ABSTRACT
Purpose: The aim of this study was to evaluate the clinical features and course of coronavirus disease 2019 (COVID-19) in individuals with rheumatic disease.Materials and Methods: This retrospective study was carried out at the Erciyes University rheumatology outpatient clinic from July 1 to August 1, 2021. The demographic and clinical data and summarized COVID-19 history, clinical course of COVID-19, fatigue, and pain levels of patients with rheumatic disease were obtained from our institutional electronic registration database and patient files. Results: Recruited participants were 106 individuals (83% female, %17 male) with rheumatic disease who had been confirmed by laboratory tests to have COVID-19 and recovered from the COVID-19 infection. Their mean age and body mass index (BMI) were 48.69 +/- 11.5 years and 29.89 +/- 6.76 kg/m2, respectively. Additionally, 21 (19.8%) had been hospitalized, and five (4.7%) had been admitted to the intensive care unit. The most common rheumatic diseases were axial spondyloarthritis (40;37.7%) and rheumatoid arthritis (26 cases;24.5%). Patients who received conventional synthetic disease-modifying drugs (csDMARDs) reportedly experienced more pain, fatigue, and headaches than those in the biologic agent and non -steroidal anti-inflammatory drug (NSAID) groups.Conclusion: Our study results reveal similar symptoms and hospitalization rates among patients with rheumatic disease who recovered from COVID-19 and received either csDMARDs, biologic agents, or NSAIDs. However, patients in the csDMARD group reported more pain, fatigue, and headache compared to the other groups.
ABSTRACT
Introduction: World Marrow Donor Association (WMDA) promotes global collaboration for the benefit of stem cell donors and transplant patients. WMDA activities include recording the number of unrelated hematopoietic stem cell (HSC) donations globally. Because the COVID-19 pandemic also has an impact on the treatment of patients with other diseases, we hypothesise that it also impacted the practice of unrelated hematopoietic stem cell transplantation (HSCT). We used the 2020 WMDA data to examine the trends in unrelated HSC donations during the COVID-19 pandemic globally, per continent and per country/region. Methods: Donor registries (DRs) and cord blood banks (CBBs) from 61 countries participated in the 2020 survey, compared to 59 countries in the 2019. Slight differences in participation between the data sets of 2019 and 2020 do not explain the trends we observe in HSC donations. Country/region-specific COVID-19 data on cases and deaths were obtained from the data repository operated by the Johns Hopkins University Center for Systems Science and Engineering(https://github.com/CSSEGISandData/COVID-19, accessed July 12, 2021);and population data were retrieved from the Worldometer website(https://www.worldometers.info/, accessed July 12, 2021). Results: HSC donations from unrelated donors (peripheral blood stem cells (PBSC) and bone marrow (BM)) decreased from 20,330 in 2019 to 19,623 in 2020 (-3.5%), compared to an average annual growth rate of 3.9% from 2015 to 2019 (figure 1). The 3.5% decrease is composed of a 29.0% decrease for BM and a 2.6% increase for PBSC, resulting in a drop in the BM share of unrelated HSC donations from 19.3% in 2019 to 14.2% in 2020. The number of cord blood unit (CBU) shipments globally decreased with 3.5% from 2,851 to 2,750. The percentage of national use of HSC products (PBSC and BM) increased from 51.2% to 53.5%. When considering the continent on which the patient is transplanted (table 1), the change rate of use of HSC donated products in 2020 vs. 2019 ranged from -28.0% in South America to +18.2% in Africa. In absolute numbers, the largest decrease of HSC donations occurred for patients in Asia (n=-485) followed by Europe (n=-205), and the largest increase occurred in North America (n=+88) followed by Oceania (n=+25). The share of HSC donations requiring intercontinental transport decreased from 24.6% in 2019 to 21.9% in 2020. In terms of the country/region of transplant (table 2), the largest percentage decrease occurred in Colombia (-90,5%) followed by Russia (-55,5%). In absolute numbers, the largest decrease occurred in Turkey (-147), with Japan following (-128, although Japan saw an increase of CBU use of +106). The highest growth rate was observed in Iran (+28,7%), followed by South Africa (+28,2%). In absolute figures, the greatest increase occurred in Italy (+67). The two countries receiving the largest HSC donation numbers showed no major changes versus the previous year: USA: +0.6% (although a decrease for CBU of -21,0% was observed) and Germany: -2.4%. We did not find any significant correlation between the numbers of COVID-19 cases or COVID-19-related deaths per 1 million inhabitants with the HSC donation numbers (Spearman's r=0.05 for cases and =0.08 for deaths). Discussion: The decline in the number of unrelated HSC donations in 2020 suggests an impact of the COVID-19 pandemic on HSC donation and unrelated HSCT. The significant decrease in BM collections and intercontinental/cross-border shipments can be explained by logistically complex processes, as well the increased risk to the donor of being exposed to an operative procedure. CBU as a stem cell source potentially circumvents these logistical complications. However, on a global scale our data does not show increased use of CBU suggesting that decisions to use CBU as a stem cell source did not change in the pandemic. We were unable to demonstrate a correlation between country/region-specific severity of the pandemic and HSC donation numbers. We suspect this is due to the data quality of reported number of COVID-1 cases and COVID-19-related deaths. Also, we did not gather monthly data and therefore could not specify pandemic waves. In conclusion, we would like to point out the fact that global exchanges of HSC products continued and only decreased slightly is an extraordinary achievement of DRs, CBBs and their donors and is a testament to the importance of international collaborations in the WMDA. [Formula presented] Disclosures: Devine: Orca Bio: Consultancy, Research Funding;Johnsonand Johnson: Consultancy, Research Funding;Sanofi: Consultancy, Research Funding;Magenta Therapeutics: Current Employment, Research Funding;Tmunity: Current Employment, Research Funding;Vor Bio: Research Funding;Kiadis: Consultancy, Research Funding;Be the Match: Current Employment. Shaw: Orca bio: Consultancy;mallinkrodt: Other: payments. Forman: Mustang Bio: Consultancy, Current holder of individual stocks in a privately-held company;Lixte Biotechnology: Consultancy, Current holder of individual stocks in a privately-held company;Allogene: Consultancy.
ABSTRACT
Introduction: Extramedullary disease (EMD) in patients (pts) with multiple myeloma (MM) is a poor prognostic feature which is not curable with currently approved treatments. Consequently, there is a significant unmet need for effective therapies with good safety profiles. Daratumumab with cyclophosphamide, bortezomib and dexamethasone (daraVCD) is a novel treatment combination with a good efficacy profile in pts with EMD based on preclinical synergistic data. Methods: EMN19 is a phase 2, open-label, multicenter study which aims to enroll 40 MM pts presenting with EMD either at diagnosis or following one line of treatment but not refractory to bortezomib-based regimens, from 8 sites in Turkey, Greece and Italy. Pts with bortezomib or daratumumab hypersensitivity, who received previous autologous stem cell transplant (ASCT) ≤12 weeks before Day 1 of treatment Cycle 1, or with previous allogenic stem cell transplant were excluded. Daratumumab was initially administered intravenously at 16 mg/mL, and since July 2020 has been administered subcutaneously at a fixed dose of 1800 mg, weekly during Cycles 1-2, every 2 weeks for Cycles 3-6, and every 4 weeks thereafter. Intravenous bortezomib 1.5 mg/m 2 and oral/intravenous cyclophosphamide 300 mg/m 2 is administered weekly, and oral/intravenous dexamethasone 20 mg is administered on Days 1, 2, 8, 9, 15, 16, 22 and 23. DaraVCD will be administered until progression or unacceptable toxicity unless refractory disease is detected by the end of Cycle 3 (progressive disease [PD] or failure to achieve a confirmed partial response [PR] or better). The present analysis includes pts who initiated study treatment ≥3 months prior to the cut-off date (01 June 2021). Results: In total, 34 patients were screened, 27 patients were enrolled, 2 relapsing patients died during the screening phase due to severe COVID-19 infection, 22 pts were analyzed (59% female;median age 56 years, range 44-77);14 pts (64%) were still on treatment and 8 (36%) discontinued;due to inadequate response after 3 cycles of treatment (n=3, 38%), PD (n=4, 50%), death (n=1, 13%). Fourteen pts (64%) were newly diagnosed and 8 (36%) first relapsed. International Staging System stage at baseline was I, II and III for 8 (36%), 9 (41%) and 5 (23%) pts, respectively. Eastern Cooperative Oncology Group performance status was 0, 1 and 2 for 14 (64%), 7 (32%), and 1 patient (5%), respectively. On average, 3.0 (range 1-20) extramedullary plasmacytomas were observed per patient;most commonly reported sites were thorax (6 pts, 27%), brain, head and lower extremities (4 pts, 18% each). Twenty (91%) pts had ≥1 serious or non-serious treatment-emergent adverse event (TEAE);8 pts (36.4%) experienced ≥1 sTEAEs;COVID-19 infection (n=3, 14%) urinary tract infection (n=2, 9%), infectious myocarditis, hip arthroplasty, pneumonia, cytomegaloviral pneumonia and thrombocytopenia (n=1 each, 4.5%). Thirteen (59%) pts ≥1 Grade 3/4 TEAE;neutropenia observed in 8 pts (36%), followed by thrombocytopenia (n=4, 18%) and COVID-19 infection (n=3, 14%). Overall, 16 (73%) pts missed ≥1 dose of any of the study drugs;2 (9%) pts missed ≥1 dose due to COVID-19 infection (7 doses), 8 (36%) due to COVID-19 vaccination (37 doses), 2 (9%) due to other COVID-19-related issues (65 doses), 10 (46%) due to other safety events (104 doses) and 9 (41%) due to other reasons (25 doses). Overall, 20 cycle delays were observed in 13 (59%) pts, with median (range) delay of 12.0 (4-133) days. Two pts (9%) had a cycle delay due to COVID-19 infection (2 cycles), 1 (5%) due to COVID-19 vaccination (1 cycle), 5 (23%) due to adverse events (8 cycles), 2 (9%) due to ASCT (2 cycles) and 7 (32%) due to other reasons (7 cycles). Total number of missed doses (missed doses due to COVID-19-related issues) were 17 (3) for daratumumab, 53 (11) for bortezomib, 45 (9) for cyclophosphamide and 123 (86) for dexamethasone;238 doses missed in total. No fatalities occurred due to any infection. Conclusions: DaraVCD was associated with a good safety profile in this high ri k MM with EMD patient population. The COVID-19 impact on missed doses was greater for dexamethasone (>60% of missed doses) than other components (~20%), however overall, the pandemic did not significantly affect the patients' safety and data integrity of the study. The enrollment in the study is ongoing, and more safety and efficacy data will become available with the inclusion of additional pts in an updated analysis. Disclosures: Beksac: Amgen,Celgene,Janssen,Takeda,Oncopeptides,Sanofi: Consultancy, Speakers Bureau. Tuglular: GSK: Honoraria, Research Funding;Amgen: Honoraria, Research Funding;Karyopharm: Honoraria, Research Funding;Abbvie: Honoraria, Research Funding;Janssen-Cilag: Honoraria, Research Funding;Genesis Pharma: Honoraria, Research Funding;Sanofi: Honoraria, Research Funding. Cavo: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Accommodations, Speakers Bureau;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;GlaxoSmithKline: Consultancy, Honoraria;AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squib: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Adaptive Biotechnologies: Consultancy, Honoraria. Gay: GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees;Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees;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;Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Oncopeptides: Membership on an entity's Board of Directors or advisory committees;Bluebird bio: Membership on an entity's Board of Directors or advisory committees. Katodritou: GSK, Amgen, Karyopharm, Abbvie, Janssen-Cilag, Genesis Pharma, Sanofi: Honoraria, Research Funding. Merante: EMN Italy Medical Monitor: Research Funding. Manousou: Health Data Specialists: Current Employment. Sonneveld: Karyopharm: Consultancy, Honoraria, Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Celgene/BMS: Consultancy, Honoraria, Research Funding;SkylineDx: Honoraria, Research Funding;Takeda: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding. Terpos: GSK: Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Genesis: Consultancy, Honoraria, Research Funding;Novartis: Honoraria;Janssen-Cilag: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;BMS: Honoraria;Takeda: Consultancy, Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Research Funding.