ABSTRACT
Background: Recent studies reported low rates of seroconversion response to COVID-19 vaccination in patients (pts) with hematologic malignancies (HMs). Vaccine choice among the 3 FDA-authorized products (BNT162b2/Pfizer-BioNTech, mRNA-1273/Moderna, or Ad26.COV2.S/J&J), prior therapy, and disease-specific factors may affect seroconversion. Addressing these factors may improve seroconversion rates and identify pts at risk of severe COVID-19 infection despite vaccination. Methods: We conducted a retrospective study of adults with HMs vaccinated in our center between 2/2021 and 7/2021, excluding pts with prior COVID-19 infection. Seroconversion was assessed by the qualitative SARS-CoV-2 Total Antibody Test (IgG/IgM against Receptor Binding Domain [RBD], Wondfo USA, Willowbrook, IL). A subset of samples was tested by the semi-quantitative Abbott AdviseDx SARS-CoV-2 IgG II assay (IgG against RBD). For univariate associations (UVA) we used Fisher's exact test for categorical variables, and fractional polynomial fits for continuous variables to examine non-linearity. Multivariable analysis (MVA) used a robust Poisson model reporting risk ratio (RR) with 95% confidence intervals (CI). Results: Among 239 eligible pts, median age was 70 (range, 28-94), and 112 (47%) were female. HMs included aggressive B-cell lymphomas (n=74, 31%), indolent B-cell lymphomas (n=52, 22%), chronic lymphocytic leukemia (CLL, n=30, 13%), other lymphomas (n-19, 8%), plasma cell neoplasms (n=43, 18%), and myeloid cancers (n=21, 9%);140 pts (59%) received BNT162b2/Pfizer, 74 (31%) mRNA-1273/Moderna, and 23 (10%) Ad26.COV2.S/J&J vaccines (2 pts had undetermined vaccine type). HM was active in 100 pts (42%), whereas 108 (45%) pts were in remission after treatment, and 31 (13%) on watchful waiting (WW, never treated);141 (59%) had a prior exposure to an anti-B-cell monoclonal antibody, and 22 (9%) prior stem cell transplantation. Overall, 99 pts (41%;binomial 95% CI, 35-48%) showed post-vaccination seroconversion upon testing at median 10 weeks from first vaccine. Seroconversion was significantly less frequent among pts with lymphomas compared with plasma cell or myeloid neoplasms (overall P=.020;Fig A). It was also less frequent after prior anti-B-cell antibody exposure (29% vs 59%, P<.0001;Fig. B), and in those with active disease (28%, vs 49% for remission [P=.0027], vs 58% for WW [P=.0045];Fig. C). Furthermore, seroconversion was significantly more frequent after mRNA-1273/Moderna vaccine (57%) compared with BNT162b2/Pfizer (36%, P=.006) or Ad26.COV2.S/J&J (22%, P=.004;Fig. D). It was not associated with age (Fig. E), WBC (Fig. G), or time from vaccination (Fig. I), but was significantly higher with increased lymphocyte count (P<.0001;Fig F) and time elapsed from last chemotherapy (P=.0039;Fig. H). In a MVA (Fig. J), vaccination with mRNA-1273 remained significantly associated with higher rate of seroconversion compared with BNT162b2 (RR=0.59;95%CI, 0.44-0.79) or Ad26.COV2.S (RR=0.35;95%CI, 0.16-0.77). Higher seroconversion rate was also associated with remission (RR=1.98;95%CI, 1.42-2.76) or WW status (RR=1.72;95%CI 1.02-2.89) compared with active disease, and higher lymphocyte count. Exposure to anti-B-cell antibodies remained associated with lack of seroconversion (RR=0.66;95%CI, 0.44-0.99). Seroconversion was borderline less frequent in CLL than lymphomas, and higher with plasma cell or myeloid disorders. Results were similar in the subset of pts (n=191) with prior treatment, adjusting for time from last chemotherapy(data not shown). The anti-COVID-19 IgG titers on semiquantitative test (n=47, all after mRNA-based vaccines) were also lower in pts with active disease compared with those in remission (P=.065) or under WW (P=.028), and in those with prior anti-B-cell antibody (P=.0095). Conclusions: Pts with HMs demonstrate overall low rates of seroconversion after vaccination against COVID-19, particularly when they have active disease or are on/after B-cell depleting monoclonal antibody therapy. The mRNA vaccines (particularly mRNA- 273) appear to have elicited superior responses compared with the adenovirus-based product. Pts with active HMs or those within 2 years of last therapy should be particularly aware of the risk of infection despite vaccines and should be considered for strategies to enhance anti-COVID-19 immunity regardless of age. [Formula presented] Disclosures: Olszewski: TG Therapeutics: Research Funding;PrecisionBio: Research Funding;Celldex Therapeutics: Research Funding;Acrotech Pharma: Research Funding;Genentech, Inc.: Research Funding;Genmab: Research Funding.
ABSTRACT
Background: Early reports suggested that cancer patients have a 1.7-fold increased risk of contracting SARS-CoV-2 and higher rates of severe events and mortality compared with general population. Patients with hematologic malignancies may have worse COVID-19 outcomes, due to an impaired humoral immune response from their underlying malignancy and concurrent anticancer therapy. In this multi-center, retrospective, observational study, we evaluate the associations of COVID-19 outcomes with patient and lymphoma disease characteristics. Methods: EMRs at 10 study centers across the USA identified 519 patients with a diagnosis of lymphoma, CLL, or other lymphoid malignancies, who had a documented positive result of SARS-CoV-2 PCR or nucleocapsid antibody testing. Descriptive statistics were used to summarize the demographic and clinical characteristics. Logistic regression was used to evaluate the associations of individual characteristics with COVID-19 outcomes, adjusted for center (NYU vs. other). The interactions between each of the variables was also included in these models;since the interactions were generally small and non-significant, only the main effect of center was included. Two-sided p-values ≤0.05 were considered significant;there were no adjustments for multiple variables or endpoints. Each analysis was based on complete data for that analysis. Results: Tables 1 and 2 provide demographic and clinical characteristics, respectively, of the 519 patients. The mean age was 61.9 years, with 296 (57%) male and 374 (72%) white patients. NYU had the largest cohort (318 patients), with the remaining centers contributing a range of 3 to 69 patients (median 14). Logistic regression models for the association of each COVID-19 outcome with individual clinical and patient characteristics included adjustments for the center (NYU/other). While center effects were statistically significant, center by covariate interaction effects were not and are not included in the final models. The odds ratio (OR) estimates and p-values for each patient and CLL/lymphoma clinical variable are shown in Tables 3 and 4, respectively. The risks of experiencing a severe event, death, and hospital admission increased with age;for each 10 years of age increase, the ORs were 1.58 for experiencing severe events, 1.78 for death, and 1.65 for hospital admission. The risks of poor outcome were higher in males than in females (OR 1.93 for severe events, 1.85 for death, and 1.47 for hospital admission). Patients with Charlson Comorbidity Index (CCI) >5 had a higher risk of severe events (OR 2.46), mortality (3.30) and hospital admission (2.73) compared to patients with CCI ≤5. Compared to patients with HL, patients with aggressive NHL had a higher risk of severe events (OR 4.05), mortality (4.68) and hospital admission (4.65). Patients with CLL similarly had a higher risk of severe events (OR 4.64), mortality (4.65) and hospital admission (5.93) compared to HL patients. Patients with indolent NHL had a higher risk of hospital admission (OR 3.95) but not a higher risk of mortality compared to HL. Patients in remission at the time of COVID-19 diagnosis had a lower risk of severe events (OR 0.42), mortality (0.36) and hospital admission (0.40) relative to those who were not in remission. Patients who received cytotoxic chemotherapy within 28 days of their COVID-19 diagnosis had a higher risk of severe events (OR 2.54), mortality (2.79), and hospital admission (2.31). Patients who received an anti-CD20 monoclonal antibody within 6 months of COVID-19 diagnosis had a higher risk of severe events (OR 2.60), mortality (2.17) and hospital admission (3.28). Conclusions: In addition to demographic and comorbidity risk factors identified in previous studies, our study shows that patients with aggressive NHL and CLL, or patients who have received recent cytotoxic chemotherapy or anti-CD20 mAB, may be at risk for poor COVID-19 outcome. The difference in risk between NHL and HL patients is likely associated with young age of HL patients but may also be related o differences in underlying innate and adaptive immune defects. Patients at high risk for poor outcome should be a priority for studies of monoclonal antibody prophylaxis. If defects in humoral immunity are at the root of poor outcome, this may be compounded by poor response to vaccination. Multivariate analysis of this data will be completed in advance of the meeting. [Formula presented] Disclosures: Olszewski: Celldex Therapeutics: Research Funding;PrecisionBio: Research Funding;TG Therapeutics: Research Funding;Acrotech Pharma: Research Funding;Genentech, Inc.: Research Funding;Genmab: Research Funding. Barta: Daiichi Sankyo: Honoraria;Seagen: Honoraria;Acrotech: Honoraria;Kyowa Kirin: Honoraria. Hernandez-Ilizaliturri: AbbVie: Other: Advisory Boards;Incyte: Other: Advisory Boards;Celgene: Other: Advisory Boards;BMS: Other: Advisory Boards;Pharmacyclics: Other: Advisory Boards;Amgen: Other: Advisory Boards;Kite: Other: Advisory Boards;Gilead: Other: Advisory Boards;Epyzime: Other: Advisory Boards. Leslie: Janssen: Consultancy, Speakers Bureau;Merck: Consultancy;Abbvie: Consultancy, Honoraria;Epizyme: Consultancy, Honoraria, Speakers Bureau;PCYC/Janssen: Consultancy, Honoraria, Speakers Bureau;Seagen: Consultancy, Honoraria, Speakers Bureau;TG Therapeutics: Consultancy, Honoraria, Speakers Bureau;Celgene/BMS: Consultancy, Honoraria, Speakers Bureau;Kite, a Gilead Company: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy;BeiGene: Consultancy, Honoraria, Speakers Bureau;Karyopharm Therapeutics: Honoraria, Speakers Bureau;AstraZeneca: Consultancy, Honoraria, Speakers Bureau;Pharmacyclics: Consultancy, Honoraria, Speakers Bureau. Diefenbach: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding;Merck Sharp & Dohme: Consultancy, Honoraria, Research Funding;Morphosys: Consultancy, Honoraria, Research Funding;Genentech, Inc./ F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Research Funding;Perlmutter Cancer Center at NYU Langone Health: Current Employment;Incyte: Research Funding;AbbVie: Research Funding;Trillium: Research Funding;IGM Biosciences: Research Funding;IMab: Research Funding;Janssen: Consultancy, Honoraria, Research Funding;Gilead: Current equity holder in publicly-traded company;MEI: Consultancy, Research Funding;Celgene: Research Funding;Seattle Genetics: Consultancy, Honoraria, Research Funding.
ABSTRACT
COVID-19 infection has been associated with an increased incidence of thrombotic events leading to poor patient outcomes. Given the rapid rise of the COVID-19 pandemic, the ability to conduct prospective trials has been limited and data regarding the use of standard-dose versus intermediate-dose thromboprophylaxis, use of empiric therapeutic anticoagulation, and use of extended-duration thromboprophylaxis after discharge has been largely based upon observational data without any high-quality prospective data guiding their use. In this article, we will review the incidence and frequency of arterial and venous thrombotic events along with the current literature surrounding the use of intermediate-dose thromboprophylaxis, empiric therapeutic anticoagulation, and use of extended-duration thromboprophylaxis for patients hospitalized with COVID-19.