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5.
J Exp Med ; 218(3)2021 03 01.
Article in English | MEDLINE | ID: covidwho-1406442

ABSTRACT

The identification of discrete subclasses within the immunoglobulin G (IgG) isotype by Grey and Kunkel (1964. J. Exp. Med.https://doi.org/10.1084/jem.120.2.253) provided the framework for our current understanding of differential IgG subclass activity in protective and self-reactive immune responses.


Subject(s)
Immunoglobulin G/metabolism , Antibody Formation/immunology , B-Lymphocytes/metabolism , COVID-19/immunology , Glycosylation , Humans , Multiple Myeloma/immunology , Multiple Myeloma/pathology
6.
Blood Cancer J ; 11(8): 138, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338528

ABSTRACT

Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with either the BNT162b2 or the AZD1222 vaccine, on days 1 (before the first vaccine shot), 22, and 50. Patients with MM (n = 213), SMM (n = 38), and MGUS (n = 25) and 226 healthy controls were enrolled in the study (NCT04743388). Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p = 0.009) and on day 50 (p = 0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies (Mabs) or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination. In conclusion, MM patients have low humoral response following SARS-CoV-2 vaccination, especially under treatment with anti-CD38 or belamaf. This underlines the need for timely vaccination, possibly during a treatment-free period, and for continuous vigilance on infection control measures in non-responders.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Multiple Myeloma , SARS-CoV-2 , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Female , Humans , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/immunology , Prospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/metabolism
9.
Blood ; 138(9): 811-814, 2021 09 02.
Article in English | MEDLINE | ID: covidwho-1288619
11.
J Hematol Oncol ; 14(1): 81, 2021 05 17.
Article in English | MEDLINE | ID: covidwho-1232431

ABSTRACT

BACKGROUND: Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose. METHODS: Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher' exact test and the Mann-Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively. RESULTS: At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p < 0.001) and in disease cohorts with respect to controls (MM: p < 0.001 and MPM: p < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients (p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed. CONCLUSIONS: BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Multiple Myeloma/complications , Myeloproliferative Disorders/complications , Adult , Aged , Aged, 80 and over , COVID-19/immunology , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Immunogenicity, Vaccine , Immunoglobulin G/immunology , Male , Middle Aged , Multiple Myeloma/immunology , Myeloproliferative Disorders/immunology , Preliminary Data , Prospective Studies , SARS-CoV-2/immunology
14.
Eur J Haematol ; 105(6): 751-754, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-692706

ABSTRACT

COVID-19 has emerged as a global pandemic. Cancer patients have been reported to be at higher risk for adverse outcome of COVID-19. Studies are ongoing to decipher the risk factors and risk groups among cancer patients as well as strategies to refine treatment approaches. Here, we report eight patients with multiple myeloma that underwent immunomodulatory therapies with daratumumab or lenalidomide-based combination treatments and one patient with smoldering multiple myeloma, all of which presented with symptomatic COVID-19. We report that patients that succumbed to COVID-19 presented with either progressive tumor disease under daratumumab treatment or were in remission under lenalidomide-dexamethasone treatment.


Subject(s)
Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Coronavirus Infections/diagnosis , Dexamethasone/adverse effects , Lenalidomide/adverse effects , Multiple Myeloma/diagnosis , Pneumonia, Viral/diagnosis , Thalidomide/adverse effects , Antibodies, Monoclonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Betacoronavirus/pathogenicity , COVID-19 , Cohort Studies , Coronavirus Infections/drug therapy , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Dexamethasone/administration & dosage , Disease Progression , Female , Humans , Immunomodulation , Lenalidomide/administration & dosage , Male , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Multiple Myeloma/mortality , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Prognosis , Remission Induction , SARS-CoV-2 , Severity of Illness Index , Survival Analysis , Thalidomide/administration & dosage , Treatment Outcome
15.
J Hematol Oncol ; 13(1): 94, 2020 07 14.
Article in English | MEDLINE | ID: covidwho-647080

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by SARS-CoV-2 virus, has resulted in over 100,000 deaths in the USA. Our institution has treated over 2000 COVID-19 patients during the pandemic in New York City. The pandemic directly impacted cancer patients and the organization of cancer care. Mount Sinai Hospital has a large and diverse multiple myeloma (MM) population. Herein, we report the characteristics of COVID-19 infection and serological response in MM patients in a large tertiary care institution in New York. METHODS: We performed a retrospective study on a cohort of 58 patients with a plasma-cell disorder (54 MM, 4 smoldering MM) who developed COVID-19 between March 1, 2020, and April 30, 2020. We report epidemiological, clinical, and laboratory characteristics including the persistence of viral detection by polymerase chain reaction (PCR) and anti-SARS-CoV-2 antibody testing, treatments initiated, and outcomes. RESULTS: Of the 58 patients diagnosed with COVID-19, 36 were hospitalized and 22 were managed at home. The median age was 67 years; 52% of patients were male and 63% were non-White. Hypertension (64%), hyperlipidemia (62%), obesity (37%), diabetes mellitus (28%), chronic kidney disease (24%), and lung disease (21%) were the most common comorbidities. In the total cohort, 14 patients (24%) died. Older age (> 70 years), male sex, cardiovascular risk, and patients not in complete remission (CR) or stringent CR were significantly (p < 0.05) associated with hospitalization. Among hospitalized patients, laboratory findings demonstrated elevation of traditional inflammatory markers (CRP, ferritin, D-dimer) and a significant (p < 0.05) association between elevated inflammatory markers, severe hypogammaglobulinemia, non-White race, and mortality. Ninety-six percent (22/23) of patients developed antibodies to SARS-CoV-2 at a median of 32 days after initial diagnosis. The median time to PCR negativity was 43 (range 19-68) days from initial positive PCR. CONCLUSIONS: Drug exposure and MM disease status at the time of contracting COVID-19 had no bearing on mortality. Mounting a severe inflammatory response to SARS-CoV-2 and severe hypogammaglobulinemia was associated with higher mortality. The majority of patients mounted an antibody response to SARS-CoV-2. These findings pave a path to the identification of vulnerable MM patients who need early intervention to improve outcomes in future outbreaks of COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Multiple Myeloma/complications , Pneumonia, Viral/complications , Tertiary Care Centers , Agammaglobulinemia/mortality , Agammaglobulinemia/pathology , Aged , COVID-19 , Cohort Studies , Coronavirus Infections/mortality , Female , Humans , Immunocompromised Host , Inflammation/mortality , Inflammation/pathology , Male , Middle Aged , Multiple Myeloma/immunology , New York City/epidemiology , Pandemics , Pneumonia, Viral/mortality , Retrospective Studies , Risk Factors , SARS-CoV-2
16.
Intern Med J ; 50(6): 667-679, 2020 06.
Article in English | MEDLINE | ID: covidwho-271531

ABSTRACT

The COVID-19 pandemic poses a unique challenge to the care of patients with haematological malignancies. Viral pneumonia is known to cause disproportionately severe disease in patients with cancer, and patients with lymphoma, myeloma and chronic lymphocytic leukaemia are likely to be at particular risk of severe disease related to COVID-19. This statement has been developed by consensus among authors from Australia and New Zealand. We aim to provide supportive guidance to clinicians making individual patient decisions during the COVID-19 pandemic, in particular during periods that access to healthcare resources may be limited. General recommendations include those to minimise patient exposure to COVID-19, including the use of telehealth, avoidance of non-essential visits and minimisation of time spent by patients in infusion suites and other clinical areas. This statement also provides recommendations where appropriate in assessing indications for therapy, reducing therapy-associated immunosuppression and reducing healthcare utilisation in patients with specific haematological malignancies during the COVID-19 pandemic. Specific decisions regarding therapy of haematological malignancies will need to be individualised, based on disease risk, risks of immunosuppression, rates of community transmission of COVID-19 and available local healthcare resources.


Subject(s)
Consensus , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Infection Control/methods , Leukemia, Lymphocytic, Chronic, B-Cell/physiopathology , Lymphoma/physiopathology , Multiple Myeloma/physiopathology , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , Australia , Betacoronavirus/immunology , COVID-19 , Comorbidity , Coronavirus Infections/immunology , Coronavirus Infections/virology , Drug Therapy , Guideline Adherence , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Lymphoma/immunology , Lymphoma/therapy , Multiple Myeloma/immunology , Multiple Myeloma/therapy , New Zealand , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Practice Guidelines as Topic , Risk Assessment , SARS-CoV-2 , Salvage Therapy/methods , Stem Cell Transplantation/methods
17.
Acta Haematol ; 143(5): 410-416, 2020.
Article in English | MEDLINE | ID: covidwho-94334

ABSTRACT

We provide our recommendations (not evidence based) for managing multiple myeloma patients during the pandemic of COVID-19. We do not recommend therapy for smoldering myeloma patients (standard or high risk). Screening for COVID-19 should be done in all patients before therapy. For standard-risk patients, we recommend the following: ixazomib, lenalidomide, and dexamethasone (IRd) (preferred), cyclophosphamide lenalidomide and dexamethasone (CRd), daratumumab lenalidomide and dexamethasone (DRd), lenalidomide, bortezomib, and dexamethasone (RVd), or cyclophosphamide, bortezomib, and dexamethasone (CyBorD). For high-risk patients we recommend carfilzomib, lenalidomide, and dexamethasone (KRd) (preferred) or RVd. Decreasing the dose of dexamethasone to 20 mg and giving bortezomib subcutaneously once a week is recommended. We recommend delaying autologous stem cell transplant (ASCT), unless the patient has high-risk disease that is not responding well, or if the patient has plasma cell leukemia (PCL). Testing for COVID-19 should be done before ASCT. If a patient achieves a very good partial response or better, doses and frequency of drug administration can be modified. After 10-12 cycles, lenalidomide maintenance is recommended for standard-risk patients and bortezomib or ixazomib are recommended for high-risk patients. Daratumumab-based regimens are recommended for relapsed patients. Routine ASCT is not recommended for relapse during the epidemic unless the patient has an aggressive relapse or secondary PCL. Patients on current maintenance should continue their therapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphopenia/therapy , Multiple Myeloma/therapy , Pandemics , Betacoronavirus/immunology , Betacoronavirus/pathogenicity , COVID-19 , Clinical Decision-Making , Coronavirus Infections/epidemiology , Coronavirus Infections/immunology , Coronavirus Infections/virology , Dexamethasone/therapeutic use , Disease Management , Hematopoietic Stem Cell Transplantation/methods , Humans , Lymphopenia/epidemiology , Lymphopenia/immunology , Lymphopenia/virology , Multiple Myeloma/epidemiology , Multiple Myeloma/immunology , Multiple Myeloma/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , Risk Assessment , SARS-CoV-2 , Time Factors , Transplantation, Autologous
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