Increased clinic awareness and attitudes of independence through client advisory board membership

James K. Morrison; Harold Yablonovitz

doi:10.1007/bf00885527

Sickle Stroke Screen: A Patient-Centered Educational Initiative for Children with Sickle Cell Anemia in the Displace Consortium

Blood ◽

10.1182/blood-2020-141963 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 43-44

Author(s):

Alyssa M Schlenz ◽

Shannon Phillips ◽

Martina Mueller ◽

Cathy L Melvin ◽

Robert J Adams ◽

...

Keyword(s):

Needs Assessment ◽

Board Of Directors ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Stroke Prevention ◽

Stroke Risk ◽

Advisory Board ◽

Educational Initiative ◽

Advisory Committees ◽

Board Membership

Introduction: The NHLBI funded Dissemination and Implementation of Stroke Prevention Looking at the Care Environment (DISPLACE) study was designed to improve implementation of stroke prevention guidelines in children with sickle cell anemia (SCA), particularly implementation of transcranial Doppler (TCD) ultrasound for identifying individuals at risk of stroke. The study consists of 3 phases: 1) evaluating current stroke risk screening practices, 2) exploring barriers and facilitators to guideline implementation (needs assessment), and 3) designing and implementing interventions to improve stroke risk screening. A key barrier identified through qualitative methods during the needs assessment was a gap in education, including an overall lack of understanding among patients and caregivers of the purpose of TCD screening. This abstract describes the process of developing one of the interventions for phase 3, a rebranding and educational initiative. Methods: During the needs assessment, 27 key informant interviews and 173 complete surveys were conducted with individuals with SCA and their caregivers. Transcripts from the interviews and survey responses were reviewed to better understand the extent of educational gaps described by families as well as to guide initial rebranding prototypes. Prototypes were developed by the study team, including a new name and logo for TCD as well as an infographic. An interview guide was then created to obtain feedback on the prototypes from individuals with SCA and/or the parent or primary caregiver from two sites in the consortium. Cue cards with prototypes were included with prompts for the "think aloud" method to be applied during interviews. Cue cards were presented first with prototypes for the new name in black font on a white background to solicit feedback on the wording alone. Then, cue cards included various layouts, fonts, and graphics with the prototype names for in-depth feedback on the logo appearance. Finally, participants were asked questions pertaining to the infographic. Results: Twenty interviews were conducted with individuals with SCA and/or the parent/caregiver at two DISPLACE sites. Almost all participants (95%) made the connection between the wording prototypes and TCD without prompting. Many participants expressed that the word "stroke" in both options was "scary," and sometimes chose the option that was "less scary to them." However, many participants also felt that the word "stroke" was necessary to explain the reason for the procedure and would prompt families to ask about the screening as opposed to making them more fearful. The majority of participants (60%) chose "Sickle Stroke Screen" over "Stroke Risk Screen." Participants reported preferring this wording because it is specific to SCA, was easier to remember and represented a less "scary" option. The most commonly preferred logo is presented in Figure 1. Participant reasons for selecting this option were: it is easier to read; they preferred the stacked layout; it is less spread out; they liked the bold letters; it is more eye catching; and it includes the words "sickle cell" in the logo. When asked about preferences for an infographic, the majority described including a picture of a brain. Nearly all participants believed a reassuring message was needed to balance out the fear of the word "stroke." The message, "knowledge is power" provided this balance and resonated with nearly all participants (95%). Figure 2 presents the infographic developed based on participant feedback. Conclusions: Results from this educational rebranding effort highlight the importance of understanding patient and family educational gaps and incorporating their perspective and feedback into educational campaigns. The new logo and infographic were integrated into an educational pamphlet, informative posters and other material designed by the DISPLACE site principal investigators. Part 3 of the study is underway including implementation of the educational initiative at the DISPLACE sites. The new terminology and logo have also been broadly distributed throughout the US through community-based organizations to other patients, families, and stakeholders. Disclosures Kanter: AGIOS: Membership on an entity's Board of Directors or advisory committees; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; Wells Fargo: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; BEAM: Membership on an entity's Board of Directors or advisory committees.

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Ruxolitinib and Lenalidomide As a Combination Therapy for Patients with Myelofibrosis

Blood ◽

10.1182/blood.v124.21.1831.1831 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1831-1831 ◽

Cited By ~ 2

Author(s):

Daver Naval ◽

Jorge E. Cortes ◽

Elias Jabbour ◽

Naveen Pemmaraju ◽

Nitin Jain ◽

...

Keyword(s):

Median Time ◽

Research Funding ◽

Dose Adjustment ◽

Financial Constraints ◽

Single Agent ◽

Advisory Board ◽

Dose Increase ◽

Median Response ◽

Board Membership ◽

Grade 3

Abstract Background: Ruxolitinib (RUX) is a potent and selective inhibitor of the JAK/STAT pathway that significantly abrogates splenomegaly and constitutional symptoms in patients (pts) with myelofibrosis (MF). Lenalidomide (LEN) is a second-generation immunomodulatory agent that may improve MF-associated anemia and thrombocytopenia. RUX and LEN possess complimentary efficacy profiles. Aim:Our single-center phase II open-labeled study was conducted to determine the efficacy and safety of the combination of RUX with LEN in pts with MF. Objective improvements were defined using International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) 2007 criteria. We were cognizant of an overlapping toxicity of the two medications, namely myelosuppression. Methods:Pts received 15 mg RUX orally twice daily in continuous 28-day cycles with 5 mg LEN orally once daily on days 1-21. Dosage was reduced, increased or delayed based on the assessment of efficacy and toxicity. Results: Thirty-one pts were enrolled between October 2011 and August 2013. Twenty-one (68%) had received prior treatment, including 2 with thalidomide. After a med follow-up of 21.6 mo (1.9-27.7), 28 pts remain alive. The median time on study was 14.7 mo (1.8-26.6) and the median number of cycles administered was 15 (1-29). Simultaneous administration of RUX and LEN was difficult. Only 2 (6%) pts have not required a dose interruption/dose adjustment. The median time to first dose interruption/dose adjustment was 56 days (4-360). Among the 29 pts who needed a dose interruption/adjustment, 23 (79%) needed it within 3 months of starting therapy. The first change in 23 (74%) pts was a dose interruption: median time to first dose interruption was 56 days (4-360), with 20 (87%) of the dose interruptions occurring within 3 months of therapy. LEN was held in all 23 pts and 14 (61%) never restarted LEN. RUX was concurrently held in 7 (30%), reduced in 9 (40%), and continued at same dose in 7 (30%). Reasons for the first dose interruption were low platelets (n=8), low absolute neutrophil count (n=3), anemia (n=3), diarrhea (n=3), financial constraints (n=2), deep vein thrombosis (n=1), skin rash (n=1), transaminitis (n=1), and arthralgia/fever (n=1). The first change in 6 (19%) pts was a dose increase (all in RUX): median time to dose increase was 83 days, with 3 (50%) of the increases occurring within 3 months of starting therapy. The reasons for dose increase were leukocytosis (n=2), suboptimal response (n=2), increased spleen size (n=1), and thrombocytosis (n=1). At the time of submission, 18 pts remain on study: 7 on RUX alone and 11 on both medications. IWG-MRT defined clinical improvement (CI) in splenomegaly was noted in 11 (36%) pts. Of note, CI in splenomegaly was seen in 6 of 11 (55%) pts who did not require a dose interruption in the first 3 months. Median time to response was 1.0 mo (0.4-9.1) and median response duration was 19.3 mo (9.4-25.6+). An additional 18 (58%) pts had IWG-MRT defined stable disease. Reasons for discontinuation in 13 pts were lack of response (n=2), infection (n=2), progression (n=1), neuropathy (n=1), renal failure (n=1), diarrhea (n=1), myelosuppression (n=2), concurrent lymphoma (n=1), and financial constraints (n=2). Grade 3/4 myelosuppression was noted in 13 pts. Five pts experienced grade 3/4 non-hematological toxicity (related and unrelated): G3 diarrhea (n=1), G3 edema (n=1), G4 acute kidney injury (n=1), and G3 liver enzyme (n=2). Conclusion: Concomitant administration of RUX with LEN resulted in early dose interruption in a majority of pts. Most pts were unable to restart LEN after dose interruption. Starting the two drugs simultaneously compromised the expected efficacy of RUX alone. A sequential approach with single-agent RUX for the first 3-6 months followed by the addition of the second agent once a steady dose of RUX has been achieved and optimal benefit reached may be a more viable approach for future RUX combination strategies. Table 1: Pt characteristics (N = 31) Characteristic N (%) / [range] Median age, years 66 [37-82] Male 18 (58%) Diagnosis Post-essential thrombocytosis MF Post-polycythemia MF Primary MF 4 (13%) 12 (39%) 15 (48%) Splenomegaly 28 (90%) Median WBC x 109/L 19.0 [4.3-124.9] Median hemoglobin g/dL 11.0 [8.9-17.5] Median platelets x 109/L 250 [27-1898] Peripheral blood blasts ³ 1% 15.0 (48%) JAK2 + 26 (84%) Cytogenetics Diploid 18 (58%) Abnormal 12 (39%) Insufficient metaphases 1 (3%) Disclosures Naval: Incyte: Advisory board membership Other, Research Funding. Pemmaraju:Incyte: Advisory board membership Other. Verstovsek:Incyte: Research Funding.

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High Surface IgM Levels Associate with Shorter Response Duration and Bypass of the BTK Blockade during Ibrutinib Therapy in CLL Patients

Blood ◽

10.1182/blood-2019-128899 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1752-1752 ◽

Cited By ~ 1

Author(s):

Giorgia Chiodin ◽

David Dutton ◽

Enrica Antonia Martino ◽

Samantha Drennan ◽

Ian Tracy ◽

...

Keyword(s):

Research Funding ◽

High Surface ◽

Single Agent ◽

Advisory Board ◽

Lymphocytic Leukemia ◽

Educational Support ◽

Time Points ◽

Board Membership ◽

Duration Of Response ◽

The University

The circulating tumor cells of chronic lymphocytic leukemia (CLL) are characterized by variably low surface IgM (sIgM) levels and signaling capacity, consequent to stimulation by tissue-based antigen. The variability is evident in both CLL subsets with unmutated and mutated immunoglobulin genes and affects tumor cell survival and proliferation. This appears clinically important because CLL with relatively higher sIgM levels/signaling capacity progress more rapidly than those with lower sIgM levels/signaling capacity (D'Avola, Blood 2016), likely due to a larger proliferative component at tissue sites. B-cell receptor (BCR)-signaling inhibitor ibrutinib exerts its therapeutic activity in CLL by irreversibly binding the Bruton's tyrosine kinase (BTK) at Cys481 in the active site. This leads to redistribution of CLL cells from tissue sites into peripheral blood and to a selective recovery of sIgM levels and function, consequent to release from antigen drive at tissue sites (Drennan, Clin Cancer Res 2019). We have now investigated the hypothesis that sIgM levels on the CLL cells affect duration of response to ibrutinib therapy possibly consequent to circumvention of the pharmacological BTK inhibition. Seventy CLL patients participating in the "real-world" observational study at the University of Southampton (NIHR/UKCRN ID: 31076) were investigated for phenotypic, molecular and functional characteristics associated with response to single-agent ibrutinib. Time to progression requiring a new treatment from ibrutinib start (TTNT) was used as primary endpoint to measure duration of response. The levels of sIgM were measured by flow cytometry. Anti-IgM induced signaling was determined by immunoblotting or iCa2+ mobilization. BTK and PLCγ2 mutations were determined using the Illumina NexteraXT kit and a MiSeq at the University of Southampton and validated independently at Karolinska Institutet. Our previous cut-offs of 50 (MFI) or 5 (iCa2+ % mobilization) were used to distinguish patients with high/low sIgM levels or signaling capacity, respectively. Median follow-up from ibrutinib start was 42 months (range 12-70). Pre-ibrutinib sIgM levels (range 7-618, median 65; high sIgM MFI 46/70, 66%) and sIgM signaling capacity (range 1-98; median 45; high sIgM signalers 56/70, 80%) were broadly heterogeneous. However, median values were significantly higher than the general CLL population at diagnosis, as expected in progressive CLL. By univariate analyses of clinical, phenotypic, FISH and immunogenetic characteristics for TTNT, high sIgM was the only parameter predicting shorter duration of response to ibrutinib (p=0.02). Only 2/24 CLL with low sIgM levels (CLLIgM_lo) had progressed (median TTNT not reached) compared to 15/46 CLL with high sIgM (CLLIgM_hi, 14% at 12 months, 18% at 24 months, 34% at 36 months, 44% at 42 months) during therapy. The levels of sIgM correlated significantly with sIgM signaling capacity prior to treatment (r= 0.68; p<0.0001) and were selectively maintained during ibrutinib therapy. From in vitro analysis of 13 therapy-naive CLL samples, the degree of inhibition by ibrutinib of anti-IgM induced signals downstream to BTK correlated negatively with sIgM levels (r=-0.68,p=0.01) and signaling (r=-0.71,p=0.009). Anti-IgM induced signals were then measured in 12 patients (7 CLLIgM_hi, 5 CLLIgM_lo) after 1, 4 and 12 weeks of ibrutinib therapy. These patients had not acquired BTK or PLCγ2 mutations and BTK phosphorylation appeared completely inhibited at all time-points. Mean anti-IgM induced iCa2+ mobilization and ERK1/2 phosphorylation were significantly reduced but not abolished during therapy and degree of inhibition was variable between individuals. Remarkably, degree of inhibition of anti-IgM-induced iCa2+ mobilization and pERK1/2 was significantly lower in CLLIgM_hi than in CLLIgM_lo (p<0.05 at all time-points). These results confirm that sIgM signaling is dependent on sIgM levels and that it can circumvent BTK blockade when sIgM levels are high. They suggest that high sIgM signaling can drive ibrutinib resistance despite ability of ibrutinib to fully occupy the BTK phosphorylation pocket. A possibility is that those CLL cells with high sIgM represent a potentially dangerous subpopulation equipped to migrate to tissue and to receive proliferative stimuli. These cells might be targeted by a combinatorial therapeutic approach with ibrutinib. Disclosures Johnson: Takeda: Honoraria; Kite: Honoraria; Bristol-Myers Squibb: Honoraria; Genmab: Honoraria; Incyte: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Epizyme: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria. Duncombe:Abbvie: Other: Advisory Board membership;Educational support; Gilead: Other: Advisory Board membership; Janssen: Other: Advisory Board membership;Educational support; Novartis: Other: Advisory Board membership. Scarfo:Janssen: Honoraria; AstraZeneca: Honoraria; AbbVie: Honoraria. Sutton:Gilead: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Ghia:Pharmacyclics LLC, an AbbVie Company: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; ArQule: Consultancy, Honoraria; Dynamo: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Juno/Celgene: Consultancy, Honoraria; BeiGene: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria; Novartis: Research Funding; Sunesis: Consultancy, Honoraria, Research Funding. Forconi:Roche: Honoraria; Janssen-Cilag: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Menarini: Consultancy; Novartis: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; Gilead Sciences: Research Funding.

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Phase I/II Study of Vosaroxin and Decitabine in Newly Diagnosed Older Patients (pts) with Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)

Blood ◽

10.1182/blood.v124.21.385.385 ◽

2014 ◽

Vol 124 (21) ◽

pp. 385-385 ◽

Cited By ~ 4

Author(s):

Daver Naval ◽

Hagop M. Kantarjian ◽

Guillermo Garcia-Manero ◽

Naveen Pemmaraju ◽

Tapan M. Kadia ◽

...

Keyword(s):

Bone Marrow ◽

High Risk ◽

Phase I ◽

Research Funding ◽

Overall Response Rate ◽

Response Rate ◽

Advisory Board ◽

Standard Chemotherapy ◽

Overall Response ◽

Board Membership

Background: Vosaroxin, is a first-in-class anti-cancer quinolone derived (AQD) DNA topoisomerase II inhibitor, which is not a substrate for p53 or P-glycoprotein, has limited toxicity, and is currently under evaluation for the treatment of pts with AML and high-risk MDS. Methods: Pts were eligible if they had AML or high-risk MDS (defined as having ³ 10% blasts in the bone marrow), were 60 years of age or older, and had adequate performance status (ECOG ² 2) and organ function. Pts younger than 60 who were unsuitable for standard chemotherapy were also eligible. In the phase I part of the study the first six pts received vosaroxin 90 mg/m2 daily on days 1 and 4 with decitabine 20 mg/m2 daily for 5 days. This dose was well tolerated with no dose limiting toxicity identified and pts were then enrolled on phase II at this dose and schedule. However, due to mucositis in a few subsequent pts, the induction dose of vosaroxin was reduced to 70 mg /m2, starting with pt #25. The vosaroxin dose could be maintained at 70 mg/m2 or reduced to 50 mg/m2 in consolidation cycles, which were repeated in approximately 4 to 5-week intervals for a total of up to 7 cycles. Dose adjustments and dose delays of one or both agents, were allowed based on toxicity. The primary endpoint was to determine the overall response rate including complete response (CR) + CR without platelet recovery (CRp) + CR with insufficient hematological recovery (CRi). Secondary endpoints were: CR duration, disease-free survival, overall survival, safety, and early mortality. Results: To date, 35 pts (32 AML, 3 high-risk MDS) with a median age of 71 years (range, 41-78) have been enrolled; 34 (97%) pts were older than 60 years. They included 15 (43%) pts with diploid cytogenetics, 12 (34%) with complex cytogenetic abnormalities including chromosome 5 and/or 7 abnormalities, and 8 (23%) with other miscellaneous abnormalities. 13 (37%) pts with AML had antecedent hematological disorders (AHD) including 7 (20%) with MDS, 4 (11%) with myeloproliferative neoplasm and 2 (6%) with MDS/MPN. Three pts with AHD had received prior therapy including 5-azacytidine (n=1), ruxolitinib + 5-azacytidine (n=1), and lenalidomide (n=1). Additionally, 5 (15%) pts had therapy-related disease with prior exposure to chemotherapy or radiation therapy. Median bone marrow blast %, median white blood cell, hemoglobin, & platelet counts were 40% (9-97), 4.1 x 109/L (0.4-57.0), 9.4 g/dL (6.8-11.5), and 40 x 109/L (7-333), respectively. 34 pts were evaluable for response; 17 (50%) achieved CR, 6 (18%) CRp, and 3 (9%) CRi for an overall response rate of 77%. One pt is too early for response assessment. Responses by age, cytogenetic and molecular characteristics are shown in table 1. The median follow-up is 5.1 months (range, 0.9-11.0). Pts have received a median of 2 (1-6) treatment cycles with the median number of cycles to response being 1 (1-4). Three pts have relapsed and the median duration of CR/CRp/CRi has not been reached (0.5-9.9+ months). Four (12%) pts have proceeded to allogeneic stem cell transplant (ASCT). 4-week and 8-week mortality were 0% and 14%, respectively. The regimen is well tolerated with the main grade ³ 3 toxicity being mucositis in 9 (26%) pts and liver enzyme elevation in 3 (9%). Conclusion: Combination of vosaroxin and decitabine is effective and feasible in older pts with AML and high-risk MDS. Enrollment is ongoing. Table 1: Response by baseline characteristics Parameter Category N Overall response Too early to evaluate Age* 60-70 16 14/16 (88%) 0 >70 18 12/17 (71%) 1 Cytogenetics Diploid 15 11/14 (79%) 1 -5/-7/other adverse 12 8/12 (67%) 0 Miscellaneous 8 5/8 (63%) 0 Mutation Status IDH2 7 7/7 (100%) 0 IDH1 5 1/4 (25%) 1 TP53 9 6/9 (67%) 0 RAS 9 4/9 (44%) 0 *1 pt below the age of 60 years was unsuitable for standard chemotherapy and was enrolled on study. Disclosures Naval: Sunesis: Advisory board membership Other, Research Funding. Off Label Use: Vosaroxin (Qinprezo) has not been approved for AML. In this clinical trial we are evaluating the efficacy and safety of vosaroxin (Qinprezo) in combination with decitabine in elderly patients with AML. . Kantarjian:ARIAD, Pfizer, Amgen: Research Funding. Kadia:GSK: Research Funding; ARIAD: Honoraria. Borthakur:Tetralogic Pharmaceuticals: Research Funding. Jabbour:Ariad, Novartis, BMS, Pfizer, and Teva: Consultancy. Cortes:Ariad: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Consultancy, Research Funding. Craig:Sunesis: Employment. Ravandi:Sunesis: Advisory board membership Other, Research Funding.

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REVIEWERS FOR VOLUME 73

Edinburgh Journal of Botany ◽

10.1017/s0960428616000184 ◽

2016 ◽

Vol 73 (3) ◽

pp. 375-375

Keyword(s):

Advisory Board ◽

Editorial Advisory

Many papers submitted to the Edinburgh Journal of Botany are reviewed by members of the Editorial Board and Editorial Advisory Board. The members of both Boards wish to express their thanks to the following, who have also kindly reviewed papers during the preparation of this volume.

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