ABSTRACT
Introduction: The COVID-19 pandemic afects everyday life, hospital infrastructures and cancer care worldwide and in Germany. While current infection rates nationwide are decreasing, a continuous long-term infection rate is expected until vaccine development. First data from China suggested that cancer patients are particularly susceptible and at higher risk of a severe course of the disease. Despite more data being available now, many open questions remain regarding the course of COVID-19 in cancer patients and the impact of cancer treatment. To prospectively address these questions, we initiated a multicentric, observational trial including cancer patients with COVID-19 in the Hamburg metropolitan region and parts of Schleswig-Holstein. Method(s): Patients with diagnosis of cancer and COVID-19, who were treated in the University Cancer Center Hamburg (UCCH), its contracted partner network or at the University Cancer Centers Kiel and Lubeck are included into the trial, which was initiated in April 2020. Data are collected as available from routine clinical care and include demographic and biometric data, medical history, baseline infection data at inclusion as well as inpatient and intensive care unit admissions. Upon consent, patients provide peripheral blood samples for a prospective biobanking with the aim of investigating immune response, immunity and predictive outcome markers. Recruitment is planned for a one-year period. Result(s): As of June 30th 2020, 17 patients of which 13 were male were included afer signing informed consent. Median age was 64 years. 12 of the 17 patients had hematologic disease, mostly acute leukemia. Two patients had solid tumors and three patients had both hematologic and solid malignancy. In 71 % of included patients COVID-infection was diagnosed while being hospitalized due to their oncologic disease. Five patients required mechanical ventilation in the course of disease, one patient died due to the infection. Updated data will be presented at the meeting. Conclusion(s): The prospective registrational COVIDHELP trial will continuously include patients with malignant diseases and COVID-19 during the current pandemic. Our analysis will help to better understand the clinical course, potential impact of intrinsic and extrinsic factors as well as immune response to COVID-19 infection in cancer patients and thus facilitate clinical decision making concerning therapy discontinuation and identifcation of subgroups at specific risk.
ABSTRACT
Introduction: Up to now,reliable results regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with multiple myeloma (MM), especially under current myeloma-directed therapy, are scarcely available. Here, we report an analysis describing the level of post-vaccination antibody titers after the 1 stand 2 ndanti-SARS-CoV-2 vaccination depending on therapy, remission status, and B- and T-cell numbers in patients with MM and related plasma cell neoplasia. Methods: This observational single-center study included patients aged ≥18 years with diagnoses of MM, monoclonal gammopathies of clinical significance (MGCS), or systemic light-chain amyloidosis (AL) who were eligible for Anti-SARS-CoV-2 vaccination according to the International Myeloma Society recommendations. Patients with prior COVID-19 infections were excluded. Samples were analyzed for the presence of SARS-CoV-2 specific antibodies using the quantitative anti-spike IgG (SARS-CoV-2 spike RBD IgG, cut off ≥ 0.8 BAU/ml) according to manufacturer's recommendations. SARS-CoV-2 spike protein antibody titer (SP-AbT) were evaluated after at least 7 days after the 1 stand 2 ndvaccination, respectively. This study was performed between January 1 - July 15, 2021, at the University Medical Center Hamburg-Eppendorf, Germany, as part of the COVIDOUT trial (NCT04779346). All patients provided written informed consent. Aims of this study were to evaluate a possible correlation between SP-AbT and CD19+ B lymphocyte count, as well as to identify other factors impacting vaccination response. Results: 82 patients who received SARS-CoV-2 vaccines (including 67 patients with mRNA-, 8 with vector-based vaccines and 4 heterologous vaccinations) were included. 74 patients had diagnosis of MM, 4 of MGCS/smoldering MM and 4 of AL. Median age was 68 years (range 35-85) and 49 patients were male. In total, 37 patients (45.1%) received anti-CD38- and 2 (2.4%) anti-SLAMF7-targeting therapies at the time of vaccination, 52 (63.4%) patients received immunomodulatory drug (IMID)-based treatments and 13 patients (15.9%) were under active surveillance. 59% of patients had newly diagnosed and 41% refractory or relapsed disease. In total, 75.6% of all patients were in deep remissions (very good partial remission or better). Assessment of anti-SARS-CoV-2 antibody titers took place in median 23 days (range [r] 8-63 days) after the 1 stand 21 days (r: 6-53) after the 2 ndvaccination. A positive SARS-CoV-2 SP-AbT was detected in 31.9% of assessable patients with an overall median SP-AbT of 0 BAU/ml (r: 0-10328, mean 202.36) after the 1 stvaccination and increased up to 88.9% (median SP-AbT of 216.87 BAU/ml, r: 0-25720, mean 2139.29) after 2 ndvaccination. Of the patients not showing positive SP-AbT after the 1 stvaccination, 80.9% became positive after 2 ndvaccination, while 19.1 % remained negative. Median SP-AbT titer was significantly lower compared to patients who became positive already after 1 stvaccination (51.04 vs. 2191.87 BAU/ml, p<0.0001). Regarding immune status, a CD19+ B cell count of median 33.5/µl (r: 1-696/µl) was seen in the overall patient cohort;in patients with negative SP-AbT, median CD19+ B cell numbers were significantly lower compared to patients with positive titers (median CD19+ B cells: 2.0 vs. 52.5/µl, p=0.005). Overall, CD19+ B lymphocyte numbers correlate significantly with positive SP-AbT results and were identified as predictive factor in multivariate analysis. The previously suggested threshold of 30 CD19+ B cells/µl as being predictive for SP-AbT development could be validated. SP-AbT concentration was significantly lower with older age. Furthermore, median SP-AbT were significantly lower in patients with current anti-CD38 directed therapy (median SP-AbT: 1085.4 vs. 62.05 BAU/ml, p < 0.005). Conclusions: In spite of immunodeficiency and immunosuppressive therapy, most MM patients develop SP-AbT. However, about 11% of MM patients failed to develop SP-AbT after full vaccination, and thus remain on risk for COVID-19. Higher counts of CD19+ B lymphocytes, ith a threshold of 30 CD19+ B lymphocytes/µl, are predictive for SP-AbT formation and may further help to identify patients at higher risk of insufficient vaccination response in whom control of vaccination success and potential third vaccination are particularly important. Disclosures: Bokemeyer: GlaxoSmithKline: Research Funding;Inside: Research Funding;IO Biotech: Research Funding;Eisai: Research Funding;Daiichi Sankyo: Research Funding;Gilead Sciences: Research Funding;Blueprint Medicine: Research Funding;BerGenBio: Research Funding;Janssen-Cilag: Research Funding;Isofol Medical: Research Funding;AOK Health insurance: Consultancy;GSO: Consultancy;Bayer Schering Pharma: Consultancy;Gylcotope GmbH: Research Funding;ADC Therapeutics: Research Funding;Apellis Pharmaceuticals: Research Funding;Amgen: Research Funding;Alexion Pharmaceuticals: Research Funding;Agile Therapeutics: Research Funding;Merck Serono: Consultancy, Other: Travel accomodation;Lilly/ImClone: Consultancy;Merck Sharp Dohme: Consultancy, Honoraria;AstraZeneca: Honoraria, Research Funding;BMS: Honoraria, Other: Travel accomodation, Research Funding;Bayer: Honoraria, Research Funding;Roche: Honoraria, Research Funding;Sanofi: Consultancy, Honoraria, Other: Travel accomodation;Merck KGaA: Honoraria;Abbvie: Research Funding;Boehringer Ingelheim: Research Funding;Celgene: Research Funding;Astellas: Research Funding;Karyopharm Therapeutics: Research Funding;Lilly: Research Funding;Millenium: Research Funding;MSD: Research Funding;Nektar: Research Funding;Rafael Pharmaceuticals: Research Funding;Springworks Therapeutics: Research Funding;Taiho Pharmaceutical: Research Funding;Pfizer: Other. Sinn: Incyte: Honoraria, Research Funding;Pfizer: Honoraria;Servier: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Research Funding;Astra Zenica: Consultancy, Research Funding;MSD: Consultancy, Research Funding;Sanofi: Consultancy;Bayer: Research Funding;BMS: Honoraria, Research Funding. Leypoldt: GSK: Consultancy, Other: Meeting attendance;Sanofi: Consultancy;Abbvie: Other: Meeting attendance. Weisel: Adaptiv Biotec: Consultancy;Abbvie: Consultancy;BMS: Consultancy, Honoraria, Research Funding;Celgene: Consultancy, Honoraria, Research Funding;Amgen: Consultancy, Honoraria, Research Funding;GSK: Consultancy, Honoraria;Janssen: Consultancy, Honoraria, Research Funding;Karyopharm: Honoraria;Novartis: Honoraria;Oncopeptides: Consultancy, Honoraria;Pfizer: Honoraria;Roche: Honoraria;Takeda: Honoraria;Sanofi: Consultancy, Honoraria, Research Funding.