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

SIMPLE SUMMARY: The current study provides data on the efficacy of COVID-19 prime-boost vaccines in 200 patients with hematologic and predominantly lymphoid malignancies as well as a risk-adapted guidance for the management of weak and failed responses to COVID-19 prime-boost vaccination. A total of...

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Detalles Bibliográficos
Autores principales: Krekeler, Carolin, Reitnauer, Lea, Bacher, Ulrike, Khandanpour, Cyrus, Steger, Leander, Boeckel, Göran Ramin, Klosner, Justine, Tepasse, Phil-Robin, Kemper, Marcel, Hennies, Marc Tim, Mesters, Rolf, Stelljes, Matthias, Schmitz, Norbert, Kerkhoff, Andrea, Schliemann, Christoph, Mikesch, Jan-Henrik, Schmidt, Nicole, Lenz, Georg, Bleckmann, Annalen, Shumilov, Evgenii
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9688056/
https://www.ncbi.nlm.nih.gov/pubmed/36428605
http://dx.doi.org/10.3390/cancers14225512
Descripción
Sumario:SIMPLE SUMMARY: The current study provides data on the efficacy of COVID-19 prime-boost vaccines in 200 patients with hematologic and predominantly lymphoid malignancies as well as a risk-adapted guidance for the management of weak and failed responses to COVID-19 prime-boost vaccination. A total of 55% of the patients achieved seroconversion after a prime-boost vaccination. Age, lymphocytopenia, ongoing treatment and anti-CD20 B-cell depletion were independent predictors of booster failure. With each month between anti-CD20-mediated B-cell depletion and booster vaccine, the probability of seroconversion increased by 4% and serum–antibody titer levels increased by 90 AU/mL. Obinutuzumab treatment was associated with an 85% lower probability for seroconversion after prime-boost vaccination compared to rituximab. Of poor and non-responders to a prime-boost vaccine, 41% underwent a second booster vaccination and 73% underwent pre-emptive passive immunization. COVID-19 breakthrough infections were documented in only 15% patients with predominantly mild courses (93%). Next to seroconversion after prime-boost vaccination, passive immunization significantly reduced the risk of COVID-19 breakthrough infections during follow-up. ABSTRACT: 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.