Project description:Few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with hematological malignancies, and particular, plasma cell neoplasia. This ongoing single-center study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma and related plasma cell dyscrasia, after the first dose of anti-SARS-CoV-2 vaccination. The 82 patients included in this study received SARS-CoV-2 vaccines (including mRNA- and vector-based vaccines) as a routine measure. After the first vaccination, a positive SARS-CoV-2 spike protein antibody titer (SP-AbT) was detected in 23% of assessable patients. SARS-CoV-2 SP-AbT was significantly higher in patients with higher CD19+ B lymphocyte counts. A cut-off value of ≥30 CD19+ B cells/µL was significantly positive correlating with higher SARS-CoV-2 SP-AbT. In contrast, current treatment with anti-CD38-antibodies has led to significantly reduced SP-AbT titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease significantly correlated negatively with SARS-CoV-2 SP-AbT. Conversely, treatment with immunomodulatory drugs did not harm the development of antibody titers. Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination and need booster vaccination.
Project description:Background Up to now, only few data are available regarding the efficacy of anti-SARS-CoV-2 vaccines in patients with plasma cell neoplasia. This ongoing observational study aimed to describe the level of post-vaccination anti-SARS-CoV-2-antibodies depending on B lymphocyte count, current therapy, and remission status of patients with multiple myeloma (MM) and related plasma cell dyscrasias, after the first dose of anti-SARS-CoV-2 vaccination. Methods In this single-center study, patients aged 18 years and older with a confirmed diagnosis 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 were included. Data were collected between January 1st and May 21th, 2021, at the department of oncology and hematology at the University Medical Center Hamburg-Eppendorf, Germany. The primary aim of this study was to evaluate a possible correlation between antibody titers and CD19+ B lymphocyte count and secondary to identify other possible factors influencing immune response. This study is part of the COVIDOUT trial (NCT04779346). Written informed consent was provided by each patient according to local requirements. Results A total of 82 patients were included in this study. The median age was 67.5 years (range 40-85 years). 78 patients had MM, 2 MGCS, and 2 AL. Overall, 63 patients were vaccinated with mRNA-based and 19 with vector-based vaccines, respectively. At the time of vaccination, 69 (84.1%) patients were under current anti-myeloma treatment. In total, 34 (41%) patients received anti-CD38-targeting therapies and 52 (63%) patients received IMiD-based therapies. 57 (69.5%) patients were in deep remissions (very good partial remission or better) at the time of vaccination. Assessment of anti-SARS-CoV-2 spike protein antibody titer (SP-AbT) took place on a median of 25 days after the first vaccination (SD ± 11.8). A positive SP-AbT was detected in 23% (17/74) of assessable patients. A cut-off value of ≥ 30 CD19+ B cells/µl was significantly positively correlating with higher SARS-CoV-2 SP-AbT. Individuals with current anti-CD38-antibody treatment showed lower SP-AbT and the likelihood for positive titer results was significantly lower in patients with current anti-CD38 treatment compared to those without. Treatment with immunomodulatory drugs did not harm the development of antibody titers. Furthermore, in multivariable linear regression, higher age and insufficiently controlled disease (≤ partial remission) were significantly negatively correlated with SARS-CoV-2 SP-AbT. Conclusion Based on our results, the majority of myeloma patients respond poorly after receiving the first dose of any anti-SARS-CoV-2 vaccination. Since both low CD19+ B lymphocyte count and CD38-directed therapy negatively impact vaccination response, booster vaccination seems therefore of utter importance.
Project description:Even though several SARS-CoV-2 vaccines have shown high effectiveness in the prevention of COVID-19 in healthy subjects, vaccination response in patients with plasma-cell-related disorders (PCD) remains widely unknown. Here, we report on an analysis describing the serological response after prime-boost SARS-CoV-2 vaccination in PCD patients, as compared to a healthy control group, and on possible influencing factors of serological responses. Blood samples were analyzed for the presence of quantitative anti-SARS-CoV-2 spike RBD Ig. A total of 82 patients were included; 67 received mRNA-, eight vector-based and four heterologous vaccinations. SARS-CoV-2 antibody titers (SP-AbT) were assessed in a mean of 23 days (SD ± 11 days) after the first and in a mean 21 days (SD ± 9) after prime-boost vaccination. A positive SP-AbT was detected in 31.9% of PCD patients after the first vaccination, and in 88.9% (44/49) after prime-boost vaccination, which was significantly less likely than that in the control group (100%, 78/78) (p = 0.008). Furthermore, we have been able to validate our previously suggested threshold of 30 CD19+ B lymphocytes/µL as being predictive for SP-AbT development. Despite anti-CD38 directed therapy, quadruplet treatment, higher age and missing deep remission, which correlated negatively with SP-AbT appearance, SP-AbT formation is possible in a majority of myeloma patients after prime-boost vaccination.
Project description:Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti-RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short- and long-term follow-up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short-term and 71% in long-term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS-CoV-2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS-CoV-2 might be induced by vaccination but do not correlate positively with serological responses.
Project description:BackgroundPatients with multiple myeloma (MM) were excluded from the original SARS-CoV-2 mRNA vaccine trials, which may influence vaccine hesitancy in this population. We prospectively characterized the safety and immunogenicity of two-dose SARS-CoV-2 mRNA vaccination in 44 patients with MM, who underwent vaccination from 12/17/2020 to 3/18/2021.ResultsRates adverse reactions were low and consistent with those documented in vaccine trials. Among those on MM therapy, 93% developed detectable anti-receptor binding domain (RBD) antibodies after dose 2, while 94% of patients not on MM therapy seroconverted.ConclusionsTwo-dose SARS-CoV-2 mRNA vaccination is mildly reactogenic and leads to high rates of seroconversion in patients with MM. These findings can provide reassurance to MM patients who are hesitant to receive SARS-CoV-2 mRNA vaccines.
Project description:BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20).ObjectivesHere, we investigated humoral and cellular immune responses, including anti-spike titers, neutralization against SARS-CoV-2 wild-type (WT), delta, and omicron variant and T cell responses of aCD20-treated relapsing-remitting MS patients following SARS-CoV-2 vaccination compared with healthy controls.MethodsBlood samples were collected within 4-8 weeks following the second vaccination against SARS-CoV-2. Sera were analyzed for anti-SARS-CoV-2 spike antibodies and neutralization capacity against pseudovirus for wild-type (WT), delta, and omicron variant. Peripheral blood mononuclear cells (PBMCs) were stimulated with a SARS-CoV-2 peptide pool and analyzed via flow cytometry.ResultsThe aCD20-treated MS patients had lower anti-SARS-CoV-2-spike titers, which correlated with B cell repopulation. Sera of aCD20-treated patients had reduced capacity to neutralize WT, delta, and omicron pseudoviruses in vitro. On the contrary, PBMCs of aCD20-treated patients elicited higher frequencies of CD3+ T cells and CD4+ T cells and comparable response of cytotoxic T cells, while Th1 response was reduced following restimulation with SARS-CoV-2.ConclusionIn summary, aCD20-treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with preserved cellular immune response, suggesting partial cellular protection against SARS-CoV-2.
Project description:BackgroundStreptococcus pneumoniae infection causes morbidity and mortality in multiple myeloma patients. Pneumococcal vaccination is commonly given to immunocompromised myeloma patients; however response data are sparse. Here, we present longitudinal response data to pneumococcal vaccination in multiple myeloma patients.MethodTwenty-eight multiple myeloma patients were included, 25 of whom were newly diagnosed. All the patients received two vaccines Prevnar13® and Pneumo23®. Serotype-specific IgG was measured by ELISA for all 23 vaccine serotypes at baseline, and then sequentially at different time points postvaccination until treatment ended. Response to vaccination is available for 20 patients. The primary endpoint was the incidence rate of patients who obtained an isotype response serum concentration after vaccination. Secondary endpoints included detailed isotype increase, time to first increase, further assessment of a decreased anti-pneumococcal serum concentrations following treatment including autologous stem cell transplantation (ASCT), rate of infection with a special attention to pneumococcal infection.ResultsThe median age was 66 years and the male to female ratio was 0.6. Anti-pneumococcal capsular polysaccharide (anti-PCP23) IgG, IgG2, IgA, and IgM responses were detected within 1 week postvaccination. Response to at least one subtype of antibody was obtained in 85% (n = 17) of patients, for at least two subtypes in 65% (n = 13), for at least three subtypes in 55% (n = 11), and 2 patients responded to all four subtypes. The median increase in the concentration of anti-PCP23 isotypes was threefold following vaccination, with the highest increase observed when Pneumo23® was given more than 30 days after Prevnar13®. The anti-pneumococcal geometric mean concentration decreased significantly for all subtypes over time independently of treatment approaches.ConclusionMyeloma has the ability to demonstrate a response to pneumococcal vaccine, independently of preexisting hypogammaglobulinemia and possibly of treatment-induced immunodepression. We also observed a drop in the serum response overtime and following autologous transplantation. Further studies in larger sample are needed to understand the benefit of vaccination strategies in these patients.