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1.
Front Immunol ; 13: 889138, 2022.
Article in English | MEDLINE | ID: covidwho-1875415

ABSTRACT

Background: Individuals with secondary immunodeficiencies belong to the most vulnerable groups to succumb to COVID-19 and thus are prioritized for SARS-CoV-2 vaccination. However, knowledge about the persistence and anamnestic responses following SARS-CoV-2-mRNA vaccinations is limited in these patients. Methods: In a prospective, open-label, phase four trial we analyzed S1-specific IgG, neutralizing antibodies and cytokine responses in previously non-infected patients with cancer or autoimmune disease during primary mRNA vaccination and up to one month after booster. Results: 263 patients with solid tumors (SOT, n=63), multiple myeloma (MM, n=70), inflammatory bowel diseases (IBD, n=130) and 66 controls were analyzed. One month after the two-dose primary vaccination the highest non-responder rate was associated with lower CD19+ B-cell counts and was found in MM patients (17%). S1-specific IgG levels correlated with IL-2 and IFN-γ responses in controls and IBD patients, but not in cancer patients. Six months after the second dose, 18% of patients with MM, 10% with SOT and 4% with IBD became seronegative; no one from the control group became negative. However, in IBD patients treated with TNF-α inhibitors, antibody levels declined more rapidly than in controls. Overall, vaccination with mRNA-1273 led to higher antibody levels than with BNT162b2. Importantly, booster vaccination increased antibody levels >8-fold in seroresponders and induced anamnestic responses even in those with undetectable pre-booster antibody levels. Nevertheless, in IBD patients with TNF-α inhibitors even after booster vaccination, antibody levels were lower than in untreated IBD patients and controls. Conclusion: Immunomonitoring of vaccine-specific antibody and cellular responses seems advisable to identify vaccination failures and consequently establishing personalized vaccination schedules, including shorter booster intervals, and helps to improve vaccine effectiveness in all patients with secondary immunodeficiencies. Trial registration: EudraCT Number: 2021-000291-11.


Subject(s)
COVID-19 , Inflammatory Bowel Diseases , Multiple Myeloma , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunization, Secondary , Immunocompromised Host , Immunoglobulin G , Immunologic Memory , Multiple Myeloma/therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Tumor Necrosis Factor-alpha , Vaccination
5.
Int J Hematol ; 115(5): 737-747, 2022 May.
Article in English | MEDLINE | ID: covidwho-1700452

ABSTRACT

We conducted a prospective, three-center, observational study in Japan to evaluate the prevalence of seropositivity and clinically protective titer after coronavirus disease 2019 vaccination in patients with plasma cell dyscrasia(PCD). Two-hundred sixty-nine patients with PCD [206 symptomatic multiple myeloma (MM)] were evaluated. Seropositivity was observed in 88.7% and a clinically protective titer in 38.3% of MM patients, both of which were significantly lower than those of healthy controls. Patients receiving anti-CD38 antibodies had much lower antibody titers, but antibody titers recovered in those who underwent a wash-out period before vaccine administration. Older age (≥65), anti-CD38 antibody administration, immunomodulatory drugs use, lymphopenia (<1000/µL), and lower polyclonal IgG (<550 mg/dL) had a negative impact for the sufficient antibody production according to multivariate analysis. Patients with clinically protective titer had a significantly higher number of CD19+ lymphocytes than those with lower antibody responses (114 vs. 35/µL, p = 0.016). Our results suggested that patients with PCD should be vaccinated, and that the ideal protocol is to temporarily interrupt anti-CD38 antibody therapy for a "wash-out" period of a few months, followed by a (booster) vaccine after the B-cells have recovery.


Subject(s)
COVID-19 , Multiple Myeloma , Vaccines , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Multiple Myeloma/therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2
6.
Br J Haematol ; 197(3): 293-301, 2022 05.
Article in English | MEDLINE | ID: covidwho-1642616

ABSTRACT

Myeloma patients frequently respond poorly to bacterial and viral vaccination. A few studies have reported poor humoral immune responses in myeloma patients to COVID-19 vaccination. Using a prospective study of myeloma patients in the UK Rudy study cohort, we assessed humoral and interferon gamma release assay (IGRA) cellular immune responses to COVID-19 vaccination post second COVID-19 vaccine administration. We report data from 214 adults with myeloma (n = 204) or smouldering myeloma (n = 10) who provided blood samples at least three weeks after second vaccine dose. Positive Anti-spike antibody levels (> 50 iu/ml) were detected in 189/203 (92.7%), positive IGRA responses were seen in 97/158 (61.4%) myeloma patients. Only 10/158 (6.3%) patients were identified to have both a negative IGRA and negative anti-spike protein antibody response. In all, 95/158 (60.1%) patients produced positive results for both anti-spike protein serology and IGRA. After adjusting for disease severity and myeloma therapy, poor humoral immune response was predicted by male gender. Predictors of poor IGRA included anti-CD38/anti-BCMA (B-cell maturation antigen) therapy and Pfizer-BioNTech vaccination. Further work is required to understand the clinical significance of divergent cellular response to vaccination.


Subject(s)
COVID-19 , Multiple Myeloma , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunity, Humoral , Male , Multiple Myeloma/therapy , Prospective Studies , SARS-CoV-2 , T-Lymphocytes , Vaccination
8.
JCO Clin Cancer Inform ; 5: 1096-1105, 2021 10.
Article in English | MEDLINE | ID: covidwho-1502035

ABSTRACT

Multiple myeloma (MM) is associated with the highest symptom burden and lowest health-related quality of life (HRQoL) among patients with hematologic malignancies. HRQoL in MM is heterogeneous, varying over the course of disease, with the highest burden at diagnosis and relapse. Patients with MM are increasingly being treated with oral maintenance medications at home. As a result, longitudinal monitoring of medication adherence and patient-reported outcomes, including HRQoL, could inform on disease status, therapeutic tolerability, and satisfaction with care. Digital health technologies, including telemedicine, mobile health, and wearable devices, are poised to become an integral part of modern health care, in part due to the surge in telemedicine necessitated by the COVID-19 pandemic. Although the literature has many reports on the use of digital health technologies in other types of cancers, fewer studies report on their application to MM. In the current narrative review, we survey the applications of digital health for MM. Although there is evidence that some are associated with improved health outcomes, challenges exist that must be met to ensure more widespread adoption. These include the need for increased awareness by patients and health care providers, lack of access by the typical older patient with MM, absence of randomized clinical trials, and low integration with current workflows such as electronic health records. Following our summary of technologies that could benefit patients with MM, we end by describing our vision for how they can be integrated into each phase of the patient journey.


Subject(s)
COVID-19 , Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Multiple Myeloma/therapy , Neoplasm Recurrence, Local , Pandemics , Quality of Life , SARS-CoV-2
10.
Blood Cancer Discov ; 1(3): 218-220, 2020 11.
Article in English | MEDLINE | ID: covidwho-1476893

ABSTRACT

Patients with active myeloma, especially with earlier stages of the disease, are susceptible to COVID-19 infection and can have adverse outcomes, even in those on first-line treatment. Importantly, myeloma therapy can be safely administered, and optimal control of myeloma is associated with improved outcome. See related video: https://vimeo.com/486246183/559a80cfae See related article by Hultcrantz et al., p. 234.


Subject(s)
COVID-19 , Multiple Myeloma , Humans , Multiple Myeloma/therapy , Pandemics , SARS-CoV-2
12.
Int J Hematol ; 115(1): 61-68, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1432631

ABSTRACT

BACKGROUND: "Hospital-at-home" (HAH) programs have been shown to optimize resource utilization, shorten hospitalization and prevent nosocomial infection. METHODS: We retrospectively analysed data regarding implementation of an HAH unit for caring patients with hematological malignancies in our center, during the COVID-19 pandemic. RESULTS: Between January and November 2020, 105 patients were treated in the HAH unit for a total of 204 episodes. Nine patients with multiple myeloma (MM) received autologous HSCT (auto-HSCT). Three patients with acute myeloid leukemia (AML) received consolidation therapy, 32 patients underwent clinical and analytical monitoring, 20 were transplant recipients early discharged (5 auto-HSCT and 15 allo-HSCT) and 2 had received CART cells therapy. Azacitidine, bortezomib and carfilzomib were administered at home to 54 patients with AML, myelodysplastic syndrome (MDS) or MM. A median of 17 (IQR 13-19) days of admission per patient and a total of 239 visits to the Hematology day-care hospital were avoided. Overall, 28 patients (14% of all episodes) needed admission to the hospital, 4 of them due to COVID-19. CONCLUSIONS: Implementation of a Hematology HAH unit was feasible and safe, and provided thorough advanced care to a high-risk population. Advanced care-at-home strategies can be crucial during times of COVID-19 to minimize treatment interruptions and reduce the risk of cross-infections.


Subject(s)
COVID-19 , Continuity of Patient Care , Hematologic Neoplasms/therapy , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Disease Management , Feasibility Studies , Female , Hematopoietic Stem Cell Transplantation , Hospitalization , Humans , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Multiple Myeloma/therapy , Myelodysplastic Syndromes/therapy , Retrospective Studies , Transplantation, Autologous , Young Adult
14.
Clin Cancer Res ; 27(16): 4468-4477, 2021 08 15.
Article in English | MEDLINE | ID: covidwho-1379685

ABSTRACT

Among the hallmarks of cancer is the ability of neoplastic cells to evade and suppress immune surveillance to allow their growth and evolution. Nowhere is this as apparent as in multiple myeloma, a cancer of antibody-producing plasma cells, where a complex interplay between neoplastic cells and the immune microenvironment is required for the development and progression of disease. Decades of research has led to the discovery of a number of therapeutic agents, from cytotoxic drugs to genetically engineered cells that mediate their antimyeloma effects at least partially through altering these immune interactions. In this review, we discuss the history of immunotherapy and current practices in multiple myeloma, as well as the advances that promise to one day offer a cure for this deadly disease.


Subject(s)
Immunotherapy , Multiple Myeloma/therapy , Humans , Multiple Myeloma/immunology
16.
Blood ; 138(9): 811-814, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1288619
18.
Transfus Apher Sci ; 60(5): 103197, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1275746

ABSTRACT

High-dose chemotherapy followed by autologous stem cell transplantation is a major component in the treatment of patients with multiple myeloma. As a prerequisite, the successful collection of a sufficient number of viable peripheral blood hematopoietic CD34+ cells is critical. A common standard protocol for mobilization is currently not defined and critically discussed especially in German-speaking Europe. In times of the Covid-19 pandemic, safe and effective strategies have to be chosen to minimize hospitalization times and severe courses. In this single-center retrospective analysis, safety and efficacy of cyclophosphamide plus etoposide (CE) and growth-factor support (n = 33) was compared to cyclophosphamide mono treatment and growth-factor support (n = 49) in 82 patients with multiple myeloma at first diagnosis. CE was superior to cyclophosphamide mono with a significantly higher number of collected CD34+ cells (15.46 × 106 CD34+ cells/kg vs. 9.92 × 106 CD34+ cells/kg), significantly faster engraftment of granulocytes after stem cell transplantation (day 10.5 vs. day 11.6), shorter duration of the inpatient stay (17.47 days vs. 19.16 days) and significantly less transfusions (8.82 % vs. 30.61 % patients receiving transfusions). The safety profile was comparable in both groups and in line with published data. We conclude that CE is a safe and highly effective mobilization protocol in patients with multiple myeloma at first diagnosis and appears to be superior to the commonly used cyclophosphamide mono regimen.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cyclophosphamide/pharmacology , Etoposide/pharmacology , Hematopoietic Stem Cell Mobilization/methods , Hematopoietic Stem Cells/drug effects , Multiple Myeloma/therapy , Peripheral Blood Stem Cell Transplantation/methods , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19 , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Granulocyte Colony-Stimulating Factor/pharmacology , Humans , Male , Melphalan/administration & dosage , Middle Aged , Multiple Myeloma/blood , Myeloma Proteins/analysis , Pandemics , Retrospective Studies , SARS-CoV-2 , Transplantation, Autologous
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