Cheville, Andrea

5554 Background: A better understanding regarding the burden of treatment side effects in patients with gynecological malignancies could help guide symptom interventions and oncologic therapy decision-making. We aim to inform understanding of symptom burden in epithelial ovarian cancer (EOC) by analyzing patient-reported symptom data from patients treated for this condition over a 16-month period. Methods: Patients receiving medical oncology care at Mayo Clinic Rochester and at Midwest Mayo Clinic Health System community sites have received symptom-focused surveys prior to each medical oncology visit since March 28, 2019 through the Enhanced Electronic Health Record Facilitated Cancer Symptom Control Study (E2C2). These surveys, administered either through the electronic medical record portal or on a clinic tablet prior to each oncology office visit, no more frequently than every 2 weeks, include six linear analogue scales measuring sleep disturbance, pain, anxiety, emotional distress, and fatigue (SPADE), as well as physical dysfunction on a scale of 0 (none) to 10 (as bad as you can imagine). Scores of 0-3 were considered mild symptoms, 4-6 moderate symptoms, and 7-10 severe symptoms. We collected survey results from March 28, 2019 to July 20, 2020 for patients with EOC and reviewed the number of surveys per patient in addition to the average symptom scores. Results: From March 2019 to July 2020, for patients with EOC, there were 2974 encounter-based surveys from 762 patients. The number of surveys completed by each patient ranged from 1-20. The following number of patients returned the correlating number of surveys: 1 survey:240 patients; 2 surveys:145; 3 surveys:79; 4 surveys:56; 5 surveys:58; 6 surveys:45; 7 surveys:38; 8 surveys:27; 9 surveys:22; ≥10 surveys:52. The average score from all surveys for each symptom was: 2.41 for sleep disturbance, 2.03 for pain, 2.32 for anxiety, 1.97 for emotional distress, 3.26 for fatigue, and 2.50 for physical dysfunction. Please see the table for the proportion of surveys that reported symptoms as mild, moderate, or severe. Conclusions: Fatigue and physical dysfunction were reported most frequently in patients with EOC, while emotional distress and pain were reported least frequently. 20% of surveys reported moderate to severe emotional distress, while 40% reported moderate to severe fatigue. A targeted approach to symptom management is needed for patients undergoing EOC evaluation and treatment. Our next steps in this analysis include an assessment of potential predictors of greater symptom burden (e.g., specific treatments, age, and other clinical and sociodemographic characteristics). Clinical trial information: NCT03892967. [Table: see text]

BACKGROUND: There is a continued perception that intravenous line (IV) placement is contraindicated in the arm ipsilateral to prior breast cancer surgery to avoid breast cancer–related lymphedema (BCRL). The aim of this retrospective study was to determine the risk for development of BCRL in ipsilateral arm IV placement compared to contralateral arm IV placement to prior breast cancer surgery. METHODS: We performed a retrospective review, via our Integrated Clinical Systems and Epic Electronic Heath Record of IV placement for anesthesia and surgery in patients with a prior history of breast cancer surgery with or without axillary lymph node dissection. Complication rates were compared for IVs placed in the ipsilateral and contralateral arms. We identified 3724 patients undergoing 7896 IV placements between January 1, 2015, and May 5, 2018, with a prior history of breast cancer surgery via their index anesthesia and surgical procedures. RESULTS: The median time from breast cancer surgery to IV placement was 1.5 years (range, 1 day to 17.8 years). Of 2743 IVs placed in the arm contralateral to prior breast cancer surgery, 2 had a complication, corresponding to an incidence of 7.3 per 10,000 (95% confidence interval [CI], 0.9–26.3 per 10,000). Of 5153 IVs placed in the arm ipsilateral to prior breast cancer surgery, 2 IVs had a complication, for an incidence of 3.9 per 10,000 (95% CI, 0.5–14.0 per 10,000). The frequency of complications was not found to differ significantly between the groups ( P = .91), and the 95% CI for the risk difference (ipsilateral minus contralateral) was −23 to +8 complications per 10,000. The complication rate is similar when only the first IV placed following breast cancer surgery is considered (overall 5.4 per 10,000 [95% CI, 0.7–19.4] per 10,000; contralateral 7.0 [95% CI, 0.2–39.0] per 10,000, ipsilateral 4.4 [95% CI, 0.1–24.2] per 10,000; P = 1.00; 95% CI for risk difference [ipsilateral minus contralateral], −41 to +22 per 10,000). CONCLUSIONS: We found very few complications in patients who had an IV placed for surgery following a previous breast cancer surgery and no complications in those patients with IV placement ipsilateral with axillary node dissection. Avoidance of IV placement in the arm ipsilateral to breast cancer surgery is not necessary.

Effective delivery of cancer care via telehealth requires a planned care system that accounts for myriad patient, provider, and practice/cancer center resources before, during, and after the care episode. Telehealth is broadly defined as a method to have virtual, bidirectional communication between patients and providers. Telehealth can include methods such as audio-only, video-consultation, and tele-monitoring, which can occur in a synchronous, asynchronous, or blended format. The purpose of this review is to present common foundational principles for providing clinical cancer care via telehealth, followed by an overview of three distinct examples of comprehensive telehealth programs that have been developed to meet the needs of patients and families across the cancer trajectory, including survivorship, rehabilitation, and palliative care phases. The programs described are exemplars that were developed and implemented prior to the coronavirus pandemic, so they reflect many years of planning and evidence. Lessons learned include the need for ongoing patient support, clinician training, and cancer health system/practice programmatic considerations such as billing, scheduling, reimbursement, software, and hardware/platform security. Although the COVID-19 pandemic produced an explosive shift in regulations and implementation, sustainability of these changes may not be long-term. Nevertheless, a permanent shift in cancer care to include telehealth is likely here to stay.

9567 Background: Functional disability degrades cancer patients' quality of life, exhausts caregivers and incurs significant expense yet little is know of the factors that contribute to disablement or whether the impact of these factors differs across functional domains. Better understanding of the influence that symptoms, physical impairments, and disease characteristics exert on disablement is needed in order to develop service delivery models that preserve function. Methods: To identify factors that influence functional performance in community dwelling people with stage IV breast cancer we conducted a cross-sectional study in a tertiary medical center outpatient cancer clinic. A consecutive sample of 163 community-dwelling patients with stage IV breast cancer were administered self- and clinician-rated functional metrics covering multiple domains including overall functioning, mobility, and self care. Self report measures included the Medical Outcomes Study Physical Function Subscale (PF-10) and the Older Americans Resource Study (OARS) Activities of Daily Living (ADL) and Instrumental ADL (IADL) subscales, and clinician report measures included the Karnofsky Performance Scale (KPS) and the Functional Independence Measure (FIM) Total and Mobility scores. Pain and mental health were assessed through administration of the Brief Pain Inventory (BPI) and Mental Health Inventory-17 (MHI-17), respectively. Electronic medical record review provided cancer-related and demographic information. The presence of physical impairments was determined through a comprehensive musculoskeletal and neurological physical examination including the 6 minute walk test. Linear and ordinal logistic regression models were constructed with function metrics as dependent variables. Results: Total number of physical impairments, BPI scores, and the presence of pleural effusions were highly significant in all models (p<0.01). Exertional intolerance and age were associated with PF-10 and OARS-ADL scores (p<0.01), while the presence of a pre-morbid disability was associated compromised mobility. Conclusions: Potentially remediable factors; pain intensity, cumulative impairment burden and pleural effusions, degrade all functional domains in patients with stage IV breast cancer. No significant financial relationships to disclose.

7083 Background: Patients with Myelofibrosis (MF) suffer from significant fatigue, constitutional symptoms and splenomegaly (Mesa et. al. Cancer 2007) not improved by current therapy. The 6MWT measures functional status in cardio-pulmonary clinical trials. We undertook a prospective feasibility study of the 6MWT in MF patients for use in therapeutic clinical trials. Methods: MF patients (able to walk, normal vitals, not on a JAK2 inhibitor) were eligible. Baseline features and the MF symptom assessment form (MFSAF: Mesa et. al. Blood 2008) was administered. The 6MWT was administered in standardized fashion (American Thoracic Society: observed laps of a 30 - 35 meter long course, indoors, level, without encouragement), and then repeated for further validation. Results: Safety of the 6MWT: Fifty five MF patients were enrolled with only 2 patients (3%) stopping the 6MWT early secondary to fatigue. There were no adverse events attributable to undergoing the 6MWT in test subjects. Results of the 6MWT: Current results of our ongoing study demonstrate compared to age matched healthy volunteer controls, males with MF walk approximately 90 meters less and females with MF walk approximately 60 meters less (Table). Correlation of 6MWT Results to Patient Reported Symptoms (MFSAF): Results from the MFSAF demonstrated the fatigue (as assessed by the brief fatigue inventory (Medoza et. al. Cancer 1999) embedded in the MFSAF) showed patients with a higher BFI (i.e., more fatigued) had more impairment in the 6MWT than those with low BFI scores. Symptomatic burden as assessed by the MFSAF were typical for MF, correlation of individual symptom severity with 6MWT will require a larger trial for adequate power. Conclusions: The 6MWT can be safely performed in un-selected MF patients, and demonstrates a functional deficit compared to published controls. Validation of the ability of the 6MWT to measure functional improvements in MF patients as a response to novel therapy trials is planned. [Table: see text] No significant financial relationships to disclose.

Abstract Background: Myelofibrosis (MF) shortens survival but also compromises quality of life from disease associated splenomegaly and constitutional symptoms (fatigue, weight loss, night sweats, and bone pain). No current validated instrument of patient reported outcomes (PRO) captures the spectrum of MF associated symptoms. In an era of rapid development and testing of therapeutic agents which may impact the natural history and symptoms associated with MF (such as JAK2 inhibitors) a uniform and validated instrument for capturing the presence, severity (and potentially improvement) of MF symptoms is needed. We sought to develop and validate such an instrument, the myelofibrosis symptom assessment form (MFSAF). Methods: Based upon the results in our MF QOL survey (Cancer2007;109(1):68–76), we developed the MFSAF to assess fatigue (via the brief fatigue inventory (BFI-Cancer1999;85:1186)), additional symptoms were independently assessed for presence and severity on a scale from 0 (absent) to 10 (worst possible) for splenomegaly associated symptoms (early satiety, pain, inactivity, cough) night sweats, itching, bone pain, fever, unintentional weight loss as well as an estimate of overall quality of life. Additionally, patients provided feedback on the quality and nature of the MFSAF, and also completed for comparison validated instruments including the Memorial Symptom Assessment Scale (MSAS), the Insomnia Severity Index (ISI), and the Brief Pain Index. Physician input was included including their assessment of patient’s fatigue, spleen symptoms, and quality of life (blinded to patient’s responses) as well as clinical history, lab and exam findings. Results: MFSAF Results 34 MPD patients were enrolled (24 MF, 10 in the comparison group (4 polycythemia vera (PV), 6 essential thrombocythemia (ET)). the MFSAF was rated by patients as easy to understand (median score 1, range 0–6), and “addressed most of my symptoms” (median score 1, range 0–6) both on a scale of 0 (as good as possible to 10 as bad as possible). When asked if a symptom was not addressed (open ended response) no single symptom was named more than once. As we have previously reported fatigue was common with BFI scores (median 3.6 (0–10) for MF and 2.5 (range 0.2–3.8) for the ET/PV group (increasing BFI score associated with worsening fatigue) worse than median score of published “healthy” controls 2.2. Additional MF associated symptoms were captured well by the MFSAF with splenic, constitutional symptoms, and QOL (median 3 (range 0–7) MF, median 2 (0–3) ET/PV) documented easily and worse than ET/PV controls. Physicians estimation of QOL was excellent (median 3 (0–8) for MF, median 2 (0–4) for ET/PV). MFSAF Comparison to other Instruments: The MSAS demonstrated more adverse values for MF (than ET/PV) in the PSYCH (psychologic stress; mean-1.27 (STD DEV 0.80), PHYS (physical symptoms; mean 0.90 (STD DEV 0.53)), GDI (Global Distress Index mean-1.29 (STD DEV 0.77)) and a total MSAS symptom score (mean 0.85 (std dev (0.49)) comparable with advanced renal disease (PSYCH 0.99, PHYS 0.99, GDI 1.27, and MSAS of 0.81; J of Pall Med2007;10(6):1266), as well as advanced lung disease, AIDS, and various advanced malignancies. Individual, previously validated MSAS questions were all highly correlated (all p&lt;0.01) with MFSAF (in italic) counterparts including lack of energy (fatigue), cough (same), pain (both abdominal pain and bone pain), sweats (night sweats), itching (same), and weight loss (same). Further validation of pain measurements in the MFSAF came from comparison to the BPI where both individually the presence, and intensity of pain (both abdominal and bone) were highly correlated (all p&lt;0.01). Insomnia, not yet included in the MFSAF, was present in 68% and 63% of patients (MSAS and ISI, respectively). Additionally, problems with sexual interest, or activity, was noted in 35% of patients to the MSAS. Conclusions: Currently available instruments of PRO and symptoms are lengthy, and individually incomplete for assessing the presence and severity of the diverse nature of symptoms associated with MF. The proposed MFSAF, was comprehensive and well understood by patients and the results for the individual symptoms assessed were highly correlated with previously validated instruments for other conditions as well as with physicians perceptions of fatigue and QOL. The MFSAF, with the addition of questions regarding insomnia and sexuality, should be utilized in all trials of therapeutic agents in MF patients in which symptomatic improvements are an endpoint.

Context.— Autopsy rates have decreased dramatically despite providing important clinical information to medical practices and social benefits to decedents' families. Objective.— To assess the impact of an institutional Office of Decedent Affairs (ODA), a direct communication link between pathology and decedents' families, on hospital autopsy consent rates, autopsy-related communication, practitioner views, and next-of-kin experiences. Design.— A before and after study involving all hospital decedents whose deaths did not fall within the jurisdiction of the medical examiner's office from 2013 to 2018. A pathology-run ODA launched in May 2016 to guide next-of-kin through the hospital death process (including autopsy-related decisions) and serve as the next-of-kin's contact for any subsequent autopsy-related communication. Critical care and hematology/oncology practitioners were assessed for their autopsy-related views and decedents' next-of-kin were assessed for their autopsy-related experiences. Autopsy consent rates for non–medical examiner hospital deaths, autopsy-related communication rates, practitioner views on the role and value of autopsy, and next-of-kin autopsy experiences and decisions factors were compared prior to and after ODA launch. Results.— Autopsy consent rates significantly increased from 13.2% to 17.3% (480 of 3647 deaths versus 544 of 3148 deaths; P &lt; .001). There were significant increases in the rate of autopsy-related discussions and bereavement counseling provided to decedents' families. Practitioner views on the positive role of autopsy for any hospital death and those with advanced stage cancer also significantly increased. Next-of-kin indicated more consistent autopsy-related discussions with the potential benefits of autopsy discussed becoming key decision factors. Conclusions.— An ODA improves hospital autopsy consent rates, autopsy-related communication, providers' autopsy-related views, and next-of-kins autopsy experiences.

This article presents a clinical screening and referral framework to enable health care professionals to guide individuals with cancer to safe and effective exercise programs.

AbstractPurposeThe purpose of this analysis was to determine the cost‐effectiveness of a Collaborative Care Model (CCM)‐based, centralized telecare approach to delivering rehabilitation services to late‐stage cancer patients experiencing functional limitations.MethodsData for this analysis came from the Collaborative Care to Preserve Performance in Cancer (COPE) trial, a randomized control trial of 516 patients assigned to: (a) a control group (arm A), (b) tele‐rehabilitation (arm B), and (c) tele‐rehabilitation plus pharmacological pain management (arm C). Patient quality of life was measured using the EQ‐5D‐3L at baseline, 3‐month, and 6‐month follow‐up. Direct intervention costs were measured from the experience of the trial. Participants’ hospitalization data were obtained from their medical records, and costs associated with these encounters were estimated from unit cost data and hospital‐associated utilization information found in the literature. A secondary analysis of total utilization costs was conducted for the subset of COPE trial patients for whom comprehensive cost capture was possible.ResultsIn the intervention‐only model, tele‐rehabilitation (arm B) was found to be the dominant strategy, with an incremental cost‐effectiveness ratio (ICER) of $15 494/QALY. At the $100 000 willingness‐to‐pay threshold, this tele‐rehabilitation was the cost‐effective strategy in 95.4% of simulations. It was found to be cost saving compared to enhanced usual care once the downstream hospitalization costs were taken into account. In the total cost analysis, total inpatient hospitalization costs were significantly lower in both tele‐rehabilitation (arm B) and tele‐rehabilitation plus pain management (arm C) compared to control (arm A), (P = .048).ConclusionThe delivery of a CCM‐based, centralized tele‐rehabilitation intervention to patients with advanced stage cancer is highly cost‐effective. Clinicians and care teams working with this vulnerable population should consider incorporating such interventions into their patient care plans.

Introduction: With the expanding use of CAR-T cell therapy, which is associated with serious adverse effects (AEs), there is a need to characterize the patient's experience over time to guide patient/provider education, and help optimize symptom management. This study reports on longitudinal evaluation of patient-reported quality of life (QOL) and symptom burden of CAR-T cell therapy compared with established forms of cellular therapy i.e autologous stem cell transplant (autoSCT) and allogeneic SCT (alloSCT). Methods: Patients with hematologic malignancies were prospectively recruited in three cohorts: CAR-T, autoSCT and alloSCT. The primary endpoint was change in QOL from baseline, using the FACT-G questionnaire. Secondary endpoints were patient-reported AEs (PRO-AEs) using 7 items from the PRO-CTCAE and assessment of cognition/memory using the NeuroQOLv2 questionnaire. PRO-CTCAE data was graded using a composite score (combining frequency, severity, and interference) and rates, using a method adjusting for pre-existing baseline symptoms, were compared using Fisher's exact test. We also evaluated the time profile of PRO-AEs using the Toxicity over Time (ToxT) approach, a longitudinal approach to AE analysis (Thanarajasingam Lancet Onc 2016). Patients completed questionnaires at baseline, week 2 and monthly thereafter. Results: From 07/2018 to 06/2019, 93 patients were recruited (CAR-T: 20; autoSCT: 37; alloSCT: 36). At data cut-off, week 2 and months 1, 2 and 3 data were available in 74, 62, 46 and 35 patients, respectively. There was no difference in patient age across the 3 groups (median age 63, range 23-77; p=0.26). Baseline QOL by FACT-G total score (mean=83.4, SD=14.7; p=0.77), side effect bother by FACT-G GP5 (66/93 [71%] a little bit or less; p=0.72), activities and function (70/93 [75%] fairly normal activities or no limitations; p=0.68) and cognition by NeuroQOL t-score (mean=52.2, SD=8.13; p=0.39) were similar across 3 groups at baseline. The CAR-T group experienced significantly less worsening in QOL (FACT-G) than both autoSCT and alloSCT groups (Fig. 1a). Worsening in overall QOL nadired at week 2, after which QOL gradually returned to baseline in all groups. When comparing changes from baseline in overall QOL, statistically significant differences between groups were evident at week 2 (CAR-T vs autoSCT p&lt;0.001; vs alloSCT p&lt;0.001), month 1 (CAR-T vs autoSCT p=0.02; vs alloSCT p=0.003), month 2 (CAR-T vs autoSCT p=0.02; vs alloSCT p=0.001) and month 3 (CAR-T vs autoSCT p=NS; vs alloSCT p=0.03). Results for physical (Fig. 1b) and functional well-being (WB) were similar, with significantly less QOL worsening at week 2 in CAR-T vs autoSCT and alloSCT groups. The most common PRO-AEs (Table 1) in the CAR-T group were decreased appetite (59%), diarrhea (53%) and fatigue (44%). There was no statistically significant difference in the PRO-AEs between CAR-T and autoSCT groups. However, patients undergoing alloSCT had significantly higher proportion of PRO-AEs vs the CAR-T group, except for neuropathy and sad feelings. AutoSCT and alloSCT groups had significant worsening of FACT-G side effect bother (GP5) at week 2, which was significantly different from that of the CAR-T group, following which the side effect bother gradually returned to baseline. (Fig. 1c) This was the first application of ToxT to PRO-CTCAE data (graphs not shown). Bar charts of maximum grade frequency and stream plots of mean grade over time demonstrate that mouth sores, fatigue, diarrhea and decreased appetite peak at week 2 and improve by month 3, and are of lesser severity in the CAR-T vs autoSCT and alloSCT groups. The trajectory of maximum grade across all PRO-AEs was similar by group as overall side effect burden by FACT-G GP5. Heatmap visualization demonstrated significant intra-patient variability and allowed inspection of data completeness. No difference in cognition and memory was observed across the three groups over the first three months. (Fig. 1d) Conclusion: This study is the first to our knowledge to provide comprehensive PRO data comparing QOL, patient-reported AEs and cognition in CAR-T cell therapy vs. auto- and alloSCT, and the first application of ToxT to PRO-CTCAE data. Short-term QOL, including physical and functional WB domains was better in the CAR-T group vs. SCT groups. These data can serve as a guide for patient education and symptom management in CAR-T cell therapy. Co-senior authors: SKK & ACD Disclosures Paludo: Celgene: Research Funding; Celgene: Research Funding; Verily Life Sciences: Research Funding; Verily Life Sciences: Research Funding. Gertz:Johnson and Johnson: Speakers Bureau; Celgene: Consultancy; Appellis: Consultancy; Amyloidosis Foundation: Research Funding; DAVA oncology: Speakers Bureau; Physicians Education Resource: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Medscape: Consultancy, Speakers Bureau; Prothena Biosciences Inc: Consultancy; Teva: Speakers Bureau; Research to Practice: Consultancy; Annexon: Consultancy; Alnylam: Consultancy; International Waldenstrom Foundation: Research Funding; Ionis/Akcea: Consultancy; Spectrum: Consultancy, Research Funding; i3Health: Other: Development of educational programs and materials; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; Springer Publishing: Patents & Royalties. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Alnylam: Research Funding. Ansell:Trillium: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding. Bennani:Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Adicet Bio: Other: Advisory board; Adicet Bio: Other: Advisory board; Purdue Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Seattle Genetics: Other: Advisory board; Kite Pharma: Other: Advisory board; Adicet Bio: Other: Advisory board; Kite Pharma: Other: Advisory board; Bristol-Myers Squibb: Research Funding; Kite Pharma: Other: Advisory board; Purdue Pharma: Other: Advisory board. Kumar:Takeda: Research Funding; Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.