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A Panel Evaluation of the Changes in the General Public’s Social-Media-Following of United States’ Public Health Departments during COVID-19 Pandemic
Khokhar, Areej, Spaulding, Aaron , Niazi, Zuhair, Chanan‐Khan, Asher , Niazi, Shehzad K. , Sher, Taimur , Manochakian, Rami , Chanan-Khan, Asher, Niazi, Shehzad, Sher, Taimur , Spaulding, Aaron , Ailawadhi, Sikander

Journal of Primary Care & Community Health | March 2, 2021 | Volume: 12 | Issue: No issue available | Pages: No page available

10.1177/2150132721995450 | PMID 33648364 Get It

Importance: Social media is widely used by various segments of society. Its role as a tool of communication by the Public Health Departments in the U.S. remains unknown. Objective: To determine the impact of the COVID-19 pandemic on social media following of the Public Health Departments of the 50 States of the U.S. Design, Setting, and Participants: Data were collected by visiting the Public Health Department web page for each social media platform. State-level demographics were collected from the U.S. Census Bureau. The Center for Disease Control and Prevention was utilized to collect information regarding the Governance of each State’s Public Health Department. Health rankings were collected from “America’s Health Rankings” 2019 Annual report from the United Health Foundation. The U.S. News and World Report Education Rankings were utilized to provide information regarding the public education of each State. Exposure: Data were pulled on 3 separate dates: first on March 5th (baseline and pre-national emergency declaration (NED) for COVID-19), March 18th (week following NED), and March 25th (2 weeks after NED). In addition, a variable identifying the total change across platforms was also created. All data were collected at the State level. Main Outcome: Overall, the social media following of the state Public Health Departments was very low. There was a significant increase in the public interest in following the Public Health Departments during the early phase of the COVID-19 pandemic. Results: With the declaration of National Emergency, there was a 150% increase in overall public following of the State Public Health Departments in the U.S. The increase was most noted in the Midwest and South regions of the U.S. The overall following in the pandemic “hotspots,” such as New York, California, and Florida, was significantly lower. Interesting correlations were noted between various demographic variables, health, and education ranking of the States and the social media following of their Health Departments. Conclusion and Relevance: Social media following of Public Health Departments across all States of the U.S. was very low. Though, the social media following significantly increased during the early course of the COVID-19 pandemic, but it still remains low. Significant opportunity exists for Public Health Departments to improve social media use to engage the public better.
EUS-guided gastroenterostomy versus enteral stenting for gastric outlet obstruction: Systematic review and meta-analysis
Khan, Shahab R. , Shah, Aun R. , Ramai, Daryl , Bhogal, Neil, Dhindsa, Banreet, Kassab, Lena L., Singh, Shailendra , Ponnada, Suresh, Nguyen, Andrew K. L., McDonough, Stephanie, Adler, Douglas G., Chandan, Saurabh , Mohan, Babu P. , Bilal, Mohammad , Adler, Douglas G.

Endoscopy International Open | February 23, 2021 | Volume: 09 | Issue: 03 | Pages: E496-E504

10.1055/a-1341-0788 | PMID 33655056 Get It

Abtract Background and study aims Endoscopic and surgical techniques have been utilized for palliation of gastric outlet obstruction (GOO). Enteral stenting (ES) is an established technique with high clinical success and low morbidity rate. Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is a novel approach that aims to provide sustained palliation of GOO. We conducted a comprehensive review and meta-analysis to evaluate the effectiveness in terms of clinical and technical success, as well as the safety profile of EUS-GE and ES. Methods We searched multiple databases from inception through July 2020 to identify studies that reported on safety and effectiveness of EUS-GE in comparison to ES. Pooled rates of technical success, clinical success, and adverse events (AEs) were calculated. Study heterogeneity was assessed using I2% and 95 % confidence interval. Results Five studies including 659 patients were included in our final analysis. Pooled rate of technical and clinical success for EUS-GE was 95.2 % (CI 87.2-.98.3, I2 = 42) and 93.3 % (CI 84.4–97.3, I2 = 59) while for ES it was 96.9 % (CI 90.9–99, I2 = 64) and 85.6 % (CI 73–92.9, I2 = 85), respectively. Pooled rate of re-intervention was significantly lower with EUS-GE i. e. 4 % (CI 1.8–8.7, I2 = 35) compared to ES, where it was 23.6 % (CI 17.5–31, I2 = 35), p = 0.001. Pooled rates of overall and major AEs were comparable between the two techniques. Conclusion EUS-GE is comparable in terms of technical and clinical effectiveness and has a similar safety profile when compared to ES for palliation of GOO.
Bending the Curve in Cardiovascular Disease Mortality
Goff, David C. , Khan, Sadiya S. , Lloyd‐Jones, Donald M. , Arnett, Donna K. , Carnethon, Mercedes R. , Labarthe, Darwin R. , Loop, Matthew Shane , Luepker, Russell V. , McConnell, Michael V. , Mujahid, Mahasin S. , Roger, Véronique L. , Rosamond, Wayne D. , Sidney, Stephen , Wei, Gina S., Wright, Janet S. , Lloyd-Jones, Donald M , Arnett, Donna K , Khan, Sadiya S , Mensah, George A. , O’Flaherty, Martín , Prabhakaran, Dorairaj

Circulation | February 22, 2021 | Volume: 143 | Issue: 8 | Pages: 837-851

10.1161/circulationaha.120.046501 | PMID 33617315 Get It

More than 40 years after the 1978 Bethesda Conference on the Declining Mortality from Coronary Heart Disease provided the scientific community with a blueprint for systematic analysis to understand declining rates of coronary heart disease, there are indications the decline has ended or even reversed despite advances in our knowledge about the condition and treatment. Recent data show a more complex situation, with mortality rates for overall cardiovascular disease, including coronary heart disease and stroke, decelerating, whereas those for heart failure are increasing. To mark the 40th anniversary of the Bethesda Conference, the National Heart, Lung, and Blood Institute and the American Heart Association cosponsored the “Bending the Curve in Cardiovascular Disease Mortality: Bethesda + 40” symposium. The objective was to examine the immediate and long-term outcomes of the 1978 conference and understand the current environment. Symposium themes included trends and future projections in cardiovascular disease (in the United States and internationally), the evolving obesity and diabetes epidemics, and harnessing emerging and innovative opportunities to preserve and promote cardiovascular health and prevent cardiovascular disease. In addition, participant-led discussion explored the challenges and barriers in promoting cardiovascular health across the lifespan and established a potential framework for observational research and interventions that would begin in early childhood (or ideally in utero). This report summarizes the relevant research, policy, and practice opportunities discussed at the symposium.
Fibrillary glomerulonephritis or complement 3 glomerulopathy: a rare case of diffuse necrotising crescentic glomerulonephritis with C3-dominant glomerular deposition and positive DNAJB9
Baker, Lyle W. , Khan, Mahnoor, Cortese, Cherise , Aslam, Nabeel , Baker, Lyle Wesley

BMJ Case Reports | February 18, 2021 | Volume: 14 | Issue: 2 | Pages: e239868

10.1136/bcr-2020-239868 | PMID 33602773 Get It

Fibrillary glomerulonephritis (FGN) and complement 3 glomerulopathy (C3G) are rare forms of glomerulonephritis with distinct aetiologies. Both FGN and C3G can present with nephritic syndrome. FGN is associated with autoimmune disease, dysproteinaemia, malignancy and hepatitis C infection. C3G is caused by the unregulated activation of the alternative complement pathway. We present a rare case of diffuse necrotising crescentic glomerulonephritis with dominant C3 glomerular staining on immunofluorescence—consistent with C3G—but electron microscopy (EM) findings of randomly oriented fibrils with a mean diameter of 14 nm and positive immunohistochemistry for DNAJB9—suggestive of FGN. To the best of our knowledge, this is the first reported case of FGN to show dominant C3 glomerular deposits. This case report reaffirms the utility of EM in the evaluation of nephritic syndrome and highlights the value of DNAJB9—a novel biomarker with a sensitivity and specificity near 100% for FGN.
Addition of Lenalidomide to R-CHOP Improves Outcomes in Newly Diagnosed Diffuse Large B-Cell Lymphoma in a Randomized Phase II US Intergroup Study ECOG-ACRIN E1412
Nowakowski, Grzegorz S. , Hong, Fangxin , Scott, David W. , Macon, William R. , King, Rebecca L. , Wagner‐Johnston, Nina D. , Wade, James L. , Nagargoje, Gauri G., Reynolds, Chris, Cohen, Jonathon B. , Amengual, Jennifer E. , Richards, Kristy L. , Little, Richard F. , Leonard, John P. , Friedberg, Jonathan W. , Kostakoglu, Lale , Wade, James L , Cohen, Jonathon B , Khan, Nadia , Amengual, Jennifer E , Little, Richard F , Kostakoglu, Lale , Kahl, Brad S , Witzig, T.E. , Scott, David W , Hong, Fangxin , Habermann, Thomas M. , Casulo, Carla , Khan, Nadia , Kahl, Brad S. , Witzig, Thomas E.

Journal of Clinical Oncology | February 8, 2021 | Volume: 39 | Issue: 12 | Pages: 1329-1338

10.1200/jco.20.01375 | PMID 33555941 Get It

PURPOSE Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell–like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL. PATIENTS AND METHODS Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS). RESULTS Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell–like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1. CONCLUSION In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL.
A Systematic Review of High Dose Chemotherapy with Autologous Transplantation in Secondary CNS Lymphoma
Abdullah, Sikander, Naqvi, Syeda Aiman Gohar, Zaidi, Fatima Zia , Tayyeb, Muhammad , Zaidi, Khadija Zia, Haider, Mobeen Z. , Khalid, Farhan , Jaan, Ali , Ehsan, Amrat , Anwer, Faiz , Anwer, Faiz , Abdullah, Syed Maaz , Sana, Muhammad Khawar , Ehsan, Hamid , Badar, Talha

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 14-14

10.1182/blood-2020-143235 Get It

Introduction: Secondary Central Nervous System Lymphoma (SCNSL) is the spread of a lymphoma to the CNS, the primary focus of which is situated elsewhere in the body. Most commonly, it is a non-Hodgkin lymphoma which either presents as a CNS involvement due to systemic relapse or progression, or as an isolated relapse in the CNS despite systemic remission. Traditionally, it has been treated by intrathecal or systemic chemotherapy and/or WBRT (Whole-brain radiation therapy) but recently, the use of high-dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) has shown encouraging results. We present a systematic review of literature displaying the treatment outcomes of HDT/ASCT in SCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on July 08 2020 on PubMed, Cochrane Library and Clinicaltrials.Gov by using the relevant MeSH terms of high-dose chemotherapy, autologous stem cell transplantation, CNS lymphoma, efficacy and safety. Following screening by 2 reviewers, we selected 12 published studies (n=353) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 232/353 patients eventually underwent sequential HDT+ASCT who were evaluable for treatment response out of which 190 patients had SCNSL (see table 1). Carmustine (BCNU) based HDT: BCNU based regimens have been the most extensively studied HDT among SCNSL patients (n=81). Korfel et al. in a phase 2 trial (2013, n=30) used HDT combination of BCNU, thiotepa and etoposide followed by ASCT in SCNSL patients. No patient was given whole brain radiation therapy (WBRT). The results yielded a PR of 8%, CR of 63% and 2-year OS of 63%. 1 toxicity related mortality (TRM) was noted and >grade 4 adverse effects included infection (4%) and stomatitis (13%). Ferreri et al. (2015, n=38) in a phase 2 trial use HDT with BCNU plus thiotepa on 38 patients 20 of whom underwent subsequent ASCT. The results showed CR of 100%, event free survival (EFS) of 40% ±9% and OS of 41% ±8% at 5 years with four patients suffering TRM. Thiotepa, busulfan and cyclophosphamide (TBC) based HDT: The combination based on TBC has been a popular option for SCNSL patients (n=53). In a retrospective analysis by Welch et al. (2014, n=17), TBC combination followed by sequential ASCT was studied in both primary and SCNSL patients (primary malignancy being diffuse large B-cell lymphoma) and the collective results showed complete response (CR) of 100%, PFS of 93% (95% CI: 61-99%) and OS of 93% (95% CI: 61-99%) at 3 years. In addition to the excellent efficacy response, no TRM or grade 4 toxicities were documented. Chen et al. (2015, n=12) in a phase 2 trial used HDT with rituximab and TBC (R-TBC) combination followed by ASCT rescue in 12 SCNSL patients. At 2 years, the progression free survival (PFS) was 51% (95% CI: 18-77%) and overall survival (OS) was 83% (95% CI: 48-96%). Two patients developed neurotoxicity and one TRM was recorded. Methotrexate (MTX) based HDT: MTX based combinations have also been widely used as HDT preceding ASCT in SCNSL patients (n=51). Fischer et al. (2008, n=20) studied HDT of MTX plus ifosfamide (IFO) in a retrospective analysis which showed PR of 30%, CR of 60% and median OS of 8.7 months and two TRM (due to sepsis in neutropenia) in SCNSL patients. Lee et al. (2015, n=31) in a prospective cohort study evaluated HDT with MTX based multidrug combination with ASCT in SCNSL patients which yielded a PR of 41.6%, CR of 50% and OS of 9 months (95% CI: 5-12 months). Five patients had suffered TRM. Conclusion: The combination of HDT with ASCT has yielded promising treatment outcomes both in terms of favorable efficacy rates and reduced rates of toxicity in SCNSL patients proving to be a comparable alternative to traditionally used chemo-radiation. However, the data at present is limited to few phase 2 trials with some being displayed collectively with data of primary CNS lymphoma patients. There is an increased need to carry out randomized phase 3 trials exclusively on SCNSL patients to better predict the efficacy and safety profile of HDT/ASCT in these patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.
Racial Disparities and Their Impact on Knowledge, Behavioral Patterns, and Preferences Towards Participation in Clinical Trials Among Cancer Patients
Ailawadhi, Meghna, Abdulazeez, Mays F , Alegria, Victoria R., Sher, Taimur , Paulus, Aneel , Chanan‐Khan, Asher , Paulus, Aneel , Bojanini, Leyla , Roy, Vivek , Manochakian, Rami , Ailawadhi, Sikander

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 39-40

10.1182/blood-2020-140390 Get It

Background: Clinical trials are critical to drug development and the formulation of evidence-based guidelines which are essential to providing crucial and often life-saving treatment to cancer patients. Clinical trial participation is very poor in the United States overall, with a dismal representation of racial minorities. While this has been a focus of several efforts focused on education, targeted enrollment etc., there is a lack of understanding of the patient's knowledge and preferences, and how that may be shaping their decision to consider participation in clinical trials. We undertook a patient-reported survey to explore these factors and understand any underlying disparities. Methods: A 15-question paper-based anonymous questionnaire addressing the cancer patient's knowledge about their disease and clinical trials, as well as factors that may shape their understanding of, or may be barriers to their participation in clinical trials was used. This was administered to adult patients with lymphoid malignancies at the Mayo Clinic in Florida. Categorical and continuous variables between white and minority respondents were compared using the Chi-square test and U Mann Whitney with a significance level of 0.05. Results: The survey was completed by 203 cancer patients. Of these, 3 patients did not report race and ethnicity and so responses from 200 patients were included in the final analysis. Of the respondents, 73% (n=146) were white and 27% (n=54) were minorities. Whites were older than minorities, although not statistically significant (median 67 vs. 61.5 yrs, p=0.06). Minority patients had lower education level with 41% having ≤high school education as compared to 16% whites (p<0.001). Majority of white patients (53%) reported their physicians as the highest ranked source of information for cancer vs. 33% minority patients (p=0.01). Other sources of information explored were internet, nurses, family/friends, books/flyers or other patients. A higher number of white patients reported treatment and its side effects to be the topic of most importance to them at the time of cancer diagnosis as compared to minorities (33% vs. 15%, p=0.01). Similarly, prognosis was more important for a higher number of whites than minorities (21% vs. 15%, p=0.03). Understanding of the diagnosis and financial impact were also explored but not found to have any significant difference. Understanding their treatment and long-term treatment plan was the most frequent knowledge gap reported by whites (81%) vs. minorities (54%, p=0.004). Minorities had several knowledge gap areas (understanding the diagnosis, treatment, side effects, long-term treatment plan, financial impact, survival) more evenly distributed. Regarding clinical trials, minorities were more likely to agree that clinical trials were of benefit for patients (42% vs. 28%, p=0.05) and that in a clinical trial the experimental drug always works better than the one it is being compared to (65% vs. 38%, p<0.001). Minority patients were less likely to agree to participating in clinical trials just based on their doctor's recommendation and judgement (83% vs. 93%, p=0.03). A higher number of minority patients felt that pharmaceutical companies have a big influence on the result of a clinical trial (83% vs. 65%, p=0.01). Fear of not benefiting from clinical trials was the reason for not participating among a higher number of whites (36% vs. 19%, p=0.02) while minorities more frequently reported fear of being a guinea pig (22% vs. 14%) and fear of financial burden (17% vs. 8%) although these were not statistically significant. Conclusions: Racial disparities exist at various aspects of cancer-related knowledge resources, gaps and needs. Minorities have more widespread knowledge gaps and depend on more resources for cancer-related knowledge, which may affect their clinical trial participation and preferences. There appears to be mistrust and misinformation guiding minority patient's understanding, leading to more widespread fears of clinical trials. Knowledge gaps and misinformation needs to be addressed in order to achieve higher participation in clinical trials in general, and among minority patients in particular. Disclosures Manochakian: AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Guardant health: Membership on an entity's Board of Directors or advisory committees; Novocure: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Ailawadhi:Phosplatin: Research Funding; Medimmune: Research Funding; BMS: Research Funding; Cellectar: Research Funding; Pharmacyclics: Research Funding; Janssen: Research Funding; Takeda: Honoraria; Amgen: Research Funding; Celgene: Honoraria.
Open Label, Multicenter, Dose-Escalation/ Expansion Phase Ib Study to Evaluate Safety and Activity of BET Inhibitor RO6870810 (RO), Given As Monotherapy to Patients (pts) with Advanced Multiple Myeloma
Htut, Myo , Popat, Rakesh , Liedtke, Michaela , Laubach, Jacob P. , Gasparetto, Cristina , Chanan‐Khan, Asher , DeMario, Mark , Nueesch, E., Chesné, Evelyne , Franjkovic, Izolda , Kornacker, Martin , Ramasamy, Karthik , Nooka, Ajay K. , Quach, Hang , Popat, Rakesh , Tuchman, Sascha Alexander , Hertzberg, Mark , Lechner, Katharina , Cho, Hearn Jay

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 12-14

10.1182/blood-2020-136392 Get It

Introduction Multiple myeloma (MM), relapsed or refractory (R/R) to standard of care therapies, represents a treatment indication with a significant unmet clinical need. Transcriptional activation of c-MYC through bromodomain and extra-terminal (BET) proteins contributes to the malignant phenotype of the disease. RO is a novel thienodiazepine, small molecule, non-covalent inhibitor of the BET family of bromodomains. Preclinical studies with BET inhibitors have demonstrated significant single agent in vivo activity in myeloma, accompanied by down-regulation of MYC and MYC target gene expression. We report results of a monotherapy phase 1b study of RO in R/R MM (NCT03068351). Methods Eligible pts with R/R MM included those treated with at least three prior lines of multiple myeloma therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double-refractory to a proteasome inhibitor and an immunomodulatory agent. Primary refractory myeloma pts were only allowed in the dose escalation portion of the study. In the dose escalation (part I), pts received subcutaneous (SC) escalating doses of RO (0.30-0.65 mg/kg) in a standard 3 + 3 design on days 1 - 14 of 21-day cycles to determine both the maximum tolerated dose (MTD) and recommended dose (RD). In the expansion cohort (part II), pts received RO as monotherapy at the RD level. Primary endpoint was safety (DLT, MTD, RD) and secondary endpoints included evaluation of pharmacodynamics (CD11b expression) and preliminary efficacy assessments based on IMWG criteria. Results Between June 2017 and April 2019, a total of 24 pts were enrolled in the US, the UK and Australia. 13 pts were enrolled in the dose escalation and 11 pts in the expansion part. The median age of pts was 65.5 years (range: 46 - 82 years). The study population was heavily pretreated with a median of 6 (3-9) prior therapies. Pts were refractory to immunomodulatory drugs (63%), proteasome inhibitors (46%), both (46%), or daratumumab (42%). 57 total cycles were administered, with a median of 2 (1-6) cycles per patient (pt). Two DLTs occurred in one pt in the 0.65 mg/kg cohort (thrombocytopenia grade 4, angina pectoris grade 3). The recommended dose is 0.65 mg/kg. Grade 3 treatment emergent AEs in ≥ 5% of pts were thrombocytopenia (11 pts [45.8%]), anemia (7 pts [29.2%]), fatigue (3 pts [12.5%]), injection site reaction, malaise, decreased appetite, and hyponatremia (2 pts [8.3%] each). 3 pts (12.5%) experienced a total of 4 AEs leading to discontinuation of the study treatment; these AEs were left ventricular dysfunction, fatigue, sepsis, and staphylococcal bacteremia (the latter two AEs occurred in the same pt). A total of 8 deaths (33.3%) were reported in the study, all as a consequence of progressive disease. The best overall response recorded was partial response in 4 pts (16.7 %), 3 of whom having received prior daratumumab. One pt experienced a minimal response, and stable disease was reported in 12 out of 24 (50%). There was no evidence for a dose-related increase in efficacy, though data are very limited (Table). Responses obtained during treatment with RO6870810 were short-lived and lasted for appr. 6 weeks. As evidence of target engagement, pharmacodynamic profiling demonstrated decreases in CD11b levels in peripheral blood mononuclear cells (Figure). Conclusions Treatment of MM pts with the BET inhibitor RO as monotherapy resulted in a high incidence of cytopenias, especially grade 3-4 thrombocytopenia and grade 3 anemia. However, none of these events led to study drug discontinuation. Cytopenias are a known side effect of BET inhibitors, with thrombocytopenia frequently reported as a DLT in various pt populations. Pts with NUT carcinoma, other solid tumors, or diffuse large B-cell lymphoma treated in the First in Man trial of RO had a low rate of cytopenias, indicating that the underlying disease and the extensive pre-treatment in MM may play a role in their occurrence (publication submitted). In this heavily pretreated R/R MM population, we have established 0.65 mg/kg as the recommended monotherapy dose. Pharmacodynamics effects were evident at this dose, but as monotherapy in this R/R MM cohort, response rates were low and less durable. Future drug combination approaches may result in an improved benefit / risk ratio. Disclosures Ramasamy: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria. Nooka:Adaptive Technologies: Consultancy, Honoraria; Oncopeptides: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy; GlaxoSmithKline: Consultancy, Honoraria, Other: Personal Fees: Travel/accomodations/expenses, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Karyopharm Therapeutics, Adaptive technologies: Consultancy, Honoraria, Research Funding. Quach:Amgen, Celgene, karyopharm, GSK, Janssen Cilag, Sanofi.: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Consultancy; GlaxoSmithKline, Karyopharm, Amgen, Celgene, Janssen Cilag: Honoraria; Amgen, sanofi, celgene, Karyopharm, GSK: Research Funding. Htut:City of Hope Medical Center: Current Employment. Popat:AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Liedtke:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Caelum: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees. Tuchman:Caelum: Honoraria; Sanofi: Honoraria, Research Funding; Amgen: Research Funding; Janssen: Research Funding; Oncopeptides: Consultancy; Roche: Research Funding; Karyopharm: Honoraria, Research Funding; Celgene: Honoraria, Research Funding, Speakers Bureau. Hertzberg:Gilead: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Demario:BioNTech SE: Current Employment, Current equity holder in publicly-traded company; Hoffmann-La Roche Ltd.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Nueesch:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Chesne:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Franjkovic:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company. Lechner:Roche Diagnostics GmbH: Current Employment, Current equity holder in publicly-traded company. Kornacker:Hoffmann-La Roche Ltd.: Current Employment, Current equity holder in publicly-traded company.
Daratumumab Plus Lenalidomide and Dexamethasone (DRd) Compared to Daratumumab Plus Pomalidomide and Dexamethasone (DPd) in Relapsed Lenalidomide-Exposed or Refractory Multiple Myeloma (MM) Patients: The Mayo Clinic Experience
Abdulazeez, Mays F , Sher, Taimur , Alegria, Victoria R., Warsame, Rahma , Larsen, Jeremy T. , Kourelis, Taxiarchis , Kapoor, Prashant , Hayman, Suzanne R. , Reeder, Craig B. , Agrawal, Arshi, Chanan‐Khan, Asher , Moustafa, Muhamad Alhaj , Parrondo, Ricardo D , Roy, Vivek , Gonsalves, Wilson I. , Fonseca, Rafaël , Buadi, Francis K. , Dingli, David , Ailawadhi, Sikander

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 1-2

10.1182/blood-2020-139929 Get It

Introduction: Daratumumab (D) is an anti-CD38 monoclonal antibody, used frequently in combination with immunomodulatory drugs (IMiDs), lenalidomide (Len) and pomalidomide (Pom). There are no studies comparing DRd to DPd in Len-exposed or refractory multiple myeloma (MM). We present the Mayo Clinic experience of DPd and DRd utilization and outcomes. Methods: We identified consecutive MM pts who received D, between 1/2015 and 4/2019 at Mayo Clinic. We included pts who were exposed (at least one full cycle, 21/28 days) or refractory (progression on full dose or maintenance Len during treatment or within 60 days of stopping Len) to Len prior to D and received 1 to 4 prior lines of therapy. Only Pts who received DRd and DPd were included. Results: Out of 411 evaluable pts 162 met the inclusion criteria; 67 were Len exposed, but not refractory and 95 were Len refractory. Pts' characteristics are shown in Table 1. DRd was used in 76 (47%) and DPd in 86 (53%) pts. Majority of pts (105; 65%) received DPd or DRd in the 2nd or 3rd line and 104 pts (64%) are still alive. In Len refractory pts, the median time from last dose of Len to D initiation was 1 mths (interquartile range 0-6.5). Seventy pts (43%) had high-risk cytogenetics (HR). Only 11 pts (7%) underwent autologous hematopoietic cell transplant after DPd or DRd regimen. There was no significant difference between pts who received DRd and DPd in terms of age (>65 years), gender, race, proportion exposed or refractory to Bortezomib, number of prior lines of treatment (>2), or HR status (p>0.05 for all). Pts who received DPd were 4 times more likely to be Len refractory compared to pts who received DRd, p=0.0008. Median follow up time for the whole cohort from initial diagnosis was 92 mths (CI 95%; 79.5-107), while from D start date was 30 mths (CI 95%; 27-34). Median PFS for the whole cohort was 21 mths (CI 95%; 15-25) and median OS was 138 mths (CI 95%; 111-193). In Len exposed but not refractory pts, n=67, the overall response rate (ORR) was 82% in the DRd group compared to 68% in the DPd group, p=0.2. There was no difference in median PFS; 25.5 mths (CI 95%; 23-NR) for DRd compared to 25 mths (CI 95%; 5-NR) for DPd, p=0.37. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 138-NR) and 145.5 mths (CI 95%; 70-NR), respectively, p=0.06. In the 48 Len exposed but refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 39 mths (CI 95%; 23-NR) for DRd compared to 21 mths (CI 95%; 3-NR) for DPd, p=0.11. Similarly, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; NR-NR) and 145.5 mths (CI 95%; 36-NR), respectively, p=0.13. In Len refractory pts only, n=95, the ORR was 84% in the DRd group compared to 58% in the DPd group, p=0.009. There was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 9 mths (CI 95%; 5-15) for DPd, p=0.18. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 78-NR) and 106 mths (CI 95%; 66-183), respectively, p=0.5. In the 57 Len refractory pts who received DRd or DPd in 2nd or 3rd line, there was no difference in median PFS; 25 mths (CI 95%; 13-32) for DRd compared to 13 mths (CI 95%; 5-NR) for DPd, p=08. Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 69-NR) and 105 mths (CI 95%; 47-NR), respectively, p=0.35. In the 16 Len exposed but not refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, the median PFS was better in the DRd group; 24.4 mths (CI 95%; 12-NR) compared to 3.3 mths (CI 95%; 1.9-27.5) for DPd, p=0.0093. However, there was no difference in median OS for DRd compared to DPd; NR mths (CI 95%; 51-NR) and NR mths (CI 95%; 18-NR), respectively, p=0.13. In the 29 Len refractory pts with HR MM who received DRd or DPd in 2nd or 3rd line, there was no statistically significant difference in median PFS; 18 mths (CI 95%; 6-43) for DRd compared to 6 mths (CI 95%; 4-13) for DPd, p=0.22.Similarly, there was no difference in median OS for DRd compared to DPd; 103 mths (CI 95%; 47-NR) and 53 mths (CI 95%; 26-105), respectively, p=0.2. Conclusions: D+IMiD regimens after prior Len exposure/refractoriness are commonly used in real-world, despite the lack of data from prospective clinical trials. Combining D with IMiDs in Len exposed or refractory pts is efficacious, whether the IMiD is Len or Pom. Our study shows that regardless of prior Len use, DRd is at least equivalent to DPd. Prospective studies should be done to confirm these observations. Disclosures Alhaj Moustafa: Acrotech: Consultancy. Larsen:Janssen Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Kapoor:Janssen: Research Funding; GlaxoSmithKline: Research Funding; Cellectar: Consultancy; Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria, Research Funding; Sanofi: Consultancy, Research Funding. Fonseca:Amgen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Takeda: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy; Sanofi: Consultancy; Merck: Consultancy; Juno: Consultancy; Kite: Consultancy; Aduro: Consultancy; OncoTracker: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy; GSK: Consultancy; AbbVie: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Dingli:Karyopharm Therapeutics: Research Funding; Rigel: Consultancy; Bristol Myers Squibb: Research Funding; Millenium: Consultancy; Sanofi-Genzyme: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Apellis: Consultancy. Ailawadhi:Celgene: Honoraria; Amgen: Research Funding; Takeda: Honoraria; Janssen: Research Funding; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding.
Myocarditis associated with Covid-19 disease: a systematic review of published Case reports and Case series
Rathore, Sawai Singh , Rojas, Gianpier Alonzo , Sondhi, Manush , Pothuru, Suveenkrishna , Pydi, Reshma , Kancherla, Neeraj , Ahmed, Noman Khurshid, Shah, Jill, Tousif, Sohaib , Baloch, Unaiza Tariq, Wen, Qingqing , Singh, Romil

No container title available | February 1, 2021 | Volume: No volume available | Issue: No issue available | Pages: No page available

10.22541/au.161219538.89676033/v1 Get It

Background: Covid-19 is an extremely contagious illness caused by the severe acute respiratory syndrome (SARS-CoV-2) virus. Although this disease primarily involves pulmonary tissue, rapidly advancing research has established cardiac involvement in Covid-19 patients. Objective: This systematic review article aimed to compile and illustrate clinical characteristics, diagnostic findings, management, and outcomes manifesting in myocarditis linked with Covid-19. Methods: A literature search was accomplished for published eligible articles with MEDLINE/PubMed and Embase databases. All eligible case reports and case series were included from around the world without any language restrictions. For this review, inclusion criteria were laboratory-confirmed SARS-CoV-2 infection cases reporting a diagnosis of acute myocarditis. Results: Data from 41 studies describing myocarditis in 42 Covid-19 patients was obtained. The median age of these patients was 43.4 years, with 71.4% of them being male. Fever was the most prevalent presenting symptoms seen in 57% of patients. Hypertension was the most pervasive comorbidity accompanying these patients. Cardiac biomarkers troponin and Brain natriuretic peptide (BNP) were raised in almost 90% and 87% of patients, respectively. Electrocardiogram findings were Non-specific and included ST-segment and T-wave changes. The most prevalent histopathological feature appreciated was diffuse lymphocytic inflammatory infiltrates. Antivirals and corticosteroids were the most frequently used medications. About 38% of patients also needed vasopressor assistance. Out of 42 patients, 67% recovered, and eight died. Conclusion: Due to the risk of a sudden worsening of patients conditions and myocarditis association with considerable mortality and morbidity, a knowledge of this cardiac complication of Covid-19 disease is crucial for healthcare professionals.