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

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.

Increasing insight in the value of repetitive COVID‐19 vaccination in patients with haematological malignancies in the Omicron era

“…Strikingly, all patients who had received rituximab within 6 months before the COVID-19 failed to produce anti-N and anti-S antibodies. The latter was in line with our own study 5 encompassing 200 patients in Germany with haematological malignancies (96% with lymphoid neoplasms) who received COVID-19 booster vaccines. We examined the impact of time interval (<3, 3-12, >12 months) between last cancer treatment and third vaccination on seroconversion rates and antibody titre levels in the anti-CD20 treated group and compared the results with the remaining non-anti-CD20-treated patients (e.g.…”

Benefit of repeatedCOVID‐19 vaccination for patients with B‐cell malignancies

“…We could show that with each month between B‐cell depletion and booster vaccination, the probability of seroconversion increased by approximately 4% ( p < 0.001) and serum−antibody titre levels were significantly increasing, too. This finding supports the correlation between serologic response and COVID‐19 vaccinations post‐second dose observed in the study of Pinder et al 4 Interestingly, B‐cell depletion with obinutuzumab was associated with an 85% lower probability for seroconversion after prime‐boost vaccination as compared to rituximab ( p = 0.002) in our study 7 . This demonstrates that different compounds with anti‐B‐cell activity and potential of B‐cell depletion may impact differently on the success of COVID‐19 vaccination.…”

“…Recently, we investigated 200 patients with hematologic malignancies, of those 96% with lymphoid neoplasms. 7 Seroconversion after the first booster vaccination was documented in 55% of patients. Higher age, lymphocytopenia, ongoing treatment and prior anti-CD20 B-cell depletion were independent predictors of booster failure.…”

“…This finding supports the correlation between serologic response and COVID-19 vaccinations post-second dose observed in the study of Pinder et al 4 Interestingly, B-cell depletion with obinutuzumab was associated with an 85% lower probability for seroconversion after prime-boost vaccination as compared to rituximab (p = 0.002) in our study. 7 This demonstrates that different compounds with anti-B-cell activity and potential of B-cell depletion may impact differently on the success of COVID-19 vaccination.…”

“…Other factors had as well be found to be relevant to achieve sufficient anti‐spike IgG antibody titres. Recently, we investigated 200 patients with hematologic malignancies, of those 96% with lymphoid neoplasms 7 . Seroconversion after the first booster vaccination was documented in 55% of patients.…”