scholarly journals Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma

2021 ◽  
Vol 5 (16) ◽  
pp. 3053-3061
Author(s):  
C. Perry ◽  
E. Luttwak ◽  
R. Balaban ◽  
G. Shefer ◽  
M. M. Morales ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Messenger Rna ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Response Rates ◽  
Serological Response ◽  
Healthy Controls ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Abstract Patients diagnosed with B-cell non-Hodgkin lymphoma (B-NHL), particularly if recently treated with anti-CD20 antibodies, are at risk of severe COVID-19 disease. Because studies evaluating humoral response to COVID-19 vaccine in these patients are lacking, recommendations regarding vaccination strategy remain unclear. The humoral immune response to BNT162b2 messenger RNA (mRNA) COVID-19 vaccine was evaluated in patients with B-NHL who received 2 vaccine doses 21 days apart and compared with the response in healthy controls. Antibody titer, measured by the Elecsys Anti-SARS-CoV-2S assay, was evaluated 2 to 3 weeks after the second vaccine dose. Patients with B-NHL (n = 149), aggressive B-NHL (a-B-NHL; 47%), or indolent B-NHL (i-B-NHL; 53%) were evaluated. Twenty-eight (19%) were treatment naïve, 37% were actively treated with a rituximab/obinutuzumab (R/Obi)–based induction regimen or R/Obi maintenance, and 44% had last been treated with R/Obi >6 months before vaccination. A seropositive response was achieved in 89%, 7.3%, and 66.7%, respectively, with response rates of 49% in patients with B-NHL vs 98.5% in 65 healthy controls (P < .001). Multivariate analysis revealed that longer time since exposure to R/Obi and absolute lymphocyte count ≥0.9 × 103/μL predicted a positive serological response. Median time to achieve positive serology among anti-CD20 antibody-treated patients was longer in i-B-NHL vs a-B-NHL. The humoral response to BNT162b2 mRNA COVID-19 vaccine is impaired in patients with B-NHL who are undergoing R/Obi treatment. Longer time since exposure to R/Obi is associated with improved response rates to the COVID-19 vaccine. This study is registered at www.clinicaltrials.gov as #NCT04746092.

scholarly journals CD20 antibodies: type II to tango?

Blood ◽  
2012 ◽  
Vol 119 (22) ◽  
pp. 5061-5063 ◽  
Author(s):  
Marinus H. J. van Oers
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Type Ii ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20 ◽  
Intense Research ◽  
Cd20 Antibodies

Although the chimeric anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell non-Hodgkin lymphoma (NHL), still many patients relapse and an increasing number become refractory to rituximab-containing therapy. This has initiated intense research to develop more potent anti-CD20 antibodies.

scholarly journals Bispecific Antibodies: A Review of Development, Clinical Efficacy and Toxicity in B-Cell Lymphomas

2021 ◽  
Vol 11 (5) ◽  
pp. 355
Author(s):  
Ross Salvaris ◽  
Jeremy Ong ◽  
Gareth P. Gregory
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Treated Patient ◽  
Progression Free Survival ◽  
Response Rates ◽  
Bispecific Antibodies ◽  
B Cell Lymphomas ◽  
T Cell Therapy ◽  
Effector Cells ◽  
Non Hodgkin Lymphoma

The treatment landscape of B-cell lymphomas is evolving with the advent of novel agents including immune and cellular therapies. Bispecific antibodies (bsAbs) are molecules that recognise two different antigens and are used to engage effector cells, such as T-cells, to kill malignant B-cells. Several bispecific antibodies have entered early phase clinical development since the approval of the CD19/CD3 bispecific antibody, blinatumomab, for relapsed/refractory acute lymphoblastic leukaemia. Novel bsAbs include CD20/CD3 antibodies that are being investigated in both aggressive and indolent non-Hodgkin lymphoma with encouraging overall response rates including complete remissions. These results are seen even in heavily pre-treated patient populations such as those who have relapsed after chimeric antigen receptor T-cell therapy. Potential toxicities include cytokine release syndrome, neurotoxicity and tumour flare, with a number of strategies existing to mitigate these risks. Here, we review the development of bsAbs, their mechanism of action and the different types of bsAbs and how they differ in structure. We will present the currently available data from clinical trials regarding response rates, progression free survival and outcomes across a range of non-Hodgkin lymphoma subtypes. Finally, we will discuss the key toxicities of bsAbs, their rates and management of these adverse events.

Immunogenicity of Influenza Vaccination in Patients with Non-Hodgkin Lymphoma: Final Report after Two Epidemic Seasons.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4598-4598
Author(s):  
Piotr Centkowski ◽  
Lidia B. Brydak ◽  
Magdalena Machala ◽  
Ewa Kalinka ◽  
Maria Blasinska-Morawiec ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Hodgkin Lymphoma ◽  
Geometric Mean ◽  
Humoral Response ◽  
Final Report ◽  
Healthy Controls ◽  
Serum Samples ◽  
Non Hodgkin Lymphoma ◽  
Antibody Titers

Abstract Vaccination against influenza is recommended for immunocompromised individuals. However, there is little information concerning the efficacy of vaccination in patients (pts) with non-Hodgkin lymphoma (NHL). The purpose of this study was to assess humoral response to standard intramuscular trivalent subunit influenza vaccine in pts with NHL as compared to healthy subjects. In two consecutive epidemic seasons, 2003/2004 and 2004/2005, 163 pts and 92 healthy controls were vaccinated. Antibody titers to hemagglutinin (HA) and neuraminidase (NA) were measured in serum samples collected before vaccination, and 1 and 6 months apart. Changes in the hemagglutination inhibition (HAI) and neuraminidase inhibition (NII) antibody titers were assessed by comparing geometric mean titers and mean fold increases to baseline values and by comparing changes in the HA seroconversion and seroprotection rates. Pts who received influenza vaccine during 2003/2004 season had after one month increases in the geometric mean titers by a factor of 8,64–26,60 for HI and 6,93–12,66 for NI, as compared with respective increases by a factor of 9,12–24,41 and 4,83–10,31 for the healthy controls. At one month after vaccination seroprotection and seroresponse rates were similar in the two groups, ranging from 68,42 to 84,21 % and 71,93 to 94,74 % in NHL and 66,67–82,22 % and 62,22–86,67 % in controls, respectively. After six months, seroprotection and seroresponse rates had decreased in NHL group to 31,91–38,30% and 46,81–72,34%, respectively. Pts who received influenza vaccine during 2004/2005 season had after 1 month increases in the geometric mean titers by a factor of 38,76–41,49 for HI and 26,59–30,31 for NI, as compared with respective increases by a factor of 81,19–104,32 and 52,16–54,52 for the healthy controls. Seroprotection and seroresponse rates were lower in the former group, ranging from 62,11 to 65,26 % and 74,47 to 77,66 %, respectively. After six months, these parameters had decreased to 24,72–31,46% and 57,30–59,55%, respectively. In both studied seasons, pts achieved titres of functional antibodies greater than the protective threshold, irrespective of the previous chemotherapy administration. The results of this study indicate that standard influenza vaccination induces sufficient immune responses in pts with NHL. Previous chemotherapy adminstration seems to have no impact on the efficacy of vaccination.

A phase I trial of ublituximab (TG-1101), a novel glycoengineered anti-CD20 monoclonal antibody (mAb) in B-cell non-Hodgkin lymphoma patients with prior exposure to rituximab.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 8524-8524 ◽  
Author(s):  
Owen A. O'Connor ◽  
Changchun Deng ◽  
Jennifer Effie Amengual ◽  
Mazen Y. Khalil ◽  
Marshall T. Schreeder ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Phase I ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase I Trial ◽  
Prior Exposure ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

scholarly journals Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients

2021 ◽  
Author(s):  
Catherine Diefenbach ◽  
Jessica Caro ◽  
Akiko Koide ◽  
Michael Grossbard ◽  
Judith Goldberg ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Neutralizing Antibodies ◽  
Close Contact ◽  
Humoral Response ◽  
Hematologic Malignancies ◽  
Igg Antibody ◽  
Neutralization Capacity ◽  
Non Hodgkin Lymphoma ◽  
Current Guidance ◽  
Anti Cd20

Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti- CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.

scholarly journals Efficacy of a Third BNT162b2 mRNA COVID-19 Vaccine Dose in Patients with CLL who Failed Standard Two-dose Vaccination

Blood ◽  
2021 ◽  
Author(s):  
Yair Herishanu ◽  
Galia Rahav ◽  
Shai Levi ◽  
Andrei Braester ◽  
Gilad Itchaki ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Response Rate ◽  
Vaccine Dose ◽  
Humoral Response ◽  
Response Rates ◽  
Lymphocytic Leukemia ◽  
Vaccination Regimen ◽  
The Third ◽  
Anti Cd20

Patients with chronic lymphocytic leukemia (CLL) have an impaired antibody response to 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 two-dose vaccination regimen. Anti-SARS-CoV-2S and neutralizing 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 to treatment-naïve patients (40.0%, n=16/40; OR=4.9, 95% CI 1.9-12.9; p&lt;0.001) and patients off-therapy (40.6%, n=13/32; OR=5.0, 95% CI 1.8-14.1; p&lt;0.001), (p&lt;0.001). In those actively treated with 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 one of the 28 patients (3.6%) treated with anti-CD20 antibodies &lt;12 months prior to vaccination responded. The anti-SARS-CoV-2S antibody levels correlated linearly with neutralizing antibody titers (r=0.732, p&lt;0.001). 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&lt;0.001) and serum IgA levels ≥80 mg/dL (OR=5.8, 95% CI 2.1-15.9; p&lt;0.001) In conclusion, in patients with CLL/SLL who failed to achieve a humoral response after standard two-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 (&lt;12 months prior to vaccination) to anti-CD20 therapy.

scholarly journals Efficacy of the BNT162b2 mRNA COVID-19 Vaccine in Patients with Chronic Lymphocytic Leukemia: A Serologic and Cellular Study

Chemotherapy ◽  
2021 ◽  
Author(s):  
Stefano Molica ◽  
Diana Giannarelli ◽  
Mirella Lentini ◽  
Daniela Zappala ◽  
Ada Mannella ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Antibody Response ◽  
Messenger Rna ◽  
Vaccine Dose ◽  
Lymphocytic Leukemia ◽  
Serological Response ◽  
Humoral Immune ◽  
Treatment Naïve ◽  
Cd20 Antibody ◽  
Anti Cd20

Background: Antibody response following SARS-CoV2 vaccination is somewhat defective in chronic lymphocytic leukemia (CLL). Moreover, the correlation between serologic response and status of cellular immunity has been poorly studied. Objective: This study was undertaken to assess humoral immune and cellular responses to the BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in CLL. Methods: The presence of the spike antibodies was assessed at a median time of 14 days from the second vaccine dose of SARS-CoV2 in 70 CLL followed-up at a single institution. Results: The antibody response rate (RR) in CLL patients was 58.5%, compared to 100% of 57 healthy controls of the same sex and age (P< 0.0001). Patients treatment-naïve and those in sustained clinical remission after therapy had the highest RR (87.0% and 87.7%, respectively). In contrast, patients on therapy with a pathway inhibitor as monotherapy and those treated with an association of anti-CD20 antibody were unlikely to respond to the SARS-CoV-2 vaccine (52% and 10%, respectively). In multivariate analysis, early Rai stage (OR, 0.19 [0.05-0.79]; P=0.02) and no previous therapy (OR, 0.06[0.02-0.27]; P<0.0001) were found to be independent predictors of vaccination response. An increase in absolute NK cells (i.e., CD16/CD56 positive cells) in patients with a serological response was found following the second dose of vaccine (P=0.02). Conclusions: These results confirm that serological response to the BNT162b2 vaccine in patients with CLL is impaired. A third boosting vaccine dosage should be considered for these patients.

scholarly journals Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy

2021 ◽  
Author(s):  
Matthias B. Moor ◽  
Franziska Suter-Riniker ◽  
Michael P. Horn ◽  
Daniel Aeberli ◽  
Jennifer Amsler ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Vaccine Dose ◽  
Lymphocyte Subpopulation ◽  
University Hospital ◽  
Healthy Controls ◽  
Vaccine Response ◽  
Treatment History ◽  
History Of ◽  
Anti Cd20

Background B-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation. Methods Patients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by IFN-g release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29). Results Anti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-g; release was detected in 17% of patients and 86% of healthy controls (p<0.001). Only 5% of patients, but 86% of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/ul), and CD4+ lymphocyte count (>653/ul) predicted humoral vaccine response (area under the curve [AUC]: 62% [CI 56-78], 67% [CI 58-80] and 67% [CI 54-79], (positive predictive value [PPV]: 0.76, 0.7 and 0.71). Conclusion This study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

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