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1.
Blood Cancer Discov ; 3(3): 181-193, 2022 05 05.
Article in English | MEDLINE | ID: covidwho-1883342

ABSTRACT

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19. SIGNIFICANCE: Our study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171.


Subject(s)
COVID-19 , Lymphatic Diseases , Neoplasms , COVID-19/epidemiology , COVID-19 Testing , Humans , Neoplasms/epidemiology , Risk Factors , SARS-CoV-2
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-322672

ABSTRACT

Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19;however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one cancer patients underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies (82%), patients that received anti-CD-20 antibody therapy (59%), CAR-T/cellular therapy (33%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic

4.
Acta Haematol ; 145(3): 244-256, 2022.
Article in English | MEDLINE | ID: covidwho-1673577

ABSTRACT

Patients with hematologic malignancies are particularly vulnerable to infections due to underlying humoral and cellular immune dysfunction, cytotoxic chemotherapy regimens, advanced age, and the presence of comorbid conditions. Infection from severe acute respiratory syndrome coronavirus 2, the causative agent of the COVID-19 pandemic, has become a leading cause of death globally and has disproportionally affected this high-risk population. Here, we review the cumulative evidence demonstrating worse outcomes for patients with hematologic malignancies when compared to patients with solid tumors and the general population. We examine risk factors shared with the general population (age, sex, comorbid conditions, and race) and those that are cancer-specific (cytotoxic chemotherapy, progressive disease, and cancer type), all of which confer an increased risk of severe COVID-19. Despite the historical exclusion of cancer patients from COVID-19 therapy trials, we review the emerging evidence that patients with hematologic malignancies benefit from specific treatments such as convalescent plasma. Although COVID-19 vaccines are significantly less effective in this patient population, encouraging results are observed in a subset of these patients after receiving a booster dose.


Subject(s)
COVID-19 , Hematologic Neoplasms , Neoplasms , COVID-19/complications , COVID-19/therapy , COVID-19 Vaccines , Hematologic Neoplasms/complications , Hematologic Neoplasms/epidemiology , Hematologic Neoplasms/therapy , Humans , Immunization, Passive , Pandemics
5.
Cancer Cell ; 40(1): 3-5, 2022 01 10.
Article in English | MEDLINE | ID: covidwho-1517077

ABSTRACT

Anti-COVID-19 immunity dynamics were assessed in patients with cancer in a prospective clinical trial. Waning of immunity was detected 4-6 months post-vaccination with significant increases in anti-spike IgG titers after booster dosing, and 56% of seronegative patients seroconverted post-booster vaccination. Prior anti-CD20/BTK inhibitor therapy was associated with reduced vaccine efficacy.


Subject(s)
Antibodies, Viral/biosynthesis , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunization, Secondary , Immunoglobulin G/biosynthesis , Neoplasms/immunology , SARS-CoV-2/immunology , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antigens, Viral/immunology , COVID-19/complications , COVID-19/immunology , Follow-Up Studies , Humans , Immunocompromised Host , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Neoplasms/complications , Neoplasms/drug therapy , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Rituximab/adverse effects , Rituximab/therapeutic use , Seroconversion , Spike Glycoprotein, Coronavirus/immunology , Vaccination
6.
Nat Cancer ; 2(4): 392-399, 2021 04.
Article in English | MEDLINE | ID: covidwho-1475490

ABSTRACT

Patients with cancer have been identified in several studies to be at high risk of developing severe COVID-19; however, rates of SARS-CoV-2 IgG seroconversion and its association with cancer types and anti-cancer therapy remain obscure. We conducted a retrospective cohort study in patients with cancer that underwent SARS-CoV-2 IgG testing. Two hundred and sixty-one patients with a cancer diagnosis underwent SARS-CoV-2 IgG testing and demonstrated a high rate of seroconversion (92%). However, significantly lower seroconversion was observed in patients with hematologic malignancies (82%), patients that received anti-CD-20 antibody therapy (59%) and stem cell transplant (60%). Interestingly, all 17 patients that received immunotherapy, including 16 that received anti-PD-1/PD-L1 monoclonal antibodies, developed SARS-Cov-2 IgG antibodies (100% seroconversion). These data show differential rates of seroconversion in specific patient groups and bear importance for clinical monitoring and vaccination strategies that are being developed to mitigate the COVID-19 pandemic.


Subject(s)
Antibodies, Viral/blood , Immunoglobulin G/blood , Neoplasms/immunology , SARS-CoV-2/immunology , Seroconversion , Adult , Aged , Aged, 80 and over , COVID-19 Nucleic Acid Testing , Female , Humans , Male , Middle Aged , Neoplasms/drug therapy , Retrospective Studies , Young Adult
7.
Cancer Cell ; 39(8): 1081-1090.e2, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1343145

ABSTRACT

As COVID-19 adversely affects patients with cancer, prophylactic strategies are critically needed. Using a validated antibody assay against SARS-CoV-2 spike protein, we determined a high seroconversion rate (94%) in 200 patients with cancer in New York City that had received full dosing with one of the FDA-approved COVID-19 vaccines. On comparison with solid tumors (98%), a significantly lower rate of seroconversion was observed in patients with hematologic malignancies (85%), particularly recipients following highly immunosuppressive therapies such as anti-CD20 therapies (70%) and stem cell transplantation (73%). Patients receiving immune checkpoint inhibitor therapy (97%) or hormonal therapies (100%) demonstrated high seroconversion post vaccination. Patients with prior COVID-19 infection demonstrated higher anti-spike IgG titers post vaccination. Relatively lower IgG titers were observed following vaccination with the adenoviral than with mRNA-based vaccines. These data demonstrate generally high immunogenicity of COVID-19 vaccination in oncology patients and identify immunosuppressed cohorts that need novel vaccination or passive immunization strategies.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Neoplasms/complications , Neoplasms/immunology , SARS-CoV-2/immunology , Seroconversion , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/epidemiology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Female , Host-Pathogen Interactions/immunology , Humans , Immunogenicity, Vaccine , Immunoglobulin G/blood , Immunoglobulin G/immunology , Male , Middle Aged , Neoplasms/epidemiology , Neoplasms/therapy , Public Health Surveillance , Risk Factors , Spike Glycoprotein, Coronavirus/blood , Spike Glycoprotein, Coronavirus/immunology , Vaccination
8.
Blood ; 136(Supplement 1):28-30, 2020.
Article in English | PMC | ID: covidwho-1339054

ABSTRACT

Background: Patients with hematologic malignancy (HM) are hypothesized to be at high risk of poor outcomes with coronavirus disease 2019 (COVID-19), due to disease and therapy-related immunosuppression. Despite this, there are minimal reported data describing the outcomes of HM patients with COVID-19.Methods: The COVID-19 and Cancer Consortium (CCC19) (NCT04354701) is an international registry aimed at investigating the clinical course and complications of COVID-19 in patients with cancer. The CCC19 cohort includes patients with active cancer or a history of cancer with presumed or laboratory-confirmed COVID-19. The registry contains de-identified patient demographics, information regarding cancer diagnosis and treatment history, COVID-19 treatments, and clinical outcomes. Patients greater than 18 years of age with laboratory-confirmed, symptomatic COVID-19 and HM diagnoses were included in this study. The primary outcome is a composite of severe COVID-19 illness (composed of mechanical ventilation, severe illness requiring hospitalization, intensive care unit (ICU) requirement, or death);mechanical ventilation, ICU level of care, supplemental oxygen, and 30-day mortality are reported as secondary outcomes. Baseline characteristics are reported for the entire cohort. Reported clinical outcomes are stratified by cancer type, cancer status, line of therapy received (never treated, first, second or later), receipt of cellular therapy or transplant (none, within 12 months, >12 months prior to COVID-19 diagnosis), last receipt of cytotoxic therapy (within 4 weeks, 1-3 months, 3-12 months prior to COVID-19 diagnosis), and receipt of HM therapies under investigation as repurposed treatments for COVID-19 (Bruton tyrosine kinase (BTK) inhibitors, Janus kinase (JAK) inhibitors, Bcr-Abl kinase inhibitors).Results: From March 17, 2020 to July 31, 2020, a total of 757 patients with HM and COVID-19 were enrolled and met inclusion criteria. Median follow-up was 30 days (IQR 17-70 days). Median age was 65 years (IQR 55-75), 62% (470) were over age 60, 57% were men, 45% were non-Hispanic white (22% Black, 18% Hispanic, 5% other), 39% were former or current smokers, 27% were obese, 18% had Eastern Cooperative Oncology Group (ECOG) performance status ≥2, and 51% were on active treatment within 3 months of COVID-19 diagnosis.Among patients with HM, 281 (37%) developed the primary endpoint. Five-hundred and eleven patients (67%) were hospitalized (some with non-severe disease), 188 (25%) required ICU level of care, 133 (18%) required mechanical ventilation, 409 (54%) required supplemental oxygen, and 143 (19%) died within 30 days of COVID-19 diagnosis. Stratified rates of severe outcomes are shown in the Table. The rate of severe COVID-19 was highest in patients with chronic lymphocytic leukemia (53%), and lowest in patients with Hodgkin lymphoma (23%). Patients receiving cytotoxic systemic therapy within 3 months of COVID-19 diagnosis had higher rates of severe COVID-19 (41%) and 30-day mortality (28%) than patients who completed treatment 3-12 months (26% severe COVID-19, 16% 30-day mortality) or more than 12 months (29% severe COVID-19, 13% 30-day mortality) prior to COVID-19 diagnosis. Patients receiving cellular therapy or transplant within a year prior to COVID-19 diagnosis had similar rates of severe COVID-19 (36% v. 38%) and 30-day mortality (23% v. 19%) to patients who had not received such therapies within a year prior to COVID-19 diagnosis. Patients on second-line or later therapy experienced similar rates of poor outcomes (42% severe COVID-19, 20% 30-day mortality) to patients on first-line therapy (39% severe COVID-19, 18% 30-day mortality) and untreated patients (42% severe COVID-19, 20% 30-day mortality). Outcomes for patients receiving therapies under investigation as repurposed COVID-19 treatments were similar to the cohort at large.Conclusions: This is the largest cohort study to date describing COVID-19 outcomes in patients with HM. Rates of severe COVID-19 outcomes including death were high. Unadjusted rates o severe COVID-19 outcomes were higher in patients with previously described risk factors such as advanced age, poor performance status, and progressive disease, as well as those receiving recent cytotoxic therapy. Outcomes varied widely by malignancy but were similar across treatment contexts. Additional data collection and analyses are ongoing.

9.
Blood ; 136(Supplement 1):34-35, 2020.
Article in English | PMC | ID: covidwho-1339000

ABSTRACT

Introduction:We sought to compare outcomes among patients with hematologic neoplasms diagnosed with COVID-19 infection in a multiethnic urban academic medical center.Methods:A retrospective analysis of patients with hematologic neoplasms diagnosed with COVID-19 from March 17th to June 8th2020 was conducted. Subjects included were censored at last point of contact. Variables collected included age, gender, race/ethnicity, hematologic diagnosis, cancer treatment status, baseline and follow-up COVID-19 testing, neutrophil count, and lymphocyte count at time of diagnosis. Associations between hematologic diagnosis, cancer treatment status, age, gender, race/ethnicity, neutrophil-to-lymphocyte ratio (NLR), and overall survival (OS) were assessed using the Kaplan-Meier method with logrank test.Results:A total of 102 subjects with hematologic neoplasms and COVID-19 infection treated in Montefiore Health system were identified (Table 1). Thirty-nine (38%) subjects were undergoing active treatment, including 17 (16%) receiving conventional chemotherapy agents, 12 (12%) targeted therapy, and 10 (10%) combination therapy. Of those subjects, twenty (50%) experienced delay or discontinuation of treatment due to COVID-19 infection. Four subjects (4%) showed persistent infection by PCR at median duration of 25.1 days after initial diagnosis. Ten subjects (9.8%) showed clearance of the virus by PCR with median time-to-clearance of 51.8 days. Of 9 subjects with serologic testing, 8 tested positive for COVID-19 IgG antibody at median time of 62 days after initial COVID-19 diagnosis. Forty-seven (47%) subjects expired as a result of COVID-19 disease at the time of analysis. Disease type, treatment status, race/ethnicity, age, and gender showed no significant association with mortality. Patients older than 70 had worse outcomes than the younger population (p = 0.0082). Median neutrophil and lymphocyte count at time of diagnosis was 4500 and 900, respectively. NLR greater than 9 was associated with worse survival when compared to NLR less than 9 (p=0.0067).Conclusions:COVID-19 infection has adverse effects on patients with hematological neoplasms. Subjects older than 70 years had a significantly worse prognosis. Notably, subjects actively being treated with chemotherapy did not have worse outcomes than those not being treated in our cohort, supporting the notion than active COVID-19 infection per se should not result in treatment delays. In addition, high NLR correlates with worsened survival, suggesting that this could be a potential prognostic factor for COVID-19 mortality in the hematologic neoplasms population.

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