Preferences for Accessing Patient Reported Outcomes and Health Information Among Thrombotic Thrombocytopenic Purpura Survivors

Abstract Introduction: Our previous qualitative studies of immune-mediated thrombotic thrombocytopenic purpura (iTTP) survivors revealed that patients did not communicate to their hematologists about residual cognitive and fatigue issues. A way to overcome this communication barrier is implementation of patient-reported outcomes (PROs) in routine care. Integration of PROs into the clinical care of other diseases has resulted in improved patient-provider communication, symptom management, quality of life and overall patient satisfaction. However, decisions about the mode of administration are challenging. Although 92% of the United States population has access to the internet, studies have shown minorities prefer alternative modes of administration. Given that iTTP disproportionately affects Black women, understanding patient preference is critical for integrating PRO instruments into routine care. The primary study goal was to determine the preferred mode of administration of PRO instruments in iTTP. Furthermore, many individuals use the internet as a source of medical information/advice. A study of iTTP literacy reported that only 34% of survivors correctly identified disease relapse risk factors suggesting a critical knowledge gap. A secondary goal was to describe iTTP survivors' behaviors regarding using the internet for medical information or support. Methods: We utilized a cross-sectional study design. iTTP survivors were recruited from August 2019 until present. Eligibility included: 1) age >18 years, 2) documented ADAMTS13 deficiency (< 10% activity) at diagnosis or during a relapse and 3) > 1-year clinical remission. Multi-center recruitment of survivors included: Oklahoma University, Ohio State University, University of Minnesota, Johns Hopkins University, University of Rochester, University of Pennsylvania, University of Alabama at Birmingham, University of Utah and the University of Vermont. Following informed consent, survivors were administered the PROMIS ® cognitive function ability, anxiety and fatigue instruments via their preferred mode (online, telephone, or self-administered). Typical internet usage, behaviors regarding searching for health information online and demographics were also obtained. Results: To date, 94 survivors have completed the study (83% female; 54% White; 34% Black; median age 49 years [range 26-85 years]). A majority (54%) preferred completing PROMIS ® surveys online vs. self-administered or telephone administered. However, among Black survivors, only 38% preferred online administration and among survivors aged ≥65 years only 22% preferred online administration. Interestingly, there was an overall shift in a preference toward online administration following the onset of the COVID-19 pandemic (45% (21/47) preferred online pre vs 66% (31/47) preferred online post). Ninety-one percent (86/94) of survivors reported at least occasional internet use vs 8 (9%) reported none. Similarly, 82% (70/85) had searched the internet for health/medical information for themselves in the past year. Also 62% (53/86) of the survivors selected 'strongly agree' or 'agree' to the statement that the internet helps them determine if symptoms are important enough to see a doctor. Likewise, 62% used the internet to interpret doctor's recommendations. Additionally, 47% (40/86) 'strongly agree/agree' the internet helped determine if they would take a medication/seek alternative treatment. Moreover, 64% (55/86) agreed the internet was a good way to find others experiencing similar health problems. However, when asked about behaviors over the past year, only 42% (36/85) used online social networking sites like Facebook to look for health information or find others with iTTP and only 36% (31/85) had actually participated in online iTTP support groups. Conclusions: Overall iTTP survivors preferred online PRO administration; however, Black and older survivors preferred other methods. Recognizing these preferences is a vital step toward integrating PROs into routine care. Furthermore, iTTP survivors are using the internet as a source of medical support and information. Therefore, it is critical to not only educate iTTP survivors about credible online resources but also to create additional content. Also, future studies are needed to further explore the impact of the COVID-19 pandemic on online health behaviors. Disclosures Terrell: Sanofi: Consultancy; Takeda: Consultancy. Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Mazepa: Answering TTP Foundation: Research Funding; Sanofi Aventis: Other. Cuker: Spark Therapeutics: Research Funding; Sanofi: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Novo Nordisk: Research Funding; Novartis: Research Funding; Bayer: Research Funding; Alexion: Research Funding; UpToDate: Patents & Royalties; Synergy: Consultancy. Chaturvedi: Dova: Other: Advisory board member; UCB: Other: Advisory board participation; Argenx: Other: Advisory board member; Alexion: Other: Advisory board member; Sanofi Genzyme: Other: Advisory board member. Lim: Hema Biologics: Honoraria; Sanofi Genzyme: Honoraria; Dova Pharmaceuticals: Honoraria. Gangaraju: Alexion: Consultancy; Sanofi Genzyme: Consultancy. Cataland: Alexion: Consultancy, Research Funding; Sanofi Genzyme: Consultancy; Ablynx/Sanofi: Consultancy, Research Funding; Takeda: Consultancy.

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Cancer patients’ information seeking behavior related to online electronic healthcare records

Health Informatics Journal ◽

10.1177/14604582211024708 ◽

2021 ◽

Vol 27 (3) ◽

pp. 146045822110247

Author(s):

Hanife Rexhepi ◽

Isto Huvila ◽

Rose-Mharie Åhlfeldt ◽

Åsa Cajander

Keyword(s):

Cancer Patients ◽

Health Information ◽

Information Seeking ◽

Healthcare Professionals ◽

Medical Information ◽

Information Seeking Behavior ◽

The Internet ◽

Seeking Behavior ◽

Information Horizons ◽

Health Information Sources

Patients’ online access to their EHR together with the rapid proliferation of medical information on the Internet has changed how patients use information to learn about their health. Patients’ tendency to turn to the Internet to find information about their health and care is well-documented. However, little is known about patients’ information seeking behavior when using online EHRs. By using information horizons as an analytical tool this paper aims to investigate the information behavior of cancer patients who have chosen to view their EHRs (readers) and to those who have not made that option (non-readers). Thirty interviews were conducted with patients. Based on information horizons, it seems that non-reading is associated with living in a narrower information world in comparison to readers. The findings do not suggest that the smallness would be a result of active avoidance of information, or that it would be counterproductive for the patients. The findings suggest, however, that EHRs would benefit from comprehensive linking to authoritative health information sources to help users to understand their contents. In parallel, healthcare professionals should be more aware of their personal role as a key source of health information to those who choose not to read their EHRs.

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Combination of NKTR-255, a Polymer Conjugated Human IL-15, with CD19 CAR T Cell Immunotherapy in a Preclinical Lymphoma Model

Blood ◽

10.1182/blood-2019-125960 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2866-2866 ◽

Cited By ~ 2

Author(s):

Cassie Chou ◽

Simon Fraessle ◽

Rachel Steinmetz ◽

Reed M. Hawkins ◽

Tinh-Doan Phi ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Research Funding ◽

Board Member ◽

Ad Hoc ◽

Advisory Board ◽

Car T Cells ◽

Car T Cell ◽

Car T ◽

Equity Ownership

Background CD19 CAR T immunotherapy has been successful in achieving durable remissions in some patients with relapsed/refractory B cell lymphomas, but disease progression and loss of CAR T cell persistence remains problematic. Interleukin 15 (IL-15) is known to support T cell proliferation and survival, and therefore may enhance CAR T cell efficacy, however, utilizing native IL-15 is challenging due to its short half-life and poor tolerability in the clinical setting. NKTR-255 is a polymer-conjugated IL-15 that retains binding affinity to IL15Rα and exhibits reduced clearance, providing sustained pharmacodynamic responses. We investigated the effects of NKTR-255 on human CD19 CAR T cells both in vitro and in an in vivo xenogeneic B cell lymphoma model and found improved survival of lymphoma bearing mice receiving NKTR-255 and CAR T cells compared to CAR T cells alone. Here, we extend upon these findings to further characterize CAR T cells in vivo and examine potential mechanisms underlying improved anti-tumor efficacy. Methods CD19 CAR T cells incorporating 4-1BB co-stimulation were generated from CD8 and CD4 T cells isolated from healthy donors. For in vitro studies, CAR T cells were incubated with NKTR-255 or native IL-15 with and without CD19 antigen. STAT5 phosphorylation, CAR T cell phenotype and CFSE dilution were assessed by flow cytometry and cytokine production by Luminex. For in vivo studies, NSG mice received 5x105 Raji lymphoma cells IV on day (D)-7 and a subtherapeutic dose (0.8x106) of CAR T cells (1:1 CD4:CD8) on D0. To determine optimal start date of NKTR-255, mice were treated weekly starting on D-1, 7, or 14 post CAR T cell infusion. Tumors were assessed by bioluminescence imaging. Tumor-free mice were re-challenged with Raji cells. For necropsy studies mice received NKTR-255 every 7 days following CAR T cell infusion and were euthanized at various timepoints post CAR T cell infusion. Results Treatment of CD8 and CD4 CAR T cells in vitro with NKTR-255 resulted in dose dependent STAT5 phosphorylation and antigen independent proliferation. Co-culture of CD8 CAR T cells with CD19 positive targets and NKTR-255 led to enhanced proliferation, expansion and TNFα and IFNγ production, particularly at lower effector to target ratios. Further studies showed that treatment of CD8 CAR T cells with NKTR-255 led to decreased expression of activated caspase 3 and increased expression of bcl-2. In Raji lymphoma bearing NSG mice, administration of NKTR-255 in combination with CAR T cells increased peak CAR T cell numbers, Ki-67 expression and persistence in the bone marrow compared to mice receiving CAR T cells alone. There was a higher percentage of EMRA like (CD45RA+CCR7-) CD4 and CD8 CAR T cells in NKTR-255 treated mice compared to mice treated with CAR T cells alone and persistent CAR T cells in mice treated with NKTR-255 were able to reject re-challenge of Raji tumor cells. Additionally, starting NKTR-255 on D7 post T cell infusion resulted in superior tumor control and survival compared to starting NKTR-255 on D-1 or D14. Conclusion Administration of NKTR-255 in combination with CD19 CAR T cells leads to improved anti-tumor efficacy making NKTR-255 an attractive candidate for enhancing CAR T cell therapy in the clinic. Disclosures Chou: Nektar Therapeutics: Other: Travel grant. Fraessle:Technical University of Munich: Patents & Royalties. Busch:Juno Therapeutics/Celgene: Consultancy, Equity Ownership, Research Funding; Kite Pharma: Equity Ownership; Technical University of Munich: Patents & Royalties. Miyazaki:Nektar Therapeutics: Employment, Equity Ownership. Marcondes:Nektar Therapeutics: Employment, Equity Ownership. Riddell:Juno Therapeutics: Equity Ownership, Patents & Royalties, Research Funding; Adaptive Biotechnologies: Consultancy; Lyell Immunopharma: Equity Ownership, Patents & Royalties, Research Funding. Turtle:Allogene: Other: Ad hoc advisory board member; Novartis: Other: Ad hoc advisory board member; Humanigen: Other: Ad hoc advisory board member; Nektar Therapeutics: Other: Ad hoc advisory board member, Research Funding; Caribou Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; T-CURX: Membership on an entity's Board of Directors or advisory committees; Juno Therapeutics: Patents & Royalties: Co-inventor with staff from Juno Therapeutics; pending, Research Funding; Precision Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Eureka Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Other: Ad hoc advisory board member.

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Internet as a Source of Health Information and its Perceived Influence on Personal Empowerment

Health Information Systems ◽

10.4018/978-1-60566-988-5.ch060 ◽

2011 ◽

pp. 958-974

Author(s):

Guy Paré ◽

Jean-Nicolas Malek ◽

Claude Sicotte ◽

Marc Lemire

Keyword(s):

Health Information ◽

Internet Use ◽

Medical Information ◽

Sample Survey ◽

The Internet ◽

Health Issues ◽

Personal Empowerment ◽

Participative Approach ◽

Use Of The Internet ◽

Search For Information

The primary aim of this study is twofold. First, the authors seek to identify the factors that influence members of the general public to conduct Internet searches for health information. Their second intent is to explore the influence such Internet use has on three types of personal empowerment. In the summer of 2007 the authors conducted a household sample survey of a population of Canadian adults. A total of 261 self-administered questionnaires were returned to the researchers. Our findings indicate that use of the Internet as a source of health information is directly related to three main factors: sex, age and the individual’s perceived ability to understand, interpret and use the medical information available online. Further, their results lend support to the notion that using the Internet to search for information about health issues represents a more consumer based and participative approach to health care. This study is one of the first to relate Internet use to various forms of personal empowerment. This area appears to have great potential as a means by which consumers can become more empowered in managing personal health issues.

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Correlation Between Treatment Outcomes, Baseline Characteristics and Molecular Responses in the Majic Study Which Compared Ruxolitinib to Best Available Therapy in Essential Thrombocythemia

Blood ◽

10.1182/blood.v128.22.1929.1929 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1929-1929

Author(s):

Claire N. Harrison ◽

Adam Mead ◽

Sonia Fox ◽

Anesh Panchal ◽

Christina Yap ◽

...

Keyword(s):

Essential Thrombocythemia ◽

Research Funding ◽

Advisory Board ◽

Symptom Improvement ◽

Separate Analysis ◽

Molecular Response ◽

Molecular Responses ◽

Early Satiety ◽

Patient Reported ◽

Grade 3

Abstract MAJIC is a phase II trial of Ruxolitinib (RUX) vs Best Available Therapy (BAT) in essential thrombocythemia (ET) patients with resistance/intolerance to Hydroxycarbamide (HC) per European LeukemiaNet (ELN) criteria. Primary outcome was rate of complete hematological response (CHR) within 1 year (ELN criteria); secondary outcomes included partial HR, safety, thrombosis, hemorrhage, progression free survival (including transformation), molecular response (MR), symptom & quality of life (QOL) assessment. We present new data concerning molecular, symptom & clinical responses. Patients were stratified by JAK2V617F status, patient-reported symptoms & QOL determined using EQ5D, MDASI & MPN Symptom Assessment Form (MPN10), & compared using linear mixed models of post-baseline scores through month 12 adjusting for baseline; response was defined as ≥50% reduction in MPN10 total symptom score (TSS). JAK2/CALR/MPL allele burdens were assessed at baseline & 4 monthly. 110 patients were eligible for the modified ITT analysis, 58 (52%) & 52 (48%) in RUX & BAT arms respectively, comprising 44 males, 66 females, mean age 64.2ys, & resistant (24.5%), intolerant (51.8%) or both (22.7%) to HC. CHR was achieved in 27 (46.6%) of RUX patients vs 23 (44.2%) BAT patients (χ2 test p= 0.81). PHR occurred in 26 (44.8%) & 27 (51.9%) of RUX & BAT treated respectively. Grade 3 or 4 anemia occurred in 19% & 0% for RUX arm vs 0% (both grades) for BAT arm, grade 3 or 4 thrombocytopenia in 5.2% & 1.7% of RUX vs 0% (both grades) of BAT patients respectively. Grade 3 or 4 infections occurred in 10.3% of RUX patients vs 3.6% BAT arm. 9 RUX treated patients had 10 thrombotic events & 1 RUX patient a hemorrhage; vs 5 thrombotic & 5 hemorrhagic events in BAT patients (adjusted following central review). Transformations to post-ET MF occurred in 8 RUX vs 3 BAT treated patients, 1 RUX patient developed AML. 2 non-treatment related deaths occurred in each arm. Mean MPN-10 TSS & individual symptoms of early satiety & itching during the first 12 months were all significantly lower for RUX vs BAT (all p<0.05). Patients who achieved CHR had significantly better TSS, fatigue, inactivity, concentration problems, & MDASI symptom interference (all p<0.05) at baseline vs those without; however, scores during treatment did not appear to differ between CHR & non CHR groups after adjusting for these baseline differences. Allele burden during study & MRs (per ELN-IWG criteria Barosi Blood 2013) are shown in Table 1. Assays for JAK2 V617F were performed independently in 3 centres using qPCR (Guy's), TSCA NGS (Oxford) & amplicon-based NGS (Salisbury) & revealed Mean (range): JAK2 (Guy's): 33.2 (0.1-94.6), N=52; JAK2 (Oxford): 38.0 (0.5-92.2), N=52; JAK2 (Sal): 38.3 (0-90.0), N=50 (limited to JAK2 positive only). With Interclass Correlation Coefficient as follows ICC (Guy's v Oxford): 0.92 (95% CI 0.86-0.95) ICC (Guy's v Sal): 0.92 (95% CI 0.86-0.95) ICC (Oxford v Sal): 0.997 (95% CI 0.994-0.998). Notably MRs (n=5) only occurred with RUX treatment. There was no pattern of MR or progression with C/PHR or transformation, but 1 patient who transformed to PET MF had a complete MR. In a separate analysis baseline symptoms & QOL were not associated with JAK2, CALR, nor MPL status. Within RUX, baseline symptoms & QOL did not predict MR; however, fatigue, early satiety & abdominal discomfort (all p<0.05, Table 1) were significantly lower among those with MR vs not during treatment with a descriptively higher symptom response rate (2/4 [50%] vs 9/30 [30%]). Three non pre-specified multivariate analyses were performed to assess baseline factors influencing CHR (modelled for: treatment received, HC resistance or intolerance, white cell count, platelets, Hb & JAK2/CALR status); occurrence of ≥ grade 3 anemia or thrombocytopenia (modelled for: Hb (≥ 100g/dl) JAK2/CALR status); & transformation to PET-MF (modelled for: treatment, Hb ≤100g/dl). Only baseline Hb ≤100g/dl was significant for grade 3+ anemia (OR [95% CI]=0.17 [0.04, 0.72]), & PET-MF only occurred in patients with baseline WBC <10x109/L. This updated analysis shows that HC resistant/intolerant ET is clinically & molecularly diverse. We confirm that these patients are at high risk of thrombosis & transformation as suggested in prior retrospective studies. Molecular responses were limited to RUX & for the first time we demonstrate such responses may correlate with symptom improvement but not always with progression events. Disclosures Harrison: Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Incyte Corporation: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Mead:Novartis: Honoraria, Research Funding, Speakers Bureau. Aliman:Novartis: Other: Institutional funding and grant for international conference. . Chen:Novartis: Other: Advisory Board. Coppell:Novartis: Other: Travel, accommodation and conference attendance. Knapper:ONO pharmaceuticals: Research Funding; Novartis: Honoraria, Other: Travel and expenses for international conferences. Ali:Novartis: Honoraria, Other: Conference sponsorship, advisory board meetings. Hamblin:Novartis: Other: Advisory Board. Dueck:Bayer: Honoraria. Cross:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Mesa:Celgene: Research Funding; Promedior: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy. McMullin:Novartis: Honoraria, Speakers Bureau.

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Amphiregulin Improves Stratification of the Refined Minnesota Acute Graft-Versus-Host Disease Risk Score: Results from BMT CTN 0302/0802

Blood ◽

10.1182/blood.v130.suppl_1.72.72 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 72-72

Author(s):

Shernan G. Holtan ◽

Todd E. DeFor ◽

Joseph Pidala ◽

Nandita Khera ◽

Stephanie J. Lee ◽

...

Keyword(s):

Risk Score ◽

Research Funding ◽

Board Member ◽

Chronic Gvhd ◽

Threshold Level ◽

Advisory Board ◽

First Line ◽

Advisory Committees ◽

Graft Versus Host ◽

Hazard Ratios

Abstract Introduction: Amphiregulin (AREG) is an epidermal growth factor receptor (EGFR) ligand that can restore integrity to damaged intestinal mucosa in murine models of acute graft-versus-host disease (aGVHD). We previously described AREG as a circulating biomarker of late-onset aGVHD, but its relevance combined with clinical risk factors has not yet been tested in a large cohort of patients with aGVHD occurring prior to day 100 post-transplant. We therefore tested samples from two aGVHD first-line treatment trials, Blood and Marrow Transplant Clinical Trials Network (BMT CTN) 0302 and 0802, and identified a clinically relevant threshold level of circulating AREG at aGVHD onset. We then investigated whether incorporating AREG into the refined Minnesota Risk Score could further risk-stratify patients. Patients and Methods: Blood samples were obtained at the onset of systemic aGVHD treatment within BMT CTN 0302 (serum) and BMT CTN 0802 (plasma). All patients with response data and samples for analysis from both trials were included (N=251). We determined the association of AREG with clinical outcomes, including risk stratification by the refined Minnesota criteria, day 28 complete/partial response (CR/PR) to first-line therapy, 2-year overall survival (OS) and 6-month and 2-year non-relapse mortality (NRM). We investigated the effect of AREG on clinical endpoints per a doubling in the value of AREG, defined a clinically relevant threshold level in the AREG values using two-fold cross-validation, and confirmed the clinical relevance of this cut-point in independent samples (N=92) from pooled from drawn from the Chronic GVHD Consortium and the Mount Sinai Acute GVHD International Consortium (MAGIC). Results: In patients enrolled in BMT CTN 0302/0802, AREG levels were 1.7-fold higher in patients with Minnesota high-risk (HR) compared to standard-risk (SR) aGVHD (HR median 53.4 vs SR 31 pg/ml, p<0.01). Every 2-fold increase in AREG was associated with a 33% decrease in the likelihood of day 28 CR/PR (odds ratio [OR] 0.67, p<0.01, table). Clinical factors alone, as determined by the refined Minnesota Risk Score, were associated with day 28 CR/PR (p=0.02, table). Adding AREG to the Minnesota Risk Score could further risk-stratify patients. Minnesota SR patients with elevated AREG ≥ 33 pg/mL showed a 59% lower odds of day 28 CR/PR than SR patients with low AREG (OR 0.41, p=0.02). Patients with Minnesota HR aGVHD with AREG ≥ 33 pg/mL had the worst outcomes, with an 82% lower odds of day 28 CR/PR in comparison to HR with low AREG (OR 0.18, p<0.01). High AREG was associated with worse OS and NRM in both Minnesota SR (hazard ratios 2-year OS 2.3, p<0.01 and 6 month NRM 2.95, p=0.01, respectively) and HR patients (hazard ratios 2-year OS 3.35, p<0.01 and 6-month NRM 9.38, p<0.01 respectively, figure). Finally, in independent samples from the Chronic GVHD Consortium/MAGIC we confirmed that high AREG was associated with worse day 28 CR/PR (55.2% vs. 79.4%, p=0.02) and significantly worse 6-month survival after the onset of aGVHD (57.1% vs. 82.5%, p=0.01). Conclusion: AREG is elevated in patients with poor aGVHD outcomes and adds to the accuracy of risk stratification when combined with the refined Minnesota Risk Score. AREG ≥33 pg/mL at aGVHD onset is associated with lower day 28 CR/PR and higher mortality in samples from 4 multicenter cohorts. The mechanism of elevated circulating AREG in severe aGVHD is not yet known, although we hypothesize the degree of AREG elevation reflects the intensity of immune-mediated tissue injury resulting in AREG release. With accumulating evidence of altered EGFR ligands in aGVHD, further investigation into epithelial repair pathways involving AREG may lead to new adjunctive therapies to overcome poor steroid response in high-risk aGVHD. Disclosures Holtan: Incyte: Other: One-time advisory board member. Khera: Novartis: Consultancy. Lee: Mallinckrodt: Honoraria; Amgen: Other: One-time advisory board member; Bristol-Myers-Squibb: Other: One-time advisory board member; Kadmon: Other: One-time advisory board member. Chen: Immudex: Research Funding. Arora: Takeda Oncology: Consultancy. Flowers: Pharmacyclics: Consultancy. Cutler: Pfizer: Consultancy; Kite: Consultancy; Incyte: Consultancy; Bristol-Myers Squibb: Consultancy; Pharmacyclics: Consultancy; Astellas: Consultancy. Jagasia: Janssen: Consultancy, Research Funding; Therakos: Consultancy, Research Funding; Mallinckrodt: Consultancy. Hexner: Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Levine: Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. MacMillan: Magenta Therapeutics: Research Funding.

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Protective Role Immunoglobulin Replacement Therapy in Chronic Lymphocytic Leukemia: FOCUS on Subcutaneous Immunoglobulin Formulations

Blood ◽

10.1182/blood-2018-99-114867 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4954-4954

Author(s):

Andrea Visentin ◽

Francesca Romana Mauro ◽

Serena Rosati ◽

Silvia Imbergamo ◽

Edoardo Scomazzon ◽

...

Keyword(s):

Replacement Therapy ◽

Research Funding ◽

Board Member ◽

Advisory Board ◽

Antibody Deficiency ◽

Lymphocytic Leukemia ◽

Secondary Antibody ◽

Subcutaneous Immunoglobulin ◽

Grade 3

Abstract INTRODUCTION. Secondary antibody deficiency is a common complication in chronic lymphocytic leukemia (CLL) that could be present at diagnosis or can be acquired during the follow-up due to CLL progression, perturbation of non-neoplastic immune system and chemoimmunotherapy. Despite new and active target therapies a significant amount of CLL patients still develops severe and life-threatening infections. Intravenous immunoglobulin (IG) (IVIG) replacement therapy (IGRT) has been proven to be an effective supportive treatment in patients with primary and secondary antibody deficiency such as CLL. Subcutaneous immunoglobulin (SCIG) is a new valid treatment option that allows patients self-administration without access to the clinic which proved to be as effective as IVIG in primary immunodeficiencies. However, the activity SCIG is CLL patients with IG defect has been little investigated. The aim of this study was to retrospectively evaluate IG levels, infection rate and safety of patients treated with SCIG as compared to those managed with IVIG. METHODS. Inclusion criteria were: diagnosis of CLL according to iwCLL guideline, age >18 years, received at least 1 IVIG or SCIG infusion. IGRT was started according to hospital policies in patient with severe symptomatic hypogammaglobulinemia. The physician was responsible for the choice between IGRT formulations (the first patient received SCIG since Nov 2008). IG levels (IgG, IgA and IgM) were recorded within 3 months before starting IGRT (baseline), after 6 months and within three months from the last available follow-up. Continuous variables were compared with Wilcoxon's tests while categorical variables with Fisher's exact or Chi-square tests when appropriate. Time to IGRT discontinuation was calculated from the beginning IGRT to death or discontinuation (event) or last available follow-up /(censored). RESULTS. We gathered data from 116 CLL patients followed in 2 hematology centers who received IGRT: 63% were male, the median age at diagnosis was 58 years, 77 were at Binet A stage, 48% and 16% were unmutated IGHV and harbor TP53 abnormalities, respectively. 91% received at least one therapies, the median numbers of treatments were 3 (range 0-9) and 36% died during the follow-up due to infections in 22 cases, CLL progression in 5, Richter transformation in 6 patients and 9 other causes such as second cancers or major bleedings. Forty-nine patients received IVIG and 88 SCIG (41 the 20% formulation and 47 the 16% drugs). Despite similar basal and +6 months IgG levels, patients treated with SCIG achieved significant higher serum IgG at last available follow-up (3.99, 5.67 and 5.4 g/L vs 3.89, 6.07 and 6.22 g/L for IVIG and SCIG, p=0.0009). Both IgA and IgM levels remained stable during replacement therapy. While the number of grade 3-4 infections remain stable during IVIG (both 80% before and after IVIG), they decrease with SCIG (88% vs 64%, p<0.0019). Furthermore, the incidence of all and grade 3-4 infections decreased to 0.59 and 0.17, and 0.30 and 0.13 events/people/year with IVIG and SCIG, respectively. Incidences of infections was not higher in patients receiving oral inhibitors (i.e. ibrutinib, idelalisib and venetoclax). Adverse events during SCIG infusions occurred in 11% of subjects, most commonly skin reaction and pruritus. They were mild, limited to the site of infusion and easily to manage. Bruising did not increase during concomitant treatment of SCIG and ibrutinib. After a median duration of IGRT of 3.7 years (4.7 for IVIG and 3.1 for SCIG) 71% of subjects managed with IGEV discontinued therapy as compared to 36% of SC formulation (p<0.0001), 16% due to death in the former group as opposite to 9% of the latter. The estimated 3-year time to IGRT discontinuation were 44% vs 29% for IVIG and SCIG, respectively (p=0.2089). 29 patients shit from IVIG to SCIG, while none to opposite. We also observed that patients who shift from IVIG to SCIG were able to achieved higher IgG levels at last follow-up (median IgG 4.76 vs 6.62g/L, p<0.0001). CONCLUSIONS. In this study we described the clinical and biological characteristics of the bigger population with CLL and secondary hypogammaglobulinemia receiving IGRT. We demonstrated that SCIG are well tolerated, non-inferior to IVIG, they also allow to reach higher IgG through levels and to decrease the incidence of severe infections even during continuous CLL therapies. Disclosures Visentin: janssen: Consultancy, Honoraria. Mauro:abbvie: Other: board member; janssen: Other: board member. Foà:ROCHE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; INCYTE: Other: ADVISORY BOARD; NOVARTIS: Speakers Bureau. Trentin:Gilead: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Janssen: Research Funding.

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The Combination of Complex Karyotypes' Subtypes and IGHV Mutational Status Provides Prognostic and Predictive Information in Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood-2018-99-114721 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1844-1844

Author(s):

Andrea Visentin ◽

Laura Bonaldi ◽

Gian Matteo Rigolin ◽

Francesca Romana Mauro ◽

Annalisa Martines ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Research Funding ◽

Board Member ◽

Advisory Board ◽

Lymphocytic Leukemia ◽

Rank Test ◽

Predictive Information ◽

Excellent Outcome ◽

Mutational Status

Abstract INTRODUCTION. Complex karyotype (CK), defined by the presence of at least 3 chromosomal abnormalities, is a heterogeneous cytogenetic category associated with adverse prognosis in several hematologic malignancies. Recently, Rigolin et al. provided evidence that CK with major structural abnormalities (CK2) at chronic lymphocytic leukemia (CLL) diagnosis negatively impact on the time to first treatment (TTFT) and overall survival (OS) (Rigolin GM, BJH 2018). However, it is unknown whether the prognostic strength of CK could be implemented when combined with stable markers such as the IGHV mutational status. In the present study, we assessed the prognostic and predictive role of the combination of CK subtypes and IGHV status in a large CLL series. METHODS. Stimulated cytogenetics with CpG+IL2 was performed in 736 CLL patients in 3 referenced Italian hematological centers. According to Rigolin et al, CK2 cases included unbalanced translocations, addition, insertion, derivative and marker chromosomes. All other CK were classified as type 1 (CK1). An IGHV gene sequence homology >98% was considered as unmutated (U-IGHV), as opposed to mutated (M-IGHV). Treatment was initiated according to the iwCLL guidelines. TTFT and OS were calculated from diagnosis to first treatment or death, respectively, or last known follow-up. Survival curves were compared with the log-rank test and p<.05 was considered as significant. Harrell concordance index (c-index) was used to compare our prognostic model with Dohner's and FISH-IGHV models. RESULTS. We focused on 520 out of the 736 patients with cytogenetic and IGHV status assessed within 12 months from diagnosis. The median age at diagnosis was 63 years, 322 (62%) were males, 68% at Binet A stage, 45% U-IGHV, 48 harbored TP53 abnormalities, 99 a CK (28 CK1 and 71 CK2), 232 received at least one line of therapy (31% FCR, 16% BR, 8% ibrutinib, 5% chlorambucil-antiCD20, 40% other treatments) and 80 died over a median follow-up of 5.8 years. 71 (14%) harbored CK2, 214 (41%) CK1 or U-IGHV and 235 (45%) M-IGHV without CK2. The former group were characterized by a higher prevalence TP53 (38% vs 8% vs 3%, p<0.0001) and cytogenetics abnormalities but lower cases with low-risk FISH (i.e. 13q or normal; 38% vs 54% vs 91%, p<0.0001) as compared with others two groups. We observed that subjects with CK2 had a shorter TTFT (median years 1.97, 3.40 and 19.1, p<0.0001) and 5 years OS (67%, 85%, 93%, p<0.0001) compared to cases with CK1/U-IGHV, or M-IGHV without CK. These data were confirmed in multivariate analysis. The worse prognosis of CK2 patients was independent of TP53 status (p values 0.0770 and 0.8122 for TTFT and OS, respectively). The c-indexes for our model were 69% and 68% for TTFT and OS, respectively, and were not inferior to those calculated with Dohner's (64% and 61%) and FISH-IGHV (69% and 63%) models. The combination of these two markers also provides predictive information after first-line therapy (p<0.0001 for both TTFT and OS). In particular, among 107 patients treated with FCR or BR just one of the M-IGHV cases relapsed but none died after a median follow-up of 43 months as compared with the other two subgroups (3-year PFS 92%, 69% and 23%, p<0.0001; 3-year OS: 100%, 94%, 62%, p<0.0001). CONCLUSIONS. In this study, we demonstrated that the combination of CK subtypes and IGHV status provides important prognostic and predictive data in CLL. Moreover, our model was not inferior to other commonly used prognostic scores. While patients with M-IGHV without any subtypes of CK showed an excellent outcome with chemoimmunotherapy, new alternative therapies should be explored for patients with CK2. Disclosures Visentin: janssen: Consultancy, Honoraria. Rigolin:Gilead: Research Funding. Mauro:abbvie: Other: board member; janssen: Other: board member. Foà:JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; NOVARTIS: Speakers Bureau; INCYTE: Other: ADVISORY BOARD; CELTRION: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau. Cuneo:Roche: Other: advisory board, Speakers Bureau; Gilead: Other: advisory board, Speakers Bureau; Abbvie: Other: advisory board, Speakers Bureau; janssen: Other: advisory board, Speakers Bureau. Trentin:Gilead: Research Funding; Janssen: Research Funding; Abbvie: Honoraria; Roche: Membership on an entity's Board of Directors or advisory committees.

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Education and Consumer Informatics

Yearbook of Medical Informatics ◽

10.1055/s-0038-1638693 ◽

2010 ◽

Vol 19 (01) ◽

pp. 72-74 ◽

Cited By ~ 1

Author(s):

C. Boyer ◽

Keyword(s):

Health Information ◽

Health Informatics ◽

Medical Information ◽

Age Groups ◽

The Internet ◽

Consumer Health ◽

The Public ◽

Nhs Direct ◽

Consumer Informatics ◽

Number Of Individuals

Summary Objectives: To evaluate the extent to which the Internet is accessed for health information and perceived as useful to varying groups classified primarily according to age. Method: Synopsis of the articles on education and consumer health informatics selected for the IMIA Yearbook of Medical Informatics 2010. Results: A growing number of individuals are actively seeking health information through a varying selection of resources. The Internet is now seen as a major source of health information alongside with books and other means of paper-based literature. However, it is not clear how the Internet is perceived by varied groups such as those coming from differing age groups. Conclusion: The papers selected attempt to obtain a better understanding about how the public perceives and uses the Internet as an information gathering tool—especially for health information. The papers also explore into how the Internet is used by different groups of people. As all online health information is not of uniform quality, it is important to access and rely on quality medical information. This issue is also dealt with, where the popularity of Wikipedia is measured with the popularity of reliable web sources such as Medline Plus and NHS Direct.

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Internet as a Source of Health Information and its Perceived Influence on Personal Empowerment

International Journal of Healthcare Information Systems and Informatics ◽

10.4018/jhisi.2009071001 ◽

2009 ◽

Vol 4 (4) ◽

pp. 1-18 ◽

Cited By ~ 3

Author(s):

Guy Paré ◽

Jean-Nicolas Malek ◽

Claude Sicotte ◽

Marc Lemire

Keyword(s):

Health Information ◽

Internet Use ◽

Medical Information ◽

Sample Survey ◽

The Internet ◽

Health Issues ◽

Personal Empowerment ◽

Participative Approach ◽

Use Of The Internet ◽

Search For Information

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E-Health Dot-Coms' Critical Success Factors

Electronic Commerce ◽

10.4018/978-1-59904-943-4.ch163 ◽

2011 ◽

pp. 2134-2142

Author(s):

Abrams A. O’Byuonge ◽

Leida Chen

Keyword(s):

Health Care ◽

Health Information ◽

Health Care System ◽

Web Site ◽

Medical Information ◽

The Internet ◽

Health Care Information ◽

Care Information ◽

The Web ◽

Care System

The increasing use of the Internet by consumers gave rise to an information boom to health-care consumers. Not only could the Internet be used as a communication tool to provide information that would allow patients to make informed decisions, but it could also be used to generate revenue for investors. The dot-com boom of the late 1990s exploited this opportunity, targeting the health-care system, a $1.7 trillion market in the United States alone. Overall, the health-care system is wasteful and costly (Itagaki, Berlin, & Schatz, 2002), and as a result, health-care IT was touted as the magic pill for cutting costs. The Internet boom of the late 1990s saw the emergence of e-health: the delivery of health services and health information through the Internet and Internet-related technologies (Eysenbach, 2001). Leading the many entrepreneurs and venture capitalists who stepped in to seize a piece of the health-care industry cake were WebMD Corp., an online provider of medical information for doctors and consumers in Elmwood Park, New Jersey, and DrKoop.com, an Austin, Texas-born company that later moved to Santa Monica, California, and began doing business as Dr. Koop LifeCare Corp. Dr. C. Everett Koop, the former U.S. surgeon general, had spent over 6 decades in the medical profession. He envisioned the Internet as an opportunity to change the health-care delivery system in order to empower individuals to take charge of their own health care (Musselwhite, 2002). With this vision and his reputation as an advocate for health-care reform, along with the help of two budding entrepreneurs, Don Hackett and John Zacarro, the trio opened a business-to-consumer Internet portal: DrKoop.com. The portal was designed to provide health information to consumers in areas such as chronic illness, food and nutrition, fitness, and medical breakthroughs. At the beginning, the Web site was an overwhelming success, receiving a million hits per month after 2 years of operation, and about 4 million unique visitors per month at its peak. The portal included a personal medical-records system that facilitated the cross-referencing of medications for interactions, as well as the storage of medical reports that could then be accessed by both patients and physicians. DrKoop.com’s public woes began in February 2000 when its auditor, PricewaterhouseCoopers, issued a “going concern qualification,” an ominous warning that highlighted the precarious financial situation the Internet-based health service was in Cleary (2000). By the end of 2000, DrKoop.com was still struggling, and in the first 9 months of 2001 alone, the company’s losses were nearly 3 times its revenue. According to the Securities and Exchange Commision (SEC) filings, from January 1999 until the service’s liquidation in September 2001, DrKoop.com’s losses stood at $193.6 million, dwarfing the $41 million revenue generated during the period. At the site’s peak in July 1999, DrKoop.com’s stock rose to $45.75 per share on the NASDAQ, but was worth $0.12 at the time of bankruptcy filing. In July 2002, Vitacost.com, a privately held online seller of nutritional supplements, paid a paltry $186,000 in cash for DrKoop.com’s assets, which included the brand name, trademarks, domain names, the Web site, and the e-mail addresses of its registered users. WebMD, originally called Healtheon/WebMD, was founded by Jim Clark, who also founded Silicon Graphics and Netscape. Clark’s vision was to connect insurance companies, doctors, and patients over the Internet in order to lower costs and reduce paper trails. Rather than building its own products and services, Healtheon used its highly valued stock to finance acquisitions of leading companies in the industries it targeted. In 1999, it acquired WebMD.com and OnHealth, both leading health portals, giving it access to the consumer health market (Salkever, 2000). Though WebMD lost $6.5 billion on revenue of $530.2 million in the first 9 months of 2001, it still continued to expand long after DrKoop.com had dropped off the radar screen. For the fiscal year ending in December 2003, WebMD reported revenues of $964 million, an increase of 10.6% on the previous year’s revenues, which totaled $871.7 million. Of the 11 health-care mergers and acquisition deals in the first 7 months of 2004, valued at $900 million, WebMD was the leading acquirer (Abrams, 2004). Two of WebMD’s high-profile acquisitions in 2004 were the $160 million cash purchase of ViPS, a privately held provider in Baltimore, Maryland, of information technology to the government, Blue Cross-Blue Shield, and other health-care insurers; and the $40 million acquisition of Dakota Imaging Inc., a private company in Columbia, Maryland, that offered automated health-care claims processing technology. As industry leaders, WebMD and DrKoop.com faced competition from both health-care information portals (such as HealthGrades.com, MDConsult, ZoeMed.com) and online pharmacies that provided consumers with one-stop shopping for medications and medical information (Walgreens.com, drugstore.com, Webvan.com). The threat from the health-care information portals, nevertheless, was minimal due to their limited brand recognition and information coverage. In the online pharmacy sector, however, Walgreens.com gained a substantial market share by combining the best of both worlds: complementing its physical stores located throughout the country by offering online customer service, convenience, and real-time access to a health library that provided comprehensive information on prescription drugs, insurance, and health issues.

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