Preliminary results from phase 2 of CC-92480- MM- 001: Mezigdomide plus dexamethasone in relapsed/refractory multiple myeloma (RRMM)

In phase 1 of CC-92480- MM- 001 (NCT03374085), the recommended phase 2 dose (RP2D) of mezigdomide plus dexamethasone (MEZI-d) was selected at 1 mg once daily for 21/28 days. Here we report preliminary results from the MEZI-d dose-expansion cohort in patients with heavily pretreated RRMM. Key eligibility criteria were: RRMM;>=3 prior lines of therapy;disease progression <=60 days of last myeloma therapy;refractoriness to lenalidomide/pomalidomide, a proteasome inhibitor, a glucocorticoid, and an anti-CD38 monoclonal antibody. Oral mezigdomide 1 mg was given on days 1-21 of each 28-day cycle, plus weekly dexamethasone (40 mg;20 mg if >75 years of age). Primary objective was to evaluate efficacy (overall response rate [ORR]);secondary objectives included safety/tolerability and additional efficacy assessments. Pharmacodynamics was an exploratory objective. As of 16/Sep/2022, 101 patients had received MEZI-d at the RP2D. Median age was 67 (range 42-85) years, median time since initial diagnosis was 7.4 (1.1-37.0) years;39.6% of patients had plasmacytomas and 37/101 patients had high-risk cytogenetics (56/101 not evaluable). Median number of prior regimens was 6 (3-15);prior therapies included stem cell transplantation (77.2%) and anti-BCMA therapy (29.7%). All patients were refractory to last myeloma regimen and triple-class refractory. Median follow-up was 7.5 (0.5-21.9) months, with a median of 4 (1-20) cycles;10.0% of patients continued treatment;progressive disease was the main reason for discontinuation (60.4%). ORR was 40.6% for all patients. Whilst data are not mature yet, median PFS was 4.4 (95% CI 3.0-5.5) months and median duration of response was 7.6 (95% CI 5.4-9.5) months. ORR was 30.0% in patients with plasmacytomas (N = 40) and 50.0% in patients with prior anti-BCMA therapy (N = 30). Ninety-one (91.1%) patients experienced a grade 3/4 treatment-emergent adverse event (TEAE). Most frequent hematologic grade 3/4 TEAEs were neutropenia (75.2%), anaemia (35.6%), and thrombocytopenia (27.7%);34.7% of patients had grade 3/4 infections, including grade 3/4 pneumonia (15.8%) and COVID-19 (7.0%). Occurrence of other grade 3/4 non-hematologic TEAEs was generally low. Due to TEAEs, 76.2% and 29.7% of patients had mezigdomide dose interruptions and reductions, respectively;90.1% of patients discontinued mezigdomide. Mezigdomide induced substrate degradation and increases in activated and proliferating T cells in patients, including those directly refractory to pomalidomide-based therapies. MEZI-d had a manageable safety profile with encouraging efficacy in patients with triple-class refractory RRMM, including patients with prior BCMA-targeted therapies. These results strongly support the continued development of mezigdomide in MM, and especially in combination.

ACAPELLA: Real-World Experience with Ocrelizumab: An Observational Study Evaluating Safety in Patients with Relapsing and Progressive MS, Late Breaking Data

Introduction: Ocrelizumab (OCR) is a humanized monoclonal antibody therapy targeting CD20+ B cells for relapsing remitting (RRMS) and primary progressive MS (PPMS). The ACAPELLA trial is a prospective study with a primary objective of assessing OCR-associated adverse events (AEs) in a real-world MS population. ACAPELLA includes patients who would have been exempted from the phase II & III clinical trials because of pre-existing conditions such as a prior history of malignancy, prior immunosuppressive treatment, and advanced age and/or disability. Objective(s):To document the frequency of infections, incidence of cancer and other adverse events in patients treated with ocrelizumab at the Elliot Lewis Center (ELC). Aim(s): We sought to compare the frequency of adverse events in patients similar to those in the pivotal trials with those who would have been excluded based on age > 55, higher EDSS scores, and/ or pre-existing medical conditions. Method(s): The study includes all subjects treated with OCR at the (ELC) since its release in March 2017. Assessments include EDSS, brain MRI, mammograms (standard of care), collection of medical history including prior serious or recurrent infections, history of malignancy and exposure to immunosuppressive treatment, JCV index, and CD19 count. Result(s): As of June 1, 2022, 375 subjects were enrolled, 328 subjects completed 2 cycles of OCR, 289 subjects completed 3 cycles, 250 subjects completed 4 cycles, 218 subjects completed 5 cycles, 173 subjects completed 6 cycles, 130 patients completed 7 cycles, 102 subjects completed 8 cycles, 53 subjects completed 9 cycles, and 18 subjects completed 10 cycles. The population was 73% female, with an age range of 18-75. Sixty-five percent had RRMS and 35% PMS (PPMS and SPMS) with an EDSS range of 0-7.5;22% had a baseline EDSS of >= 6.0 (median 3.0). Twenty-two patients (6%) had serious non-COVID infections (requiring hospitalization) with no correlation to age or disability. Seven patients (2%) were hospitalized with COVID-19, 2 of whom died. Patients with an EDSS >= 6.0 had a slightly higher rate of UTIs as compared to the 5-year clinical trial data. There was no increase in HSV or zoster in older and/or more disabled patients. Malignancies occurred at a rate similar to that in the general MS population. Conclusion(s): With the exception of UTIs, which were more prevalent in patients with an EDSS > 6, we did not observe a higher rate of AEs in older and/or more disabled patients.

A partnership approach to supporting the health and wellbeing of the Charedi (Orthodox Jewish) community in London

BACKGROUND: There is a need for a specific programme of engagement around COVID-19 vaccination with the Charedi Orthodox Jewish community in Stamford Hill, London, UK. We co-produced a live event for women on COVID-19 safety and vaccination and wider health topics to support vaccine uptake and improve awareness of health and wellbeing issues. METHODS: For this qualitative analysis, we organised an event that was designed and delivered by a local community organisation in partnership with regional and local health partners and community groups. The event was for Charedi women aged 16 years and older, and provided information on COVID-19, childhood immunisations, oral health and dental hygiene, childhood respiratory infections, and mental health. The event included health stalls, a panel session, co-designed culturally competent physical information, and the opportunity to speak with health professionals. We evaluated the event using attendees' feedback forms, collected in person at the end of the event, and a thematic analysis of semi-structured interviews with organisers from community and statutory organisations. The evaluation was informed by a co-produced logic model and outcomes framework. FINDINGS: More than 100 women attended the event on March 28, 2022. Feedback suggested the focus on wider health issues was valued, and a greater number of more targeted events (eg on health for women older than 40) would be beneficial. Dental health, COVID-19 vaccination, and childhood immunisations were identified as the most important topics by participants. 16 (55%) of 29 respondents stated they would attend a similar event again, 12 (41%) stated they were unsure, and one (3%) said they would not attend again. Informal feedback from the community highlighted that the event was useful and acted as a basis for further engagement and collaboration with the community. INTERPRETATION: Our findings emphasised the need to work in partnership with a lead community organisation to identify and address principal health challenges within communities, to share community-specific insights, and to promote community events through community communication channels. Statutory institutions should engage with local community organisations to support and facilitate public health interventions to increase relevant vaccine uptake and to improve awareness around wider health and wellbeing issues and services. FUNDING: None.

Glossodynia, burning mouth syndrome, and COVID-19

PURPOSE: To evaluate whether the prevalence of glossodynia increased among patients affected by COVID-19 compared to other hospital populations. METHODS: The i2b2 patient registry platform at the University of Florida Health Center was used to generate a count of patients using the international classification of diseases (ICD)-10 diagnosis codes from October 2015 to June 2021. Logistic regression of the aggregates was used for analysis. RESULTS: Of the patients with both glossodynia and COVID-19, 60% were females, 32% were African American, 64% were white, and 100% were adults. There were 72% females, 19% African Americans, 72% whites, and 93% adults with glossodynia only. For COVID-19 patients, 57% were females, 23% were African American, 56% whites, and 90% were adults. The odds ratio (OR) for glossodynia in the COVID-19 patients was significant (OR = 2.9;95% CI, 1.94-4.32;P < 0.0001). CLINICAL SIGNIFICANCE: Glossodynia is significantly more common in COVID-19 patients and should be considered in the differential diagnoses among the oral complications of this infection.

Increased occurrence of temporomandibular joint disorders in COVID-19 confirmed patients

PURPOSE: To examine the prevalence of temporomandibular joint disorders (TMJD) in COVID-19 confirmed patients before and after adjustments for risk factors such as fibromyalgia, nocturnal bruxism, and anxiety disorders. METHODS: The i2b2 database was used to query searches of patient records at University of Florida Health Centers. Queries were submitted for the number of total hospital patients, TMJD cases, COVID-19 cases, and TMJD with COVID-19 cases from December 2019 to July 2021. Additional searches excluded fibromyalgia, nocturnal bruxism, and anxiety to examine their prevalence as risk factors. RESULTS: Out of the 548,646 total hospital patients, 86 had a diagnosis of both COVID-19 and TMJD, 14,836 had only COVID-19, and 1,856 had only TMJD. The odds ratio (OR) for having TMJD with COVID-19 was 1.7, with around 80% of TMJD occurring in young adult females. Excluding fibromyalgia and nocturnal bruxism did not change the OR. Anxiety was present in 37% of COVID-19 with TMJD cases and exclusion of this population significantly diminished the odds ratio to 1.08. These results demonstrate a correlation between COVID-19 and TMJD that dissolves when adjusting for stress. Thus, anxiety is a significant factor in the prevalence of TMJD in COVID-19 patients. CLINICAL SIGNIFICANCE: COVID-19 positive patients demonstrate an increased risk of developing TMJD, with a correlation to stress and anxiety that should be addressed during treatment.

Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab.

BACKGROUND: The COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab, an anti-CD20 therapy. Ocrelizumab has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. We sought to provide data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in ocrelizumab-treated patients, and to determine what variables correlate with vaccine immunogenicity. We hypothesized that patients without a humoral response to SARS-CoV-2 vaccination would still have intact T-cell responses. METHODS: We conducted a prospective, observational, single center cohort study of patients with MS treated with either ocrelizumab or natalizumab as a comparator between March 2, 2021, and July 1, 2021. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than ocrelizumab within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed prior to and 3-4 weeks post vaccination to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Data were analyzed using descriptive statistics, Fisher's exact test, and Wilcoxon rank sum. RESULTS: Forty-eight patients were enrolled in the study, 69% treated with ocrelizumab and 31% treated with natalizumab. Eighteen percent of ocrelizumab and 100% of natalizumab patients had a positive antibody response. In ocrelizumab-treated patients, there was no correlation between age, sex, BMI, total number of infusions, immunoglobulin G, CD19, or absolute lymphocyte count and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P = 0.062). All ocrelizumab patients with negative antibody responses had positive T-cell responses. CONCLUSIONS: Treatment with ocrelizumab substantially impaired the humoral response to SAR-CoV-2 vaccination but did not impair T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.

Increased odds ratio for erectile dysfunction in COVID-19 patients.

PURPOSE: Erectile dysfunction and COVID-19 share similar risk factors, including vascular disruption of integrity, cytokine release, cardiovascular disease, diabetes and obesity. The aim of this study was to investigate the association between erectile dysfunction and COVID-19 patients. METHODS: Odds ratio for erectile dysfunction in patients with a history of COVID-19 with and without comorbidities were calculated using a patients' registry platform i2b2. ICD-10 diagnoses codes were accessed for queries and data were analyzed using logistic regression. RESULTS: Patients with COVID-19 were 3.3 times more likely to have erectile dysfunction with 95% CI (2.8, 3.8). The association became stronger with odds ratio 4.8 (95% CI (4.1, 5.7)) after adjusting for age groups. The odds ratio remained the same after adjusting for smoking status with 3.5 (95% CI (3.0, 4.1)). After adjusting for race, COVID-19 patients were 2.6 (95% CI (2.2, 3.1)) times more likely to have erectile dysfunction. The odds ratio were 1.6, 1.8, 1.9 and 2.3 after adjusting for respiratory disease, obesity, circulatory disease and diabetes, respectively. CONCLUSION: COVID-19 and erectile dysfunction are strongly associated even after adjustment for known risk factors and demographics.

Humoral and T-cell responses to SARS-CoV-2 vaccination in multiple sclerosis patients treated with ocrelizumab

Background: The COVID-19 epidemic raises important questions about the efficacy of vaccines for people treated with ocrelizumab (OCR), an anti-CD20 therapy. OCR has been shown to reduce the humoral response to SARS-CoV-2 infection and vaccination, but the T-cell response to vaccination has not been fully characterized. Objectives: We measured antibodies in OCR-treated patients prior to and 3-4 weeks post SARS-CoV-2 vaccination. We measured T-cell responses in OCR-treated patients who made no antibodies. Aims: To provide additional data regarding B and T-cell mediated responses to SARS-CoV-2 vaccination in OCR-treated patients, and to determine which variables correlate with vaccine immunogenicity. Methods: We conducted a prospective, observational, single center cohort study of patients with MS treated with either OCR or natalizumab (TYS) as a comparator. Eligible patients were age 18 to 55 and had no known prior infection with, or vaccination against, SARS-CoV-2. Patients with prior use of immunosuppressive or chemotherapeutic agents, or treatment with any anti-CD20 therapy other than OCR within 12 months of enrollment, were excluded. The Roche Elecsys anti-SARS-CoV-2 S immunoassay was performed to evaluate the antibody response to SARS-CoV-2 spike IgG. The Adaptive Biotechnologies T-Detect COVID Test was performed to evaluate the adaptive T-cell immune response to SARS-CoV-2 in OCR-treated patients with no detectable antibodies. Results: Forty-eight patients were enrolled in the study, 69% treated with OCR and 31% treated with TYS. Eighteen percent of OCR and 100% of TYS patients had a positive antibody response. In OCR-treated patients, there was no correlation between age, sex, BMI, total number of infusions, IgG, CD19, or ALC and antibody response. There was a trend suggesting that a longer interval between the last infusion and vaccination increased the likelihood of producing antibodies (P=0.062). All OCR patients with negative antibody responses had positive adaptive T-cell responses. Conclusions: Treatment with OCR impaired the humoral response to SAR-CoV-2 vaccination, with only 18% of patients having a detectable antibody response. However, all patients without measurable antibodies had SARS-CoV-2 specific T-cell responses. Further research is needed to determine if the T-cell response to SARS-CoV-2 vaccination is sufficient to prevent infection or reduce severity of COVID in patients who did not produce antibodies.

Increased Prevalence of Dysgeusia in Pediatric Patients Diagnosed with COVID-19

Purpose: An altered sense of taste (dysgeusia) has been associated with COVID-19 infection in adults but is not sufficiently documented in children. The purpose of this study was to assess the odds ratio for dysgeusia associated with COVID-19 in a pediatric population of a major health center. Methods: Deidentified aggregate data, provided by the chief data officer (Informatics for Integrating Biology and the Bedside-I2B2) from June 2015 to October 2020, was used for correlation using the dysgeusia code (ICD 10 R43.2) with and without positivity for COVID-19. COVID-19 patients were measured from January 2020 to October 2020. Results: Among the 552 children who tested positive for COVID-19, nine also tested positive for dysgeusia and were older than nine years of age (odds ratio equals 149.5;95 percent confidence interval equals 66.9 to 334.3;P<0.001). Conclusions: Based on a strong association between COVID-19 and dysgeusia in children, dental professionals treating children are recommended to include questions about recent changes in appetite and taste as part of their patient screening COVID-19 questionnaire.

Prevalence and correlates of sexting and cybersex use among adults before and during COVID-19 social distancing measures in panama

Background Lockdown and other COVID-19 social distancing measures (COVID-19-measures) may influence virtual sexbehaviour due to increased screen time and decreased in-person sexual activity. This analysis describes the prevalence and factors associated with virtual sex before and during COVID- 19 measures in Panama. Methods An online survey conducted among ≥18 years individuals residing in Panama using social media recruitment, from August 8-September 12, 2020, at the end of strict lockdown measures. Questions included demographics, virtual sex (sexting [sharing/receiving nude/semi-nude photos/video] and cybersex [sexual acts in front of a camera] three months before and during COVID-19-measures. Logistic regression was used to identify associations with increased use of virtual sex. Results Overall, 960 individuals participated;526 (54.8%) identified as cis-women, 366 (31.1%) as cis-men, and 68 (7.1%) as non-binary/another gender;median age was 28y (IQR:23-37y). Before COVID-19-measures, 44.1% (369/837) reported sexting, 20.4% (172/842) cybersex, 46.4% (392/485) virtual sex. During COVID-19-measures, sexting, cybersex and virtual sex increased for 17.4%(139/797), 9.4%(74/790), and 19.9%(159/800) of participants, respectively. More cis-men reported virtual sex increase than cis-women (25.7% vs 17.2% [rural/urban adjusted]AOR=1.69, 95%CI:1.18-2.43). Bisexual (38.7% [gender and urban/rural adjusted]AOR=2.08, 95% CI:1.09-3.95) and lesbian/gay participants (42.4%,AOR=2.64, 95%CI:1.47-4.73) reported virtual sex increase more frequently compared to heterosexual participants (16.1%). Increase in casual sex was associated with increase in virtual sex (45.0% vs less casual sex 25.3%, AOR=4.06, 95% CI:1.24-13.35). Increased pornography use was associated with increased virtual sex (52.0% vs 7.8% decreased pornography, AOR=5.68, 95%CI:2.40-13.44). Among participants with a long-term partner, virtual sex increased among those who reported more partnership conflicts during than before COVID-19-measures (27.8% vs 12.8% among those who reported fewer conflicts, AOR=2.88, 95%CI:1.45-5.72). Conclusions Virtual sex was common before COVID-19-measures in Panama. During COVID-19-measures, virtual sex increased among cis-men, lesbian/gay and bisexual participants. Virtual sex was associated with increased pornography use, casual sex, and increased conflicts with long-term partners.

Transport and Fate of Virus-Laden Particles in a Supermarket: Recommendations for Risk Reduction of COVID-19 Spreading

The transport of virus-laden particles was investigated numerically in an archetypical supermarket configuration of area 1,200 m(2) and ceiling height of 4.5 m. The particles were tracked using a Lagrangian particle tracking code coupled with the computational fluid dynamics (CFD) model Ansys Fluent. Air transport was assumed to occur due to indoor ventilation. Flow dynamics were simulated using the Reynolds-averaged Navier Stokes (RANS) approach. The movement and spreading of 5- and 20-mu m particles were studied with 0%, 25%, and 100% attachment efficiencies on surfaces in the supermarket. We found that the indoor airflows can significantly enhance the transport of particles (e.g., >15 m for 5 mu m, and >5 m for 20 mu m);therefore, the 6-ft (2.0 m) social distance recommended by health experts would not be sufficient to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the attachment on surfaces reduces the transport of particles significantly within the supermarket, and that an attachment efficiency of 25% results in transport similar to that resulting from 100% efficiency. This suggests that the type of surfaces is not crucial in terms of air transport of particles. We support the existing approaches for reducing exposure between people through the adoption of one-way movement within an aisle. However, we also propose placing display shelves within the aisles in a staggered way to form baffles that would both increase the surface area and block the transport of airborne particles. We found that virus-laden particles could be sucked into the ventilation system through return vents, and could pose potential infection risks for the buildings connected to the same ventilation system. Hence, high-efficiency particulate air (HEPA) filters and pleated filters with a minimum efficiency reporting value (MERV) greater than 12 are recommended. (C) 2021 American Society of Civil Engineers.

COVID-19 Severity and Stroke: Correlation of Imaging and Laboratory Markers.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) appears to be an independent risk factor for stroke. We hypothesize that patients who develop stroke while hospitalized for severe COVID-19 will have higher inflammatory markers and distinct stroke imaging patterns compared with patients positive for COVID-19 with out-of-hospital stroke onset and milder or no COVID-19 symptoms. MATERIALS AND METHODS: This is a retrospective case series of patients positive for COVID-19 on polymerase chain reaction testing with imaging-confirmed stroke treated within a large health care network in New York City and Long Island between March 14 and April 26, 2020. Clinical and laboratory data collected retrospectively included complete blood counts and creatinine, alanine aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer levels. All CT and MR imaging studies were independently reviewed by 2 neuroradiologists who recorded stroke subtype and patterns of infarction and intracranial hemorrhage. RESULTS: Compared with patients with COVID-19 with outside-of-hospital stroke onset and milder or no COVID-19 symptoms (n = 45, 52.3%), patients with stroke already hospitalized for severe COVID-19 (n = 41, 47.7%) had significantly more frequent infarctions (95.1% versus 73.3%, P = .006), with multivascular distributions (56.4% versus 33.3%, P = .022) and associated hemorrhage (31.7% versus 4.4%, P = .001). Patients with stroke admitted with more severe COVID-19 had significantly higher C-reactive protein and ferritin levels, elevated D-dimer levels, and more frequent lymphopenia and renal and hepatic injury (all, P < .003). CONCLUSIONS: Patients with stroke hospitalized with severe COVID-19 are characterized by higher inflammatory, coagulopathy, and tissue-damage biomarkers, supporting proposed pathogenic mechanisms of hyperinflammation activating a prothrombotic state. Cautious balancing of thrombosis and the risk of hemorrhagic transformation is warranted when considering anticoagulation.