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2.
Blood Cancer Discov ; 2(6): 568-576, 2021 11.
Article in English | MEDLINE | ID: covidwho-1518189

ABSTRACT

Coronavirus disease-19 (COVID-19) vaccine response data for patients with hematologic malignancy, who carry high risk for severe COVID-19 illness, are incomplete. In a study of 551 hematologic malignancy patients with leukemia, lymphoma, and multiple myeloma, anti-SARS-CoV-2 spike IgG titers and neutralizing activity were measured at 1 and 3 months from initial vaccination. Compared with healthy controls, patients with hematologic malignancy had attenuated antibody titers at 1 and 3 months. Furthermore, patients with hematologic malignancy had markedly diminished neutralizing capacity of 26.3% at 1 month and 43.6% at 3 months, despite positive seroconversion rates of 51.5% and 68.9% at the respective time points. Healthy controls had 93.2% and 100% neutralizing capacity at 1 and 3 months, respectively. Patients with leukemia, lymphoma, and multiple myeloma on observation had uniformly blunted responses. Treatment with Bruton tyrosine kinase inhibitors, venetoclax, phosphoinositide 3-kinase inhibitors, anti-CD19/CD20-directed therapies, and anti-CD38/B-cell maturation antigen-directed therapies substantially hindered responses, but single-agent immunomodulatory agents did not. Significance: Patients with hematologic malignancy have compromised COVID-19 vaccine responses at baseline that are further suppressed by active therapy, with many patients having insufficient neutralizing capacity despite positive antibody titers. Refining vaccine response parameters is critical to guiding clinical care, including the indication for booster vaccines, for this vulnerable population.See related article by Tamari et al., p. 577. This article is highlighted in the In This Issue feature, p. 549.


Subject(s)
COVID-19 , Hematologic Neoplasms , BNT162 Vaccine , COVID-19 Vaccines , Humans , Immunity, Humoral , Phosphatidylinositol 3-Kinases , SARS-CoV-2 , Vaccination
3.
Blood ; 138(18): 1768-1773, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1322916
4.
Leuk Lymphoma ; 62(8): 1940-1948, 2021 08.
Article in English | MEDLINE | ID: covidwho-1284804

ABSTRACT

Patients with hematological malignancies are at risk for poor outcomes when diagnosed with coronavirus disease 2019 (COVID-19). It remains unclear whether cytopenias and specific leukemia subtypes play a role in the clinical course of COVID-19 infection. Here, we report outcomes and their clinical/laboratory predictors for 65 patients with acute and chronic leukemias diagnosed with COVID-19 between 8 March 2020 and 19 May 2020 at Memorial Sloan Kettering Cancer Center in New York City. Most patients had CLL (38%) or AML (26%). A total of 14 (22%) patients required high flow nasal cannula or were intubated for mechanical ventilation and 11 patients (17%) died. A diagnosis of AML (OR 4.7, p=.028), active treatment within the last 3 months (OR 5.22, p=.047), neutropenia within seven days prior and up to 28 days after SARS-CoV-2 diagnosis (11.75, p=.001) and ≥3 comorbidities (OR 6.55, p=.019) were associated with increased odds of death.


Subject(s)
COVID-19 , Leukemia, Myeloid, Acute , Neutropenia , Adult , COVID-19 Testing , Humans , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/epidemiology , Leukemia, Myeloid, Acute/therapy , Neutropenia/epidemiology , Neutropenia/etiology , Risk Factors , SARS-CoV-2
7.
Clin Cancer Res ; 26(14): 3514-3516, 2020 07 15.
Article in English | MEDLINE | ID: covidwho-693869

ABSTRACT

As the SARS-CoV-2 (COVID-19) pandemic spreads and the number of Bruton's tyrosine kinase inhibitor (BTKi)-treated COVID-19-affected patients grows, we must consider the pros and cons of BTKi discontinuation for our patients. In favor of BTKi continuation, BTK plays an active role in macrophage polarization. By modulating key transcription factors, BTK may regulate macrophage polarization downstream of classic M1 and M2 polarizing stimuli and mitigate the hyperinflammatory state associated with COVID-19. In favor of BTKi discontinuation, we note a potentially increased risk of secondary infections and impaired humoral immunity. We hypothesize that the potential benefit of blunting a hyperinflammatory response to SARS-CoV-2 through attenuation of M1 polarization outweighs the potential risk of impaired humoral immunity, not to mention the risk of rapid progression of B-cell malignancy following BTKi interruption. On the basis of this, we suggest continuing BTKi in patients with COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Coronavirus Infections/drug therapy , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Lymphoma, B-Cell/drug therapy , Pneumonia, Viral/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adenine/analogs & derivatives , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Anti-Inflammatory Agents/adverse effects , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Benzamides/therapeutic use , Betacoronavirus/drug effects , COVID-19 , Coronavirus Infections/pathology , Humans , Inflammation/prevention & control , Macrophages/immunology , Pandemics , Piperidines/therapeutic use , Pneumonia, Viral/pathology , Protein Kinase Inhibitors/adverse effects , Pyrazines/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , SARS-CoV-2
8.
Blood ; 136(10): 1134-1143, 2020 09 03.
Article in English | MEDLINE | ID: covidwho-656981

ABSTRACT

Given advanced age, comorbidities, and immune dysfunction, chronic lymphocytic leukemia (CLL) patients may be at particularly high risk of infection and poor outcomes related to coronavirus disease 2019 (COVID-19). Robust analysis of outcomes for CLL patients, particularly examining effects of baseline characteristics and CLL-directed therapy, is critical to optimally manage CLL patients through this evolving pandemic. CLL patients diagnosed with symptomatic COVID-19 across 43 international centers (n = 198) were included. Hospital admission occurred in 90%. Median age at COVID-19 diagnosis was 70.5 years. Median Cumulative Illness Rating Scale score was 8 (range, 4-32). Thirty-nine percent were treatment naive ("watch and wait"), while 61% had received ≥1 CLL-directed therapy (median, 2; range, 1-8). Ninety patients (45%) were receiving active CLL therapy at COVID-19 diagnosis, most commonly Bruton tyrosine kinase inhibitors (BTKi's; n = 68/90 [76%]). At a median follow-up of 16 days, the overall case fatality rate was 33%, though 25% remain admitted. Watch-and-wait and treated cohorts had similar rates of admission (89% vs 90%), intensive care unit admission (35% vs 36%), intubation (33% vs 25%), and mortality (37% vs 32%). CLL-directed treatment with BTKi's at COVID-19 diagnosis did not impact survival (case fatality rate, 34% vs 35%), though the BTKi was held during the COVID-19 course for most patients. These data suggest that the subgroup of CLL patients admitted with COVID-19, regardless of disease phase or treatment status, are at high risk of death. Future epidemiologic studies are needed to assess severe acute respiratory syndrome coronavirus 2 infection risk, these data should be validated independently, and randomized studies of BTKi's in COVID-19 are needed to provide definitive evidence of benefit.


Subject(s)
Coronavirus Infections/complications , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pneumonia, Viral/complications , Adult , Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors , Aged , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/therapy , Female , Humans , Immunization, Passive , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Male , Middle Aged , Pandemics , Pneumonia, Viral/therapy , Protein Kinase Inhibitors/therapeutic use , SARS-CoV-2 , Survival Analysis , Treatment Outcome , COVID-19 Serotherapy
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