COVID-19 mRNA Vaccine in Patients With Lymphoid Malignancy or Anti-CD20 Antibody Therapy: A Systematic Review and Meta-Analysis

Ito, Yusuke; Honda, Akira; Kurokawa, Mineo

doi:10.1016/j.clml.2022.03.012

Cited by 8 publications

(11 citation statements)

References 149 publications

(310 reference statements)

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“…Gagelmann et al included data on 1564 patients from 13 studies and showed a pooled antibody response of 76% (95% CI: 67–83%) with significant heterogeneity (I² = 91%) [ 33 ]. The results were consistent with the meta-analysis by Ito et al, who performed a subgroup analysis on 15 studies with data on MM and found a pooled seropositivity rate of 78% (95% CI: 69%-86%) with significant heterogeneity (I² = 92%) [ 111 ]. Expectedly, patients with smoldering MM (SMM; 5 studies), similarly as presumed for MGUS patients, showed a high pooled seroconversion rate of 94% (95% CI: 76–100%; I² = 87%), which was not statistically different from healthy individuals (random effects RR 0.96, 95% CI: 0.75–1.24) [ 111 ].…”

Section: Methodssupporting

confidence: 89%

“…Several studies have evaluated the immune response following the prime complete COVID-19 vaccination in patients with MM [ 68 , 71 – 110 ]. Three large meta-analyses have summarized the findings of these studies [ 32 , 33 , 111 ]. Gagelmann et al included data on 1564 patients from 13 studies and showed a pooled antibody response of 76% (95% CI: 67–83%) with significant heterogeneity (I² = 91%) [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

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Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

et al. 2023

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In the post-pandemic COVID-19 period, human activities have returned to normal and COVID-19 cases are usually mild. However, patients with multiple myeloma (MM) present an increased risk for breakthrough infections and severe COVID-19 outcomes, including hospitalization and death. The European Myeloma Network has provided an expert consensus to guide patient management in this era. Vaccination with variant-specific booster vaccines, such as the bivalent vaccine for the ancestral Wuhan strain and the Omicron BA.4/5 strains, is essential as novel strains emerge and become dominant in the community. Boosters should be administered every 6–12 months after the last vaccine shot or documented COVID-19 infection (hybrid immunity). Booster shots seem to overcome the negative effect of anti-CD38 monoclonal antibodies on humoral responses; however, anti-BCMA treatment remains an adverse predictive factor for humoral immune response. Evaluation of the immune response after vaccination may identify a particularly vulnerable subset of patients who may need additional boosters, prophylactic therapies and prevention measures. Pre-exposure prophylaxis with tixagevimab/cilgavimab is not effective against the new dominant variants and thus is no longer recommended. Oral antivirals (nirmatrelvir/ritonavir and molnupiravir) and remdesivir are effective against Omicron subvariants BA.2.12.1, BA.4, BA.5, BQ.1.1 and/or XBB.1.5 and should be administered in MM patients at the time of a positive COVID-19 test or within 5 days post symptoms onset. Convalescent plasma seems to have low value in the post-pandemic era. Prevention measures during SARS-CoV-2 outbreaks, including mask wearing and avoiding crowded places, seem prudent to continue for MM patients.

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Section: Methodssupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

et al. 2023

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“…All five patients in our trial who were diagnosed with lymphoma and underwent CD20 B-cell depletion therapy following prime-boost vaccination presented with a median titer of 1235 AU/mL in treatment follow-up. Other authors recently outlined that while anti-CD20 therapy worsens response rates to prime-boost vaccines when given prior to vaccination, already established antibody responses were attenuated but sustained in those patients starting treatment after COVID-19 vaccination [ 58 , 59 ]. Hence, clinicians should weigh the necessity of an instant start to cancer treatment against the application of booster vaccinations beforehand.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

Krekeler

Reitnauer

Bacher

et al. 2022

Cancers

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Background: Two-dose COVID-19 vaccination often results in poor humoral response rates in patients with hematologic malignancies (HMs); yet responses to COVID-19 booster vaccines and the risk of COVID-19 infection post-booster are mostly uncertain. Methods: We included 200 outpatients with HMs and predominantly lymphoid neoplasms (96%, 191/200) in our academic center and reported on the humoral responses, which were assessed by measurement of anti-spike IgG antibodies in peripheral blood as early as 14 days after mRNA-based prime-boost vaccination, as well as factors hampering booster efficacy. Previous basic (double) immunization was applied according to the local recommendations with mRNA- and/or vector-based vaccines. We also report on post-booster COVID-19 breakthrough infections that emerged in the Omicron era and the prophylaxis strategies that were applied to poor and non-responders to booster vaccines. Results: A total of 55% (110/200) of the patients achieved seroconversion (i.e., anti-spike protein IgG antibody titer > 100 AU/mL assessed in median 48 days after prime-boost vaccination) after prime-boost vaccination. Multivariable analyses revealed age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion to be independent predictors for booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% (p < 0.001) and serum–antibody titer (S-AbT) levels increased by 90 AU/mL (p = 0.011). Notably, obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab (p = 0.002). Of poor or non-responders to prime-boost vaccination, 41% (47/114) underwent a second booster and 73% (83/114) underwent passive immunization. COVID-19 breakthrough infections were observed in 15% (29/200) of patients after prime-boost vaccination with predominantly mild courses (93%). Next to seroconversion, passive immunization was associated with a significantly lower risk of COVID-19 breakthrough infections after booster, even in vaccine non-responders (all p < 0.05). In a small proportion of analyzed patients with myeloid neoplasms (9/200), the seroconversion rate was higher compared to those with lymphoid ones (78% vs. 54%, accordingly), while the incidence rate of COVID-19 breakthrough infections was similar (22% vs. 14%, respectively). Following the low frequency of myeloid neoplasms in this study, the results may not be automatically applied to a larger cohort. Conclusions: Patients with HMs are at a high risk of COVID-19 booster vaccine failure; yet COVID-19 breakthrough infections after prime-boost vaccination are predominantly mild. Booster failure can likely be overcome by passive immunization, thereby providing immune protection against COVID-19 and attenuating the severity of COVID-19 courses. Further sophistication of clinical algorithms for preventing post-vaccination COVID-19 breakthrough infections is urgently needed.

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“…By title/abstract screening, 188 articles were identified for fulltext view. Finally, 18 systematic reviews (15 with meta-analyses and 3 without meta-analyses) were identified which fulfilled the eligibility criteria (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). The study flow was depicted according to the PRISMA guidelines in Figure 2.…”

Section: Search Resultsmentioning

confidence: 99%

“…Five articles focused on the lymphoma, the vaccine responses were over 50.00% (52.00 to 60.00%), except one first dose result was 16.30%. Gagelmann et al ( 20 ) and Ito et al ( 26 ) reported the vaccine response in Hodgkin's lymphoma, aggressive non-Hodgkin's lymphoma and indolent non-Hodgkin's lymphoma. The results were 91.00 and 95.00% (RR = 0.95) in Hodgkin's lymphoma, 58.00 and 58.00% (RR = 0.60) in aggressive non-Hodgkin's lymphoma, 61.00 and 52.00% (RR = 0.54) in indolent non-Hodgkin's lymphoma.…”

Section: Resultsmentioning

confidence: 99%

COVID-19 vaccine response and safety in patients with cancer: An overview of systematic reviews

Sun

et al. 2022

Front. Public Health

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BackgroundTo date, the COVID-19 pandemic does not appear to be overcome with new variants continuously emerging. The vaccination against COVID-19 has been the trend, but there are multiple systematic reviews on COVID-19 vaccines in patients with cancer, resulting in redundant and sub-optimal systematic reviews. There are still some doubts about efficacy and safety of the COVID-19 vaccine in cancer patients.PurposeTo identify, summarize and synthesize the available evidence of systematic reviews on response and COVID-19 vaccine safety in patients with cancer.MethodsMultiple databases were searched from their inception to May 1, 2022 to fetch the relevant articles. Study quality was assessed by AMSTAR2. The protocol of this study was registered on PROSPERO (CRD42022327931).ResultsA total of 18 articles were finally included. The seroconversion rates after first dose were ranged from 37.30–54.20% in all cancers, 49.60–62.00% in solid cancers and 33.30–56.00% in hematological malignancies. The seroconversion rates after second dose were ranged from 65.30–87.70% in all cancers, 91.60–96.00% in solid cancers and 58.00–72.60% in hematological malignancies. Cancer types and types of therapy could influence vaccine response. COVID-19 vaccines were safe and well–tolerated.ConclusionsThis study suggests COVID-19 vaccine response is significantly lower in cancer patients. Number of received doses, cancer types and treatment strategies could influence response of COVID-19 vaccine in cancer patients. COVID-19 vaccines are safe and well–tolerated. Considering the emergence of several new variants of SARS-CoV-2 with potential influence on ongoing vaccination programs, there is a need for booster doses to increase the effectiveness of COVID-19 vaccines.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022327931, identifier CRD42022327931.

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COVID-19 mRNA Vaccine in Patients With Lymphoid Malignancy or Anti-CD20 Antibody Therapy: A Systematic Review and Meta-Analysis

Cited by 8 publications

References 149 publications

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

Management of patients with multiple myeloma and COVID-19 in the post pandemic era: a consensus paper from the European Myeloma Network (EMN)

Efficacy of COVID-19 Booster Vaccines in Patients with Hematologic Malignancies: Experiences in a Real-World Scenario

COVID-19 vaccine response and safety in patients with cancer: An overview of systematic reviews

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