Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 19 de 19
Filter
1.
European journal of cancer (Oxford, England : 1990) ; 2022.
Article in English | EuropePMC | ID: covidwho-1877149

ABSTRACT

Importance Cancer patients have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies. Objective To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose. Methods PubMed, EMBASE, CENTRAL, and medRxiv were searched from 1 January 2021 to 10 March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist. Results After eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 haematological cancer and 82 solid cancer patients. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P≤ 0.05) and cancer type. With haematological cancer patients as a reference, lung cancer patients had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P≤ 0.05). Conclusions Administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Haematological cancer patients consistently demonstrate poorer response to booster vaccines than solid cancer patients.

2.
EJHaem ; 2022 Feb 23.
Article in English | MEDLINE | ID: covidwho-1858845

ABSTRACT

Patients with lymphoproliferative diseases are at high risk for SARS-CoV-2-related complications and mortality. The role of casirivimab and imdevimab (REGEN-COV), a neutralizing antibody cocktail, to treat immunocompromised hemato-oncological patients with SARS-CoV-2 disease 2019 (Covid-19) remains unknown. Here, we present our clinical experience on the outcome of 15 hematological patients treated with REGEN-COV for SARS-CoV-2 infection. Most patients failed to respond or achieved low antibody titer after 2-3 doses of BNT162b2 mRNA vaccine. All patients experienced clinical improvement with no mortality within a median follow-up of 70 days. In conclusion, early administration of REGEN-COV to high-risk hematological patients may prevent clinical deterioration and mortality from SARS-CoV-2 infection. The effectiveness of neutralizing antibodies may vary depending on the virus variants and in particular with the omicron variant (B.1.1.529).

3.
Antic, Darko, Milic, Natasa, Chatzikonstantinou, Thomas, Scarfò, Lydia, Otasevic, Vladimir, Rajovic, Nina, Allsup, David, Cabrero, Alejandro Alonso, Andres, Martin, Gonzales, Monica Baile, Capasso, Antonella, Collado, Rosa, Cordoba, Raul, Cuéllar-García, Carolina, Correa, Juan Gonzalo, De Paoli, Lorenzo, De Paolis, Maria Rosaria, Poeta, Giovanni Del, Dimou, Maria, Doubek, Michael, Efstathopoulou, Maria, El-Ashwah, Shaimaa, Enrico, Alicia, Espinet, Blanca, Farina, Lucia, Ferrari, Angela, Foglietta, Myriam, Lopez-Garcia, Alberto, García-Marco, José, García-Serra, Rocío, Gentile, Massimo, Gimeno, Eva, Silva, Maria Gomes, Gutwein, Odit, Hakobyan, Yervand, Herishanu, Yair, Hernández-Rivas, José Ángel, Herold, Tobias, Itchaki, Gilad, Jaksic, Ozren, Janssens, Ann, Kalashnikova, Оlga, Kalicińska, Elżbieta, Kater, Arnon, Kersting, Sabina, Koren-Michowitz, Maya, Gomez, Jorge Labrador, Lad, Deepesh, Laurenti, Luca, Fresa, Alberto, Levin, Mark-David, Bastida, Carlota Mayor, Malerba, Lara, Marasca, Roberto, Marchetti, Monia, Marquet, Juan, Mihaljevic, Biljana, Milosevic, Ivana, Mirás, Fatima, Morawska, Marta, Motta, Marina, Munir, Talha, Murru, Roberta, Nunes, Raquel, Olivieri, Jacopo, Pavlovsky, Miguel Arturo, Piskunova, Inga, Popov, Viola Maria, Quaglia, Francesca Maria, Quaresmini, Giulia, Reda, Gianluigi, Rigolin, Gian Matteo, Shrestha, Amit, Šimkovič, Martin, Smirnova, Svetlana, Špaček, Martin, Sportoletti, Paolo, Stanca, Oana, Stavroyianni, Niki, Raa, Doreen Te, Tomic, Kristina, Tonino, Sanne, Trentin, Livio, Spek, Ellen Der, Gelder, Michel, Varettoni, Marzia, Visentin, Andrea, Vitale, Candida, Vukovic, Vojin, Wasik-Szczepanek, Ewa, Wróbel, Tomasz, Segundo, Lucrecia Yáñez San, Yassin, Mohamed, Coscia, Marta, Rambaldi, Alessandro, Montserrat, Emili, Foà, Robin, Cuneo, Antonio, Carrier, Marc, Ghia, Paolo, Stamatopoulos, Kostas.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334383

ABSTRACT

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. In this retrospective multicenter study, conducted by ERIC, the European Research Initiative on CLL, we assessed the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19. Methods: : The study included patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021. Results: : A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 518 were defined as having severe COVID: 162 were admitted to the ICU while 356 received oxygen supplementation outside the ICU. Most patients (90%) were receiving thromboprophylaxis. During COVID-19 treatment, 8.8% developed a thromboembolic event, while 4.8% experienced bleeding. Thrombosis developed in 20.5% of patients who were not receiving thromboprophylaxis, but only in 8.1% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (11.1% vs. 4.2%, respectively) and in elderly. In multivariate analysis, peak D-dimer level was a poor prognostic factor for thrombosis occurrence (OR=1.020, 95%CI 1.006‒1.033), while thromboprophylaxis use was protective (OR=0.194, 95%CI 0.061‒0.614). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR=1.055, 95%CI 1.013-1.103 and OR=2.490, 95%CI 1.044-5.935, respectively). Conclusions: : Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.

5.
Clin Microbiol Infect ; 28(5): 735.e5-735.e8, 2022 May.
Article in English | MEDLINE | ID: covidwho-1693765

ABSTRACT

OBJECTIVES: The recent surge in coronavirus disease 2019 cases led to the consideration of a booster vaccine in previously vaccinated immunosuppressed individuals. However, the immunogenic effect of a third-dose severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in immunosuppressed patients is still unknown. METHODS: This was an observational cohort study of 279 previously vaccinated immunosuppressed patients followed at a single tertiary hospital in Israel. Patients were administered a third dose of the Pfizer-BioNTech mRNA vaccine (BNT162b2) between July 14 and July 21, 2021. Levels of IgG antibodies against the spike receptor-binding domain of SARS-CoV-2 were measured 3 to 4 weeks after vaccination. RESULTS: Of the cohort of 279 patients, 124 (44.4%) had haematologic malignancies, 57 (20.4%) had rheumatologic diseases, and 98 (35.1%) were solid organ-transplant recipients. Anti-SARS-CoV-2 antibody levels increased in 74.9% of cases. Across the entire cohort, the median absolute antibody levels (expressed in AU/mL) increased from 7 (interquartile range (IQR), 0.1-69) to 243 (IQR, 2-4749) after the booster dose. The response significantly varied across subgroups: The transplant cohort showed the greatest increase in absolute antibody levels (from 52 (IQR, 7.25-184.5) to 1824 (IQR, 161-9686)), followed by the rheumatology (from 22 (IQR, 1-106) to 1291 (IQR, 6-6231)) and haemato-oncology (from 1 (IQR, 0.1-7) to 7.5 (IQR, 0.1-407.5)) cohorts. The χ2 test was 8.30 for difference in fold change (p = 0.016). Of the 193 patients who were seronegative at baseline, 76 became seropositive after vaccination, corresponding to a 39.4% (95% CI, 32.8%-46.4%) seroconversion rate. Transplant patients had the highest seroconversion rate (58.3% (95% CI, 44.3%-71.2%)), followed by rheumatology (44.1% (95% CI, 28.9%-60.5%)) and haemato-oncology (29.7% (95% CI, 22%-38.8%); χ2 = 11.87; p = 0.003) patients. DISCUSSION: A third dose of BNT162b2 is immunogenic in most immunosuppressed individuals, although antibody response may differ based on the type of disease and immunosuppression. The antibody level that correlates with protection is still unknown; thus, future studies are needed to evaluate clinical outcomes.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Prospective Studies , Vaccines, Synthetic
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-308661

ABSTRACT

Purpose: Vaccine-associated hypermetabolic lymphadenopathy (VAHL) is frequently observed on [ 18 F]FDG PET-CT following BNT162b2 administration. Recent data suggest a prominent B-cell germinal-center (GC) response elicited by mRNA vaccines in draining lymph nodes. Thus, in this study we aimed to explore the correlation between VAHL and humoral immunity as reflected by post-vaccination serologic testing, and by comparing the incidence of VAHL between lymphoma patients treated recently with B-cell depleting therapy and those that did not. Methods: : A total of 137 patients with hematologic malignancy that had post-vaccination [ 18 F]FDG PET-CT were included (All-PET group), 86 received both vaccine doses before imaging (PET-2 group). Their VAHL status and grade on imaging were recorded. Among 102 lymphoma patients, 34 (33.3%) were treated during the year prior vaccination with anti-CD20 antibody containing therapy. A subgroup of 54 patients also underwent serologic testing 2-3 weeks after the booster dose, and their anti-spike titers were recorded and graded as well. Results: : The overall incidence of VAHL in patients with hematologic malignancy was 31.4%. The 34 lymphoma patients treated during the year prior vaccination with anti-CD20 antibody containing therapy had significantly lower rates of VAHL comparted to all other lymphoma patients (8.8% versus 41.2% in all-PET patients, Pv < 0.01). VAHL rates were 10% in patients with negative serology, 31.3% in patients with low anti-spike titers and 72.2% in patients with high anti-spike titers. The positive predictive values of VAHL were 90% and 93.3% in all-PET and PET-2 patients, respectively. A positive statistically significant correlation was found between VAHL and serology ranks in All-PET patients (r s = 0.530, Pv < 0.001), and stronger correlation was found in PET-2 patients (r s = 0.642, Pv < 0.001). Conclusion: VAHL on [ 18 F]FDG PET-CT of patients with hematologic malignancy may reflect GC B-cell proliferation and an effective humoral response elicited by BNT162b2 vaccine.

7.
Br J Haematol ; 196(6): 1329-1333, 2022 03.
Article in English | MEDLINE | ID: covidwho-1648446

ABSTRACT

This prospective study evaluated seroconversion rates in response to BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine booster in 44 B-cell non-Hodgkin lymphoma (B-NHL) patients who failed to respond to two prior doses [42 previously exposed to anti-CD20 monoclonal antibodies (moAbs) including 13 under maintenance treatment]. Seroconversion was obtained in 29.5% of the patients. Longer time from last anti-CD20 moAb (>6 months) and diagnosis of aggressive lymphoma compared to other, incurable B-NHLs were associated with increased seroconversion rates (47.8% vs.10.5%, p = 0.019 and 50% vs. 17.9%, p = 0.025 respectively). Thus, seronegative patients with B-NHL that completed anti-CD20 therapy more than 6 months prior to the booster have greater chances to achieve seroconversion.


Subject(s)
COVID-19 , Lymphoma, Non-Hodgkin , Vaccines , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Immunization, Secondary , Lymphoma, Non-Hodgkin/therapy , Prospective Studies , RNA, Messenger , SARS-CoV-2 , Seroconversion
8.
Blood ; 139(5): 678-685, 2022 02 03.
Article in English | MEDLINE | ID: covidwho-1551192

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to coronavirus disease 2019 (COVID-19) vaccination. Here, we evaluated the antibody response to a third BNT162b2 mRNA vaccine in patients with CLL/small lymphocytic lymphoma (SLL) who failed to achieve a humoral response after standard 2-dose vaccination regimen. Anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies were measured 3 weeks after administration of the third dose. In 172 patients with CLL, the antibody response rate was 23.8%. Response rate among actively treated patients (12.0%; n = 12/100) was lower compared with treatment-naïve patients (40.0%; n = 16/40; OR = 4.9, 95% CI 1.9-12.9; P < .001) and patients off-therapy (40.6%; n = 13/32; OR = 5.0, 95% CI 1.8-14.1; P < .001), (P < .001). In patients actively treated with Bruton's tyrosine kinase (BTK) inhibitors or venetoclax ± anti-CD20 antibody, response rates were extremely low (15.3%, n = 9/59, and 7.7%, n = 3/39, respectively). Only 1 of the 28 patients (3.6%) treated with anti-CD20 antibodies <12 months prior to vaccination responded. In a multivariate analysis, the independent variables that were associated with response included lack of active therapy (OR = 5.6, 95% CI 2.3-13.8; P < .001) and serum immunoglobulin A levels ≥80 mg/dL (OR = 5.8, 95% CI 2.1-15.9; P < .001). In patients with CLL/SLL who failed to achieve a humoral response after standard 2-dose BNT162b2 mRNA vaccination regimen, close to a quarter responded to the third dose of vaccine. The antibody response rates were lower during active treatment and in patients with a recent exposure (<12 months prior to vaccination) to anti-CD20 therapy. This trial was registered at www.clinicaltrials.gov as #NCT04862806.


Subject(s)
/therapeutic use , COVID-19/prevention & control , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Aged , Antibodies, Viral/blood , Antibodies, Viral/immunology , Antibody Formation , COVID-19/blood , COVID-19/immunology , Female , Humans , Immunity, Humoral , Leukemia, Lymphocytic, Chronic, B-Cell/blood , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Male , Middle Aged , SARS-CoV-2/immunology
9.
J Med Virol ; 2021 Nov 09.
Article in English | MEDLINE | ID: covidwho-1508794

ABSTRACT

Immunocompromised patients have an increased risk of persistent COVID-19 disease. We report here the clinical course of two patients with hematologic malignancies hospitalized due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In both patients, viral evolution including new spike gene mutations that occurred following treatment with anti-SARS-CoV-2 antibodies preparations, including convalescent plasma and bamlanivimab. These cases demonstrate the possibility of antibody-resistant SARS-CoV-2 infections evolution in immunocompromised patients.

10.
Blood ; 138(18): 1652-1653, 2021 11 04.
Article in English | MEDLINE | ID: covidwho-1501985
11.
Leukemia ; 35(12): 3444-3454, 2021 12.
Article in English | MEDLINE | ID: covidwho-1493064

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to Coronavirus disease 2019 (COVID-19) due to age, disease, and treatment-related immunosuppression. We aimed to assess risk factors of outcome and elucidate the impact of CLL-directed treatments on the course of COVID-19. We conducted a retrospective, international study, collectively including 941 patients with CLL and confirmed COVID-19. Data from the beginning of the pandemic until March 16, 2021, were collected from 91 centers. The risk factors of case fatality rate (CFR), disease severity, and overall survival (OS) were investigated. OS analysis was restricted to patients with severe COVID-19 (definition: hospitalization with need of oxygen or admission into an intensive care unit). CFR in patients with severe COVID-19 was 38.4%. OS was inferior for patients in all treatment categories compared to untreated (p < 0.001). Untreated patients had a lower risk of death (HR = 0.54, 95% CI:0.41-0.72). The risk of death was higher for older patients and those suffering from cardiac failure (HR = 1.03, 95% CI:1.02-1.04; HR = 1.79, 95% CI:1.04-3.07, respectively). Age, CLL-directed treatment, and cardiac failure were significant risk factors of OS. Untreated patients had a better chance of survival than those on treatment or recently treated.


Subject(s)
COVID-19/complications , COVID-19/mortality , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/mortality , COVID-19/diagnosis , COVID-19/virology , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Leukemia, Lymphocytic, Chronic, B-Cell/virology , Mortality , Prognosis , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Survival Analysis
13.
Cancer J ; 27(4): 328-333, 2021.
Article in English | MEDLINE | ID: covidwho-1354352

ABSTRACT

ABSTRACT: Coronavirus disease 2019 (COVID-19) has markedly impacted on the management of patients with chronic lymphocytic leukemia (CLL) and their outcome in the last year. The cumulative incidence of COVID-19 in patients with CLL in 1 year was approximately 3% in the recent Italian CAMPUS CLL survey; large retrospective studies have documented a higher mortality in patients with CLL hospitalized for severe COVID-19 compared with the general population. Controversial results for CLL-directed treatment have been reported, with some studies suggesting a potential benefit for BTK inhibitors. Reducing the number of hospital visits, delaying treatment whenever possible, and using oral therapy have become the mainstay of management in these patients. Available results with severe acute respiratory syndrome coronavirus 2 vaccines indicate an immune serological response in 40% of patients only, with a detrimental effect of recent therapy with or without anti-CD20 therapy, older age, and hypogammaglobulinemia. Further studies are needed to determine the best strategies in patients with CLL regarding (i) management of concomitant COVID-19, (ii) identification of patients in whom CLL therapy can be safely postponed, (iii) CLL treatment algorithms, and (iv) optimal severe acute respiratory syndrome coronavirus 2 vaccination strategies.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , COVID-19 Vaccines , Humans , Protein Kinase Inhibitors/therapeutic use
14.
Roeker, Lindsey E.; Scarfo, Lydia, Chatzikonstantinou, Thomas, Abrisqueta, Pau, Eyre, Toby A.; Cordoba, Raul, Muntañola Prat, Ana, Villacampa, Guillermo, Leslie, Lori A.; Koropsak, Michael, Quaresmini, Giulia, Allan, John N.; Furman, Richard R.; Bhavsar, Erica B.; Pagel, John M.; Hernandez-Rivas, Jose Angel, Patel, Krish, Motta, Marina, Bailey, Neil, Miras, Fatima, Lamanna, Nicole, Alonso, Rosalia, Osorio-Prendes, Santiago, Vitale, Candida, Kamdar, Manali, Baltasar, Patricia, Österborg, Anders, Hanson, Lotta, Baile, Mónica, Rodríguez-Hernández, Ines, Valenciano, Susana, Popov, Viola Maria, Barez Garcia, Abelardo, Alfayate, Ana, Oliveira, Ana C.; Eichhorst, Barbara, Quaglia, Francesca M.; Reda, Gianluigi, Lopez Jimenez, Javier, Varettoni, Marzia, Marchetti, Monia, Romero, Pilar, Riaza Grau, Rosalía, Munir, Talha, Zabalza, Amaya, Janssens, Ann, Niemann, Carsten U.; Perini, Guilherme Fleury, Delgado, Julio, Yanez San Segundo, Lucrecia, Gómez Roncero, Ma Isabel, Wilson, Matthew, Patten, Piers, Marasca, Roberto, Iyengar, Sunil, Seddon, Amanda, Torres, Ana, Ferrari, Angela, Cuéllar-García, Carolina, Wojenski, Daniel, El-Sharkawi, Dima, Itchaki, Gilad, Parry, Helen, Mateos-Mazón, Juan José, Martinez-Calle, Nicolas, Ma, Shuo, Naya, Daniel, Van Der Spek, Ellen, Seymour, Erlene K.; Gimeno Vázquez, Eva, Rigolin, Gian Matteo, Mauro, Francesca Romana, Walter, Harriet S.; Labrador, Jorge, De Paoli, Lorenzo, Laurenti, Luca, Ruiz, Elena, Levin, Mark-David, Šimkovič, Martin, Špaček, Martin, Andreu, Rafa, Walewska, Renata, Perez-Gonzalez, Sonia, Sundaram, Suchitra, Wiestner, Adrian, Cuesta, Amalia, Broom, Angus, Kater, Arnon P.; Muiña, Begoña, Velasquez, César A.; Ujjani, Chaitra S.; Seri, Cristina, Antic, Darko, Bron, Dominique, Vandenberghe, Elisabeth, Chong, Elise A.; Lista, Enrico, García, Fiz Campoy, Del Poeta, Giovanni, Ahn, Inhye, Pu, Jeffrey J.; Brown, Jennifer R.; Soler Campos, Juan Alfonso, Malerba, Lara, Trentin, Livio, Orsucci, Lorella, Farina, Lucia, Villalon, Lucia, Vidal, Maria Jesus, Sanchez, Maria Jose, Terol, Maria Jose, De Paolis, Maria Rosaria, Gentile, Massimo, Davids, Matthew S.; Shadman, Mazyar, Yassin, Mohamed A.; Foglietta, Myriam, Jaksic, Ozren, Sportoletti, Paolo, Barr, Paul M.; Ramos, Rafael, Santiago, Raquel, Ruchlemer, Rosa, Kersting, Sabina, Huntington, Scott F.; Herold, Tobias, Herishanu, Yair, Thompson, Meghan C.; Lebowitz, Sonia, Ryan, Christine, Jacobs, Ryan W.; Portell, Craig A.; Isaac, Krista, Rambaldi, Alessandro, Nabhan, Chadi, Brander, Danielle M.; Montserrat, Emili, Rossi, Giuseppe, Garcia-Marco, Jose A.; Coscia, Marta, Malakhov, Nikita, Fernandez-Escalada, Noemi, Skånland, Sigrid Strand, Coombs, Callie C.; Ghione, Paola, Schuster, Stephen J.; Foà, Robin, Cuneo, Antonio, Bosch, Francesc, Stamatopoulos, Kostas, Ghia, Paolo, Mato, Anthony R.; Patel, Meera.
Blood ; 136(Supplement 1):45-49, 2020.
Article in English | PMC | ID: covidwho-1338959

ABSTRACT

Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020;Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects.Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts.CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. <6), CLL treatment history, details regarding COVID-19 course, management, and therapy, and vital status were collected.The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies;univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx).Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98);31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2).Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L;27% vs. 21%), and lymphocytopenia (ALC <1.0 x 109/L;18% vs. 28%), while others varied between Co1 and Co2 (p<0.0001), including cough (61% vs. 93%), dyspnea (60% vs. 84%), fatigue (13% vs. 77%).Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p<0.0001). Figure 1 depicts OS in each cohort. Univariable analyses demonstrated that age and CIRS ≥6 significantly predicted inferior OS in both cohorts, while only age remained an independent predictor of inferior OS in multivariable analyses (Table 2). Prior treatment for CLL (vs. observation) predicted inferior OS in Co1 but not Co2.Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including thera eutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts;COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented.

15.
Br J Haematol ; 195(2): 186-193, 2021 10.
Article in English | MEDLINE | ID: covidwho-1289897

ABSTRACT

Multiple myeloma (MM) patients are at excess risk for clinically significant COVID19 infection. BNT162b2 mRNA COVID19 (BNT162b2) vaccine provides effective protection against COVID19 for the general population, yet its effect in MM patients may be compromised due to disease and therapy-related factors and was not yet evaluated. This single-centre prospective study included MM patients tested for serological response 14-21 days post second vaccine. Vaccinated healthy volunteers served as controls. In all, 171 MM patients, median age 70 (38-94) were included; 159 active MM and 12 smouldering myeloma (SMM). Seropositive response rate (median titer) was 76% (91 U/ml) in active MM patients vs 98% (992 U/ml) in the 64 controls (P < 0·0001), and 100% (822 U/ml) in SMM patients. Multivariate analysis revealed older age (P = 0·009), exposure to ≥4 novel anti-myeloma drugs (P = 0·02) and hypogammaglobulinaemia (P = 0·002) were associated with lower response rates. None of the novel agents significantly decreased response rate, whereas daratumumab trended towards reduced response (P = 0·08). Adverse events occurred in 53% and 55% of the MM patients and controls, respectively, all transient grade 1-2. In conclusion, BNT162b2 vaccine was safe and provided a high seropositivity rate in MM patients, independent of treatment type. Older, hypogammaglobulinaemic and heavily pretreated patients had lower response rates.


Subject(s)
/adverse effects , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Immunity, Humoral/immunology , Multiple Myeloma/immunology , Adult , Agammaglobulinemia/complications , Aged , Aged, 80 and over , Antibodies, Monoclonal/adverse effects , /immunology , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Case-Control Studies , Female , Humans , Immunity, Humoral/drug effects , Male , Middle Aged , Multiple Myeloma/complications , Multiple Myeloma/diagnosis , Multivariate Analysis , Predictive Value of Tests , Prospective Studies , Risk Factors , SARS-CoV-2/genetics , Treatment Outcome
16.
Patient Prefer Adherence ; 15: 945-952, 2021.
Article in English | MEDLINE | ID: covidwho-1234620

ABSTRACT

OBJECTIVE: Hemato-oncology patients are at high risk for morbidity and mortality from coronavirus disease (COVID-19). The resultant heightened anxiety among these patients may negatively affect adherence to therapy and treatment-related outcome. We aimed to assess whether the adoption of precautionary measures provided by the medical team led to a reduction in COVID-19-related anxiety and, consequently, to successful execution of treatment plans. METHODS: All adult hemato-oncology patients actively treated or being followed-up at the outpatient service at Tel Aviv Sourasky Medical Center between March 25 and May 3, 2020, were invited to answer a questionnaire that focused on their anxiety and adherence to treatment following new measures to reduce risk of infection during the first COVID-19 outbreak. RESULTS: One hundred and fifty patients (representing 24% of those being approached), average age 67 years, 52% male, and 57% undergoing antineoplastic therapy, responded to the survey. The introduction of precautionary measures resulted in a significant reduction in anxiety level in all patients, irrespective of age, sex, or treatment status. Attendance to scheduled visits in day care and outpatient clinics remained unchanged. Adherence to planned blood and imaging tests were 81% and 73%, respectively, and 93% of the patients were satisfied with their medical care. Thirty-two percent of patients used telemedicine. Satisfaction with telemedicine was highest among non-actively treated patients and those experiencing high anxiety levels. CONCLUSION: Reorganization of the hemato-oncology unit and provision of information to patients reduced COVID-19-related anxiety and enabled the same delivery of therapy as that prior to the pandemic.

17.
Eur J Nucl Med Mol Imaging ; 48(11): 3540-3549, 2021 10.
Article in English | MEDLINE | ID: covidwho-1219108

ABSTRACT

PURPOSE: Vaccine-associated hypermetabolic lymphadenopathy (VAHL) is frequently observed on [18F]FDG PET-CT following BNT162b2 administration. Recent data suggest a prominent B cell germinal-center (GC) response elicited by mRNA vaccines in draining lymph nodes. Thus, in this study we aimed to explore the correlation between VAHL and humoral immunity as reflected by post-vaccination serologic testing and by comparing the incidence of VAHL between lymphoma patients treated recently with B cell depleting therapy and those that were not. METHODS: A total of 137 patients with hematologic malignancy that had post-vaccination [18F]FDG PET-CT were included (All-PET group), 86 received both vaccine doses before imaging (PET-2 group). Their VAHL status and grade on imaging were recorded. Among 102 lymphoma patients, 34 (33.3%) were treated during the year prior vaccination with anti-CD20 antibody containing therapy. A subgroup of 54 patients also underwent serologic testing 2-3 weeks after the booster dose, and their anti-spike titers were recorded and graded as well. RESULTS: The overall incidence of VAHL in patients with hematologic malignancy was 31.4%. The 34 lymphoma patients treated during the year prior vaccination with anti-CD20 antibody containing therapy had significantly lower rates of VAHL comparted with all other lymphoma patients (8.8 versus 41.2% in all-PET patients, Pv < 0.01). VAHL rates were 10% in patients with negative serology, 31.3% in patients with low anti-spike titers, and 72.2% in patients with high anti-spike titers. The positive predictive values of VAHL were 90 and 93.3% in all-PET and PET-2 patients, respectively. A positive statistically significant correlation was found between VAHL and serology ranks in All-PET patients (rs = 0.530, Pv < 0.001), and stronger correlation was found in PET-2 patients (rs = 0.642, Pv < 0.001). CONCLUSION: VAHL on [18F]FDG PET-CT of patients with hematologic malignancy may reflect GC B cell proliferation and an effective humoral response elicited by BNT162b2 vaccine.


Subject(s)
COVID-19 , Hematologic Neoplasms , Lymphadenopathy , COVID-19 Vaccines , Humans , Immunity, Humoral , Lymphadenopathy/diagnostic imaging , Positron Emission Tomography Computed Tomography , RNA, Messenger , SARS-CoV-2
18.
Blood ; 137(23): 3165-3173, 2021 06 10.
Article in English | MEDLINE | ID: covidwho-1190021

ABSTRACT

Patients with chronic lymphocytic leukemia (CLL) have an increased risk for severe COVID-19 disease and mortality. The goal of this study was to determine the efficacy of COVID-19 vaccine in patients with CLL. We evaluated humoral immune responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine in patients with CLL and compared responses with those obtained in age-matched healthy control subjects. Patients received 2 vaccine doses, 21 days apart, and antibody titers were measured by using the Elecsys Anti-SARS-CoV-2 S assay after administration of the second dose. In a total of 167 patients with CLL, the antibody response rate was 39.5%. A comparison between 52 patients with CLL and 52 sex- and aged-matched healthy control subjects revealed a significantly reduced response rate among patients (52% vs 100%, respectively; adjusted odds ratio, 0.010; 95% confidence interval, 0.001-0.162; P < .001). The response rate was highest in patients who obtained clinical remission after treatment (79.2%), followed by 55.2% in treatment-naive patients and 16.0% in patients under treatment at the time of vaccination. In patients treated with either Bruton's tyrosine kinase inhibitors or venetoclax ± anti-CD20 antibody, response rates were considerably low (16.0% and 13.6%). None of the patients exposed to anti-CD20 antibodies <12 months before vaccination responded. In a multivariate analysis, the independent predictors of response were younger age, female sex, lack of currently active treatment, immunoglobulin G levels ≥550 mg/dL, and immunoglobulin M levels ≥40 mg/dL. In conclusion, antibody-mediated response to the BNT162b2 mRNA COVID-19 vaccine in patients with CLL is markedly impaired and affected by disease activity and treatment. This trial was registered at www.clinicaltrials.gov as #NCT04746092.


Subject(s)
COVID-19 , Leukemia, Lymphocytic, Chronic, B-Cell , Aged , COVID-19 Vaccines , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/genetics , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , RNA, Messenger/genetics , SARS-CoV-2
19.
Leukemia ; 34(9): 2354-2363, 2020 09.
Article in English | MEDLINE | ID: covidwho-638239

ABSTRACT

Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 [95% CI 1.79-7.71]). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.


Subject(s)
Betacoronavirus , Coronavirus Infections/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Pneumonia, Viral/pathology , Adenine/analogs & derivatives , Age Factors , Aged , Aged, 80 and over , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , COVID-19 , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Male , Middle Aged , Pandemics , Piperidines , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Prognosis , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/pharmacology , Pyrazoles/therapeutic use , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Surveys and Questionnaires
SELECTION OF CITATIONS
SEARCH DETAIL