location., Results: The APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in Aβ+ cognitively normal and Aβ+ mild cognitive impairment (P < .05) but not in Aβ+ AD dementia (P = .66). The prevalence was highest in Northern Europe but did not vary by sex or education., Discussion: The APOE ε4 prevalence in AD was higher than that in previous studies, which did not require presence of Aβ pathology. Furthermore, our results highlight disease heterogeneity related to age and geographical location., (Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Background/aims: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia., Methods: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender., Results: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes 'hyperactivity', 'psychosis', 'affective symptoms' and 'apathy' across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively., Conclusion: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity., ((c) 2007 S. Karger AG, Basel.)

Background/aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer's disease (AD)., Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer's Disease Consortium were collected. Principal component analysis was used for factor analysis., Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients., Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD., ((c) 2007 S. Karger AG, Basel.)