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  • 1
    In: Genetics in Medicine, Elsevier BV, Vol. 25, No. 4 ( 2023-04), p. 100006-
    Type of Medium: Online Resource
    ISSN: 1098-3600
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Elsevier BV ; 2002
    In:  Journal of Investigative Dermatology Vol. 119, No. 2 ( 2002-08), p. 535-538
    In: Journal of Investigative Dermatology, Elsevier BV, Vol. 119, No. 2 ( 2002-08), p. 535-538
    Type of Medium: Online Resource
    ISSN: 0022-202X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2002
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  • 3
    Online Resource
    Online Resource
    California Digital Library (CDL) ; 2001
    In:  Dermatology Online Journal Vol. 7, No. 1 ( 2001-03-01)
    In: Dermatology Online Journal, California Digital Library (CDL), Vol. 7, No. 1 ( 2001-03-01)
    Type of Medium: Online Resource
    ISSN: 1087-2108
    Language: Unknown
    Publisher: California Digital Library (CDL)
    Publication Date: 2001
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  • 4
    In: Dermatologic Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 4, Part 2 ( 2004-04), p. 598-603
    Type of Medium: Online Resource
    ISSN: 1076-0512
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 2020062-6
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  • 5
    In: Dermatologic Surgery, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 4p2 ( 2004-04), p. 598-603
    Type of Medium: Online Resource
    ISSN: 1076-0512 , 1524-4725
    URL: Issue
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2004
    detail.hit.zdb_id: 2020062-6
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  • 6
    In: Brain Stimulation, Elsevier BV, Vol. 7, No. 4 ( 2014-07), p. 620-622
    Type of Medium: Online Resource
    ISSN: 1935-861X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2014
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  • 7
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 2582-2582
    Abstract: Background: Vorinostat is a histone deacetylase inhibitor that has been approved by the US FDA for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following 2 prior therapies. Patients and Methods: A Phase IIb, open-label trial of oral vorinostat 400 mg daily until progressive disease (PD) or intolerable toxicity was conducted in patients with advanced CTCL. Patients must have received at least 2 prior therapies and recovered from all prior treatment-related toxicities. The primary end point was the objective response rate in patients with stage IIB or higher CTCL as measured by the severity weighted assessment tool. Time to response (TTR), duration of response (DOR), pruritus relief, safety, and tolerability were also evaluated. Patients who had received vorinostat therapy for at least 2 years as of August 1, 2007 were further evaluated in this post-hoc subset analysis. Results: Six of 74 patients originally treated in the study have received vorinostat therapy for at least 2 years as of 8/1/07, including 5 responders (1 complete responder, 4 partial responders) and 1 with prolonged stable disease (Figure 1). The median age was 65 years (range, 57–74), the median number of prior systemic therapies was 2.5 (range, 1–5), and the median time from CTCL diagnosis to enrollment was 1.8 years (range, 0–5.9). The most common drug-related adverse experiences were diarrhea (100%), fatigue (67%), nausea (50%), and alopecia (50%). Grade ≥ 3 drug-related adverse experiences were anorexia (n = 1), pulmonary embolism (PE, n = 1), and thrombocytopenia (n = 1). The PE (Day 144) was a serious adverse experience (SAE) that resolved within 7 days, and this patient is continuing on therapy as of Day 848. The only other SAE was a rash (Day 925). Two patients discontinued due to PD and 4 are continuing on therapy as of August 1, 2007. Conclusions: Vorinostat has demonstrated prolonged safety and clinical benefit in patients with advanced CTCL. Figure 1. Time on study of patients on vorinostat therapy for ≥ 2 years (available data as of August 1, 2007). Figure 1. Time on study of patients on vorinostat therapy for ≥ 2 years (available data as of August 1, 2007).
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 8
    In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2903-2903
    Abstract: Background: Cobomarsen (MRG-106) is an inhibitor of miR-155, a microRNA with a strong link to cutaneous T cell lymphoma (CTCL) pathogenesis. The goals of this first in human study are to evaluate the safety, tolerability, pharmacokinetics, and efficacy of cobomarsen in mycosis fungoides (MF) patients. Methods: This Phase 1 trial evaluated cobomarsen given via intralesional injection (75 mg/dose), subcutaneous (SC), IV rapid bolus injection, or 2-hour IV infusion (300, 600 or 900 mg/dose). Patients must have MF stage I-III with plaques and/or tumors and could remain on concurrent stable CTCL therapy. Patients received 6 doses, either subcutaneous or intravenous, in the first 26 days of the study followed by weekly or bi-monthly doses. Safety was monitored by physical exams, clinical lab tests, and reported adverse events (AEs). Efficacy was assessed by CAILS and by the modified Severity Weighted Assessment Tool (mSWAT). The effect of cobomarsen on quality of life was assessed by Skindex-29. Results: 38 subjects receiving IV or SC treatment (25 male/13 female, median age 59 years) have been on study for up to 22 months. As of the data cut off, no serious AEs have been attributed to cobomarsen. The most common AEs reported in greater than 15% of subjects were: fatigue, neutropenia, injection site pain, nausea, pruritus, and headache. Two AEs were deemed dose limiting toxicities (DLTs): Grade 3 worsening pruritus and Grade 3 tumor flare. The maximum tolerated dose (MTD) has not yet been reached. In the subcutaneous and IV cohorts, 29 out of 32 (91%) evaluable subjects had improvement in mSWAT score. Skin improvements were observed as early as the first assessment (Day 17). The best improvements were observed after more than 1 month of treatment. Eleven out of twenty-one (52%) patients receiving more than one month of dosing (6 doses) achieved greater than 50% reduction in mSWAT score. The mean duration of response (n=11) was 213 days, as of data cut off. Eight patients achieved a partial response meeting the criteria for ORR4, an objective response rate lasting at least four months in duration. The overall skin response in patients who received cobomarsen as monotherapy or cobomarsen with concurrent stable therapy were not significantly different. Improvement in quality of life (QOL), as measured by the Skindex-29 total score, correlated with reductions in mSWAT score during the treatment phase. Conclusions: These results demonstrate that cobomarsen is well-tolerated, has clinical activity, and has the potential to impact MF quality of life. These encouraging data support the continued investigation of cobomarsen in the CTCL population. The study is expanded to enroll patients with other hematologic malignancies in which miR-155 is elevated and relevant, including chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), and adult T cell lymphoma/leukemia (ATLL). Final safety and efficacy data on CTCL mycosis fungoides will be presented. Disclosures Foss: Seattle genetics: Consultancy; Miragen: Consultancy, Speakers Bureau; Spectrum: Consultancy; Mallinkrodt: Consultancy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2018
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  • 9
    In: Blood, American Society of Hematology, Vol. 114, No. 22 ( 2009-11-20), p. 1709-1709
    Abstract: Abstract 1709 Poster Board I-735 Background Vorinostat (Zolinza®) is an oral histone deacetylase inhibitor licensed by the United States Food and Drug Administration for the treatment of cutaneous manifestations of CTCL in pts with progressive and persistent disease on or following two prior systemic therapies. In a pivotal Phase IIB, open-label, multicenter trial in pts with advanced CTCL, vorinostat was well tolerated and associated with an overall response rate of 29.7% and a 29.5% response rate in pts with ≥Stage IIB disease. CTCL pts with a high blood tumor burden have a poorer prognosis and treatment of these pts represents an unmet medical need. Aim This post hoc analysis of the pivotal trial of vorinostat in CTCL assesses its potential effectiveness in treating systemic disease in pts with high blood tumor burden. Methods Pts with advanced CTCL received oral vorinostat 400 mg daily until disease progression or intolerable toxicity. Eligible pts had received ≥2 prior systemic therapies that included bexarotene unless intolerable. Pts were characterized as having a high blood tumor burden if at baseline they had counts of CD4+/CD26- cells 〉 1000 per μL by flow, and additionally, Sézary syndrome (SS) pts were also required to have 〉 80% erythroderma at the time of study entry. The tumor response in the blood and skin were examined. An objective blood response was defined as a ≥50% decrease in blood tumor burden and progression as a ≥25% increase from baseline. An objective response in the skin was defined as ≥50% reduction in mSWAT score from baseline assessment. Results Of 74 pts who entered the trial, 18 of 19 had a high blood tumor burden and were evaluable for this analysis. Of these 18, SS was present in 11 pts. Overall, an objective blood response was observed in 28% (5/18) of pts and an objective skin response in 44% (8/18) pts. An objective response in both blood and skin was observed in 17% (3/18) pts. The median change in blood tumor burden for all 11 SS pts was a 35% decrease (range: 23% increase - 94% decrease). An objective response in both the blood and skin was observed in 1 pt with SS who had a 76% decrease in CD4+/CD26- cells and a 99% reduction in mSWAT scores with a time to response of 115 and 28 days, respectively. An objective response in the blood alone was observed in 18% (2/11) of pts with SS with a decrease of 51% and 94% CD4+/CD26- cells and a time to response of 43 and 114 days, respectively. The skin response in these pts was a 30% and 17% reduction in mSWAT scores with a time to response of 28 and 142 days, respectively. Three of the 11 pts (27%) with SS had an objective response in the skin alone with changes in mSWAT score of 51%, 53%, and 58%, and a time to response of 28, 87, and 142 days, respectively. The changes in blood tumor burden in these pts were −35%, −13%, and +23%. The median change in blood tumor burden for the 7 pts not meeting criteria for SS was a 39% decrease (1 pt with a 327% increase and 6 pts with 6%-62% decrease). For these pts not meeting criteria for SS, an objective blood response was observed in 29% (2/7) pts and each of these pts had an objective skin response with a 50% and 62% decrease in CD4+/CD26- cells and a 63% and 67% reduction in mSWAT scores, respectively. The time to blood response was 233 and 205 days and to skin response was 114 and 171 days, respectively. An objective response in the skin alone was observed in 43% (3/7) non-SS pts with decreases in mSWAT score ranging from 61%-81% with a time to response of 29-85 days. The changes in blood tumor burden for these 3 pts were −49%, −24%, and +327%. Conclusion These results demonstrate the potential effectiveness of vorinostat in reducing not only the skin but the blood tumor burden in pts with CTCL and SS. Further study in prospective clinical trials is necessary to expand on these findings. Disclosures Duvic: Merck: Honoraria, Research Funding, Speakers Bureau. Kim:Merck: Membership on an entity's Board of Directors or advisory committees; Eisai: Membership on an entity's Board of Directors or advisory committees. Kuzel:Merck: Membership on an entity's Board of Directors or advisory committees. Pacheco:Merck: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Foss:Gloucester: Consultancy; Eisai: Consultancy; Merck: Consultancy; Allos: Consultancy. Rizvi:Merck: Employment, Equity Ownership. Chen:Merck: Employment, Equity Ownership. Arduino:Merck: Employment, Equity Ownership. Olsen:Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2009
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  • 10
    In: Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. Suppl 2 ( 2021-11), p. A838-A839
    Abstract: Immune checkpoint inhibitors (ICIs) are a pillar of cancer therapy with demonstrated efficacy in a variety of malignancies. However, they are associated with immune-related adverse events (irAEs) that affect many organ systems with varying severity, inhibiting patient quality of life and in some cases the ability to continue immunotherapy. Research into irAEs is nascent, and identifying patients with adverse events poses a critical challenge for future research efforts and patient care. This study's objective was to develop an electronic health record (EHR)-based model to identify and characterize patients with ICI-associated arthritis (checkpoint arthritis). Methods Forty-two patients with checkpoint arthritis were chart abstracted from a cohort of all patients who received checkpoint therapy for cancer (n=2,612) in a single-center retrospective study. All EHR clinical codes (N=32,198) were extracted including International Classification of Diseases (ICD)-9 and ICD-10, Logical Observation Identifiers Names and Codes (LOINC), RxNorm, and Current Procedural Terminology (CPT). Logistic regression, random forest, gradient boosting, support vector machine, K-nearest neighbors, and neural network machine learning models were trained to identify checkpoint arthritis patients using these clinical codes. Models were evaluated using receiver operating characteristic area under the curve (ROC-AUC), and the most important variables were determined from the logistic regression model. Models were retrained on smaller fractions of the important variables to determine the minimum variable set necessary to achieve accurate identification of checkpoint arthritis. Results Logistic regression and random forest were the highest performing models on the full variable set of 32,198 clinical codes (AUCs: 0.911, 0.894, respectively) (table 1). Retraining the models on smaller fractions of the most important variables demonstrated peak performance using the top 31 clinical codes, or 0.1% of the total variables (figure 1). The most important features included presence of ESR, CRP, rheumatoid factor lab, prednisone, joint pain, creatine kinase lab, thyroid labs, and immunization, all positively associated with checkpoint arthritis (figure 2). Conclusions Our study demonstrates that a data-driven, EHR based approach can robustly identify checkpoint arthritis patients. The high performance of the models using only the 0.1% most important variables suggests that only a small number of clinical attributes are needed to identify these patients. The variables most important for identifying checkpoint arthritis included several unexpected clinical features, such as thyroid labs and immunization, indicating potential underlying irAE associations that warrant further exploration. Finally, the flexibility of this approach and its demonstrated effectiveness could be applied to identify and characterize other irAEs. Ethics Approval This study was approved by the Northwestern University Institutional Review Board, ID STU00210502, with a granted waiver of consent Abstract 802 Table 1 Model performance metrics AUC was calculated from the ROC curve. Sensitivity, specificity, PPV, and NPV were determined at the threshold maximizing the F1-score. AUC = area under the curve, ROC = receiver operating characteristic, PPV = positive predictive value, NPV = negative predictive value Abstract 802 Figure 1 Model AUC trained on decreasing fractions of the most important variables, determined by the random forest model. 100% = 32,198 clinical codes. LReg = logistic regression, RF = random forest, GB = gradient boosting, NN = neural network, KNN = K-nearest neighbor, SVM = support vector machine, SVMAnom = SVM anomaly detection Abstract 802 Figure 2 The 31 most important variables determined by the logistic regression (A, coefficients) and random forest (B, relative importance) models
    Type of Medium: Online Resource
    ISSN: 2051-1426
    Language: English
    Publisher: BMJ
    Publication Date: 2021
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